Over the years, research have shown of that several heavy metals are ubiquitously prevalent in the ecosystem, which are of global concern as a result of to their deleterious effects on human health ( Briffa et al., 2020). Although, many heavy metals, such as copper (Cu), manganese (Mn), iron (Fe), and zinc (Zn), are essential for normal cellular performance, these metals, however, can also be toxic to the human body when present in excess of the normal concentration ( Jomova et al., 2022) Literature has revealed a few popular heavy metals which have shown to cause vicious health effects. Moreso, distinguishing and varying attributes have also been described a plethora of literature ( Meharg and Meharg, 2021; Mishra et al., 2019: Charkiewicz et al., 2023; Baig et al., 2024a; Baig et al., 2024b).

Lead is eccentrically the oldest popularly known and the most surplus heavy metal pollutant/contaminant ( Sable et al., 2024) and it is unsusceptible to corrosion under brassy environmental conditions while being easily transformed into various forms at room temperature ( Rihan et al., 2020). Over the years, lead has been widely used in gasoline (Collin et al., 2022), paint ( Charkiewicz and Backstrand, 2020), water pipelines ( Levin et al., 2021), and batteries ( Kumar et al., 2022), in the production of cooking utensils ( Kuhangana et al., 2024) construction materials ( Dong et al., 2023) and the toy industry ( Yazdanfar et al., 2022). As a result of this, the primary sources of lead exposure have been from the atmosphere ( Wu et al., 2022), water ( Charkiewicz and Backstrand, 2020), food and drinking water ( Gump et al., 2020), contaminated soil and dust ( Stanek et al., 2020) or lead-containing consumer products, especially vintage items ( Guney et al., 2020) and flaking peeling paints ( Afolayan et al., 2021). Also, mercury has been reported in research as a key component of dental amalgam, and arsenic-containing compounds have also been reported being used for chemotherapeutic and insecticidal purposes ( Khatun et al., 2022; Genchi et al., 2020b). Also, mecury and arsenic take part in microbial methylation mechanisms in their inorganic forms which involves the addition of a methyl group to the toxic moiety to form a less toxic, but mainly water-soluble and easily absorbed, methylated compound ( Byeon et al., 2021). Precisely, chronic release of inorganic mercury or other organic moieties in the air to disrupt motor and sensory functions leads to the emergence of Minamata disease ( Niede and Benbi, 2022). In the same vein, subtly, arsenic-laden underground water bombards cereals and tubers to develop a mild form of neurotoxicity in contaminated areas due to long-term arsenic exposure ( Sevak and Pushkar, 2024), Methylmercury (Me-Hg) in seafood, particularly in pregnant mothers’ diet, has been implicated to sparks off neurobehavioral symptoms during early development ( Wu et al., 2024), and fish and seafood likely account for 90% of Hg exposure in people residing near rivers and lakes ( Vergara et al., 2024). Furthermore, Cadmium is a highly toxic non-essential element used in electroplating, the television industry, battery production, and coating agents of iron and steel products ( Sable et al., 2024). The major route of human exposure of cadmium is via the ingestion of polluted food, such as rice, shellfish and vegetables ( Zhao et al., 2023) or through inhalation of tobacco smoke ( Genchi et al., 2020b). Alarminly, a huge proportion of cigarettes are haphazardly intermittently irrigated with cadmium fertilizers, which may subsequently release the heavy metal (cadmium) from tobacco during smoking

In recent years, widespread human exposure to heavy metals has fascinated increasing public awareness to the probable threat to public health ( Qureshi, 2021). Lead (Pb) has much long been reported by researchers and medical experts to have baleful effects on human health ( Wang et al., 2022b). The major sources of lead exposure are environmental lead pollution ( Raj and Das, 2023). Particularly, there is no safe portal for lead exposure, and the toxicological profile of lead is influenced by the age at exposure, sex ( Gade et al., 2021) and genetic polymorphism ( Sekovanić et al., 2020). Furthermore, lead pollution is an environment-related global health concern, recognized as a public health issue by several global organizations ( WHO, 2023; Muzamil et al., 2024; Słota et al., 2022; Obeng-Gyasi, 2019).

Metallic lead is relatively unreactive under many conditions ( Liu et al., 2021). When heated or subjected to moist air, it can be oxidized and form a variety of inorganic and organic lead compounds, which can further decompose into other lead materials, such as organo-lead and alkyllead ( Nielsen, 2020). Inorganic and organic lead are the two main species linked with detrimental human health effects ( Borah et al., 2020). Due to the long-term presence of lead, in the atmosphere, soil, and water, the exposure of the global population to lead inevitably results in pollution of resources and impacts on the biota ( Mousavi, et al., 2022). Occupational exposures have long been closely associated with painters who use paints containing lead pigments and workers exposed to smoke from burning fuels containing added organic halogenated lead ( Wei et al., 2022; Thangavel et al., 2022). In addition to providing extensive exposure to lead, anthropogenic activities have been reported to trigger environmental spills, such as zinc-lead and copper-silver deposits in the Mississippi valley ( Rosa et al., 2023). The introduction of Tetraethyl lead (TEL) into gasoline supplies also contributed to significant environmental pollution, with large-scale human exposure ( Sarkar, 2020). Lead has also been reported to be released from smelters, recycling centers in municipal areas ( Du et al., 2020) and young ones have been lead-exposed by previously used sources of drinking water ( Olufemi et al., 2022). However, lifestyle choices such as smoking and the use of lead-containing diet fillings have been reported as other means of human exposure to lead. Also research has shown that use of beauty products such as cosmetic products facial creams ( Rico et al., 2023) and surfactants containing lead-based chemicals can result in direct lead toxicity without consuming them ( Abed et al., 2023).

Furthermore, in developing countries, increasing occurrences of lead poisoning have been reported and linked to informal or unregulated electronic waste (e-waste) management practices resulting in severe environmental contamination ( Gollakota et al., 2020) Through various exposure routes (ingestion, inhalation and dermal exposure), lead pollutants threaten human health ( Natasha et al., 2020). Particularly In humans, lead can trigger impacts widely, and these harmful effects are persistent ( Briffa et al., 2020), hence, long-term lead accumulated in the body can increase the gravity of the toxic effects with advancing age. Research have shown that lead exposure to humans can affect the following systems negatively; pulmonary ( Wei et al., 2020), bone ( Boskabady et al., 2022), hepatic and renal systems ( Satarug et al., 2020) neurologic ( Eiró et al., 2021) cognitive and behaviour system ( Shvachiy et al., 2020). Over the years, lead exposure have been reported in a plethora of articles to cause anemia in many individuals ( Wang et al., 2021; Mukisa et al., 2020; Kaneko et al., 2020 ) particularly children being susceptible to the neurotoxic effects ( Brittenham et al., 2023) Some of the weighty consequences of chronic exposure are arthritis ( Fang et al., 2023) and chronic kidney disease that may lead to renal dysfunction ( Balali-Mood et al., 2021). Considering its plausible worrisome effects on the wellbeing of humans and the ecosystem lead exposure is very much a major public health concern globally ( WHO, 2023).

Mercury contamination is amongst the most significant and universal pollution problems in the aquatic environment ( Gupta and Yadav, 2024) It primarily occurs in the aquatic environment ( Luo et al., 2020). In industries, huge amounts of effluents containing mercury are discharged as a result of poor industrial operations (pharmaceutical, paint, paper, and other industries), fertilizer industry, landfill leaching, and carbon combustion. Dead zones, otherwise termed as zones of oxygen-depleted water, have been reported to be the repository of huge deposits of inorganic mercury ( AlgarnI et al., 2023; Jonidi Jafari et al., 2020).

The mercury in the environment rapidly makes its entry into aquatic biota. The mercury is consecutively transported to the aquatic food chain via bioaccumulation ( Saidon et al., 2024). Aquatic diet have been reported to contain a huge amount of mercury ( Barone et al., 2021) which puts the concept of food from the aquatic environment in doubt. The widespread presence of mercury contaminated fish in all types of water bodies has grave effects on the global aquatic environment, economy, and public health ( Abhishek et al., 2022). Therefore, it imperative to fathom the coaction between mercury content in fish and the source of water, fish size, and type of species, well-known poisoning effects, extreme intolerance effects, and treatments. Hence, this review will provide an unbiased interpretation of the effects of heavy metal mercury on global health and the aquatic environment.

Cadmium (Cd) is toxic, nonessential, and carcinogenic for humans and animals ( Genchi et al., 2020b). Cadmium exposure to the environment is primarily due to anthropogenic activities ( Zhao et al., 2023; Knoell and Wyatt, 2021; Adil et al., 2020), just like every other heavy metals and not much of natural sources exist. Cadmium have been reported to be present in tobacco products , particularly cigarettes ( Dinh et al., 2021). Also, cadmium is also present in foods, such as shellfish, rice, mushrooms, drinking water, spinach, and other green leafy vegetables ( Genchi et al., 2020b), with rice being one of the major routes of exposure via food. Major sources of cadmium pollution are nonferrous smelters ( Wei et al., 2022), industrial production involving cadmium ( Suhani et al., 2021), incineration of municipal waste and sewage sludges Król et al., 2022). Research have shown that bio- transfer is the common way for the entry of cadmium into the food web ( Peana et al., 2022; Sun et al., 2020) Cadmium is taken up by the plants and also accumulates in the soil ( Sterckeman and Thomine, 2020), it is also easily ignored in the environment for a longer time due to its chemical nature and releases gradually unlike other metals. Also, cadmium takes a longer time to degrade in the environment due to its long biological half-life ( Genchi et al., 2020a).

Human exposure to high-level of cadmium have been reported in a plethora of research to leading to severe damage to the liver, kidneys, and lungs ( Satarug, 2012; Branca et al., 2020; Knoell and Wyatt, 2021; Chandravanshi, et al., 2021; Owonikoko et al., 2023; Farh et al., 2024). Also, lots of animal studies have shown neurotoxic effects as a result of cadmium exposure ( Branca et al., 2020; Zhou et al., 2020; Gade et al., 2021; Ruczaj and Brzóska, 2023; Patel et al., 2021) Clinical symptoms such as headaches ( Söderholm et al., 2020), osteoarthritis ( Frangos and Maret, 2020; Xia et al., 2022) dizziness ( Dumpala et al., 2024), cough ( Li et al., 2020 ), bronchitis ( Ibrahimou et al., 2021), and fever has been reported via research to be associated with cadmium exposure ( Elmas, 2023) Furthermore, plausible bone damages have been reported to be caused by cadmium exposure ( Ma et al., 2022). Also, research as also emphasized in recent years that low-level chronic cadmium may also lead to kidney damage ( Tsai et al., 2021), which primarily focuses on the degree of damage observed in the process of β2-microglobulin excretion and α-glutathione-S-transferase in the urine of human ( Polaka et al., 2023). A recent study has revealed that cadmium-induced renal tubulointerstitial injury might ultimately lead to decreased functionality ( Xu et al., 2021) Also a plethora of research have revealed that environmental that environmental exposure to cadmium also causes endocrine and hormone-disrupting effects ( Rai et al., 2019; Li and Li, 2020; Di Ciaula and Nazarian et al., 2024; Yang et al., 2024). A recent study have also revealed that cadmium exposure in humans through inhalation may induce lung cancer ( Lee and Lee, 2024) and cadmium ingestion through tobacco has been reported to cause oral cancer ( Satir, 2022). In addition, environmental cadmium may be associated with primary liver cancer ( Cirovic and Satarug, 2024) Research has also revealed that children exposed to cadmium via dietary intake exhibit lower intelligence than those not exposed ( Kampouri et al., 2024).

Arsenic is a metalloid which is naturally present lithosphere ( Meharg and Meharg, 2021). It enters the environment either due to anthropogenic usage or through removal from iron, manganese, and aluminum oxides ( Raju, 2022). Several anthropogenic sources, such as mining activities, smelting, and burning of fossil fuels, release arsenic into the environment ( Kar, 2022). Chronic or acute exposure to arsenic have been reported to cause debilitating health effects ( Thankachan et al., 2023 Muzaffar et al., 2023; Rehman et al., 2020). Organo-arsenic compounds dominate arsenic exposure, but these compounds have been reported to transform into inorganic forms and hence more toxic forms in the body ( Valskys et al., 2022). Groundwater is the primary source of arsenic exposure ( Monteiro De Oliveira et al., 2021), about 21 countries have been found to contain arsenic-ridden drinking water ( WHO, 2022).

Chronic exposure to arsenic-rich drinking water may lead to the development of skin lesions ( Rajiv et al., 2023; WHO, 2022), internal cancers of the blood vessels ( Rahaman et al., 2021) or urinary bladders among others ( Jaafarzadeh et al., 2023). This phenomenon have been reflected in a plethora of studies ( Mayer and Goldman, 2016; Kumar and Ghosh, 2019; Rahaman et al., 2021; Kumar et al., 2022; Rehman et al., 2020; Chikkanna et al., 2019). Cadmium has been implicated in several biological pathways to cause carcinogenesis ( Peana et al., 2022; Zhu and Costa, 2020; Cui et al., 2021; Luparello, 2021) including oxidative stress ( Branca et al., 2020). mitochondrial DNA damage and apoptosis ( Mohamed, 2022) impairment of DNA methylation ( Genchi et al., 2020b), and changes in methyltransferases ( Sun et al., 2021). Moreso, It is acute arsenic exposure can lead to systemic poisoning and ultimately death ( Ganie et al., 2024). A single lethal dose of arsenic compounds ranges between 100 to 200 mg ( Chen et al., 2021). Symptoms of acute poisoning include diarrhea, poor appetite, extreme tiredness, sores on the skin, numbness, muscle cramps and hair loss ( Rehberg and Rehberg, 2024) However, acute poisonings from waterborne arsenic exposure are uncommon ( Roy and Edwards, 2022). Long-term skin exposure may cause skin changes, such as darkening of the skin ( Passeron et al., 2020) and the appearance of small “corns” or “warts” on the palms soles, and body ( Hamza et al., 2022). Also, research studies have revealed plausible effects of arsenic exposure on reproductive health and impaired fetal brain development ( Dutta et al., 2022).

The avenues through which humans come into contact with heavy metals vary greatly between different contaminants and among different populations. Ingestion represents the main route of exposure for most human population groups ( Kabir et al., 2022). Affected individuals generally include those living close to contaminated areas , those accidentally exposed to pollutants and occupationally-exposed individuals . Inhalation ( Briffa et al., 2020) and, to a lesser extent, dermal contact may also represent more relevant exposure routes for special populations, such as workers engaged in mining smelting ( Xu et al., 2021; Li et al., 2020) or in the production and application of herbicides, pesticides, and fertilizers . Human exposure to heavy metals includes, at least, ten different interconnected exposure pathways. These pathways include affected food and drinking water resources and lead to the wide distribution of hazardous heavy metals in the tissues, organs, and fluids of the human body ( Zhao et al., 2022). Taken together, human intake of heavy metals is driven by lifestyle local environment ( Mitra et al., 2022) occupation ( Baig et al., 2024b), nutrition and the occurrence and concentration of heavy metals in affected air, water, and soil resources ( Fu and Xi, 2020).

Ingestion represents the major pathway of human exposure to heavy metals . A number of food sources contain considerable levels of heavy metals, such as crops grown in heavy metals-contaminated soils ( Bwatanglang et al., 2022) fish from mercury-contaminated waters and beverages containing lead carried by deteriorated distribution systems. Human dietary intake typically ranges from approximately 0.1 to 1.0 g/day, with higher intake levels observed in diets rich in seafood and other wild foods. Overall, high daily intakes and the evidence from research suggest that moderate to high levels of heavy metal residues in food and water can trigger significant toxicological effects in humans ( Ahmad et al., 2021).

a. Ingestion

The major medium for human exposure to toxic metals is ingestion ( Dippong et al., 2024). This is facilitated by the consumption of micro- or macro-nutrients and subsequent accumulation of metals in human food, water, air, or soil ( Kara et al., 2024). An acute part usually comes from water used for gardening or agriculture ( Munir et al., 2021). Stationary plants take up toxic metals from the soil and enrich the water table, this water is used for cultivating terrestrial and aqueous food as well ( Zheng et al., 2023; Chaturvedi et al., 2021; Wicke et al., 2021). Research have shown that children are particularly susceptible to soil contamination due to hand-to-mouth activities and due to their low body mass ( Karatela et al., 2020) and potential for higher ingestion of air, water, and food in comparison to adults on a body weight basis ( Frings et al., 2024; Ahmad et al., 2021). During pregnancy, the narrow teenaged pelvis tends to concentrate nutrients and lead into mothers’ bone thickness ( Haeusler et al., 2021) calcium is rapidly pulled out during menopause. The lead stored in the bones may cause fetal wastage, fertility decrements, and low birth weight (Collin et al., 2022). Exposure via this route may result in poor breathing and hence directly absorbed through cell membranes of the lung ( Khoshakhlagh et al., 2024). Water can also be very high in toxic metals and hence be detrimental to the consumer ( Briffa et al., 2020). Food grown near or processed with such commodities from contaminated water will also result in toxic ingestion ( Yüksel et al., 2023 ). The taste of water is important to determine when water becomes unfit for human consumption; therefore, heavy metals in solution or in a state of suspension can be ingested through water as drinking water or through food and is vital to prevent water and food pollution ( Mazinder Baruah and Singh, 2022; Sonone et al., 2020). Fish rearing in polluted soil, nitrogenized ponds take up metals via food and gill; hence fish as a food can affect the public and should not be cooked and fed to children ( Porretti et al., 2022). Fish is a good indicator for bioaccumulation of metals ( Sheikhzadeh and Hamidian, 2021; Pironti et al., 2021).

b. Inhalation

Humans are predominantly exposed to toxic heavy metals from a plethora of industries in the surroundings ( Singh et al., 2023). Inhalation happens as a result of direct exposure; as a result, it is one of the most hazardous routes ( Yasmeen and Hafeez, 2023; Sonwani et al., 2021; Kurt and Basaran, 2020). The heavy metals are present both in particles and in fumes ( Hedberg et al., 2021; Sonwani et al., 2021). Inhalation of particles is more common, although heavy metals are excreted from the system as they are insoluble in water. Heavy metal inhalation have been reported to cause a plethora of disorders that exert their effects on numerous body systems ( Fulke et al., 2024). Even if the systemic manifestations are not noticeable at the outset, the disease will ultimately harm other systems, ( Abd Elnabi et al., 2023) particularly the central nervous system . Approximately 95% of inhaled lead particles are 1-2 μm in diameter and therefore do not eliminate easily and persist in the body for a long time. Respiratory disturbances can be induced by long-term or higher-lead exposure ( Dumková et al., 2020). Airborne free cadmium have shown to produce hazardous effects by the respiratory system ( Bhattacharyya et al., 2023); conversely, its oxide and chloride have been reported to have no effect ( Genchi et al., 2020a). Moreso, exposure to a higher level of cadmium have been reported via literature to cause inflammation and emphysema ( Wang et al., 2024). Also, there is strong evidence from literature that heavy metal have impacted workers; revealing nickel refinery workers have been reported to have more nasal and nasal-chronic disorders than non-impacted workers ( Kurt and Basaran, 2020; Syurin and Vinnikov, 2022). Cadmium sulfate and smoker’s cadmium have been revealed to be deleterious to the upper respiratory pathways ( Genchi et al., 2020b).

c. Dermal contact

Heavy metals are a growing threat to general public health and exhibit known toxic impacts on humans and the environment ( Mitra et al., 2022) Nowadays, heavy metals are scattered in every nook and cranny of the environment ( Adeola, 2020; Kumar et al., 2023). The circulation of heavy metals occurs through the air, water, and food cycle, with plants representing the primary source ( Sonone et al., 2020). Nonetheless exposure to heavy metals can also be via the skin. The dermal surface area in adults varies from 1.5 to 2 m ², whereas in children, the ratio of skin surface area to body weight is higher ( Zhao et al., 2023). Hence, children are at a higher risk of exposure to heavy metals in the environment compared to adults ( Zheng et al., 2023). Even dust on the floor of houses and soil can cause health problems when inhaled or ingested with food ( Roy et al., 2024). The uptake of heavy metals, either through respiration or via the skin, now creates debilitating health hazards ( Edo et al., 2024; Passeron et al., 2020). To determine the significance of dermal contact as a route of human exposure to toxic metals, it is imperative to fathom that wherever required, metal ions must be mobilized from the surface of a contaminant particle that contacts human skin. However, toxic metals are normally present in an oxidized or insoluble state in natural environmental particles ( Saravanan et al., 2022).

Heavy metals exert their toxic effects in a highly complex process with thorough mechanisms which are yet to be understood ( Mitra et al., 2022; Engwa et al., 2019). However, several direct mechanisms have been proven to be involved in exerting the deleterious effects of heavy metals including oxidative stress DNA damage ( Fu and XI, 2020), membrane damage quenching of in vivo antioxidants ( Pisoschi et al., 2021), protein dysfunction and enzyme inactivation ( Balali-Mood et al., 2021).

In an effort to elucidate the mechanisms of metal toxicity, Shi et al. (2004) reported that via oxidative stress, heavy metals were able to form complexes with biological molecules such as lipids, proteins, and DNA, which lead to cell injury by generating or regulating the content of reactive oxygen species (ROS) effects ( Acharya, 2024; Fasae and Abolaji, 2022). Reduced antioxidant status effects and dysregulation of antioxidant enzymes have been reported to decrease antioxidant status effects and allow formation of free radicals, thus cumulative body injury ( García-Sánchez et al., 2020). Metallic oxides are able to reduce cytochromes and to generate active oxygen species this can further result in cellular levels of adsorption and the resultant genomic deoxyribonucleic acid (DNA) methylation ( Mitra et al., 2022). All of the aforementioned mechanisms may gradually results into carcinogenesis. A review by Adil et al. (2020) heavy metals in various cells were able to induce changes in signal transduction pathways, thus alterations in gene expression, DNA repair organelles, cause inflammation, and genotoxic stress. All these changes ultimately lead to carcinogenesis. One highly prominent DNA modifying mechanism that is thought to occur is the generation of ROS. In addition to ROS generation, metals have also been found to have a direct effect on DNA via the formation of metal-DNA adducts where a single base pair is displaced and metal ions then sit in the space created ( Marchi, 2023).

a. Oxidative stress

The human body has a conglomerate of elements such as heavy metals that perform numerous functions in the body ( Mitra et al., 2022: Some metals are essential for the homeostasis of the organisms (REF). while some are toxic when they overly interact and get supplemented in the cells (REF). A plethora of heavy metals such as lead, mercury, arsenic, and cadmium have no specified physiological function ( Balali-Mood et al., 2021). Above that, they disrupt numerous enzymatic processes happening inside the body ( Muzaffar et al., 2023). The generation of reactive oxygen species (ROS) is noticeable by metals, concerning oxidative stress that ultimately leads to imbalances between the body’s antioxidant defense mechanisms and prooxidants ( Afzal et al., 2023). In recent years, extensive heavy metal poisoning cases have been reported in a plethora of research ( Guo et al., 2020; Hu et al., 2020; Obasi and Akudinobi, 2020). Hence, it has become an imperative area of research to investigate the source and remediation of heavy metals. Oxidative stress is an unpleasant condition created by the buildup of free radicals or any mismatch between the production of free radicals and application of antioxidants ( Marchi 2023; Martemucci et al., 2022). Many pathological and psychological disorders have been reported to have been caused by oxidative stress in the human body ( Kowalczyk et al., 2021). It can further spur up numerous acute or chronic diseases ( Wood et al., 2021). If the balance between the formation of free radicals and the ability of cells to survive against a redox any of an abnormality in the production of antioxidants surpasses the free radicals, oxidative stress will occur ( Chaudhary et al., 2023). In the cells of humans oxidative stress gives rise to the formation of free radical products that are life-threatening to the physiology of the cell ( Zahra et al., 2017). Heavy metal toxicity can directly be linked with oxidative stress, either by redox-cycling or by deactivation of antioxidant systems ( Nowicka, 2022). Antioxidants act as a natural defense system and neutralize excessive production of oxidants in the body due to any plausible agents ( Pisoschi et al., 2021).

b. DNA damage

Over the years, several studies, including in vitro and in vivo studies, have shown the direct and indirect genotoxic and cytogenetic effects of several metals ( Sánchez-Alarcón et al., 2021). Damage of DNA can be caused by metals such as Ni, NiO, and NiSO4 ( Genchi et al., 2020a). DNA damage have been investigated in irradiated and non-irradiated cells/nickel-containing solution, revealing he results of this study showed that DNA strand breaks, induced by nickel-titanium (NiTi) and pure nickel under the presence of ultraviolet light caused the result of the synergy between the UV light and the nickel ( Umaña et al., 2024). The mechanism(s) leading to nicking of DNA by nickel is not yet fully understood in the scientific world understood, but studies have shown that nickel binding to chromatin can affect the structure of the DNA and greatly increase susceptibility to strand scission by stripping the histone proteins from the chromatin ( Kasprzak, 2023; Sekovanić et al., 2020).

Heavy metal-induced DNA damage is a serious risk factor for many human health issues, including cancer ( Paithankar et al., 2021), aging ( Vielee and Wise JP Jr ., 2023), and neurodegenerative diseases ( Stoccoro and Coppedè, 2024). The damaging effect of exposure to metal ions and other nonessential metals on DNA has been investigated in many in vitro and in vivo studies ( Ren et al., 2024; Kasprzak, 2023; Fasae and Abolaji, 2022; Slobodian et al., 2021; Peana et al., 2021). The negative effects of heavy metals on genetic material occur mainly at four major levels: cytotoxic, genotoxic, mutagenic, and carcinogenic, depending on the exposure dose, duration, and concentration ( Dutta and Ruden, 2024; Stoccoro and Coppedè, 2024; Mitra et al., 2022).

c. Protein dysfunction

Changes in protein expression and phosphorylation have been reported in several tissues after exposure to heavy metals ( Mondal, 2023; Mansoor et al., 2023; Renu et al., 2021; Fu and Xi et al., 2020). The human body has several classes of proteins, including enzymes with well-conserved active sites, transmembrane proteins, signal transduction proteins, or transporters that heavy metals may bind to, disrupting their function ( Riziotis and Thornton, 2022). Consequently, heavy metal-binding proteins may not be released from the transporter or receptor, forming a new entity that may continuously send signal transduction, resulting in persistent acute or chronic contamination, e.g. lead intoxication , Furthermore, some proteins have been reported to be sensitive to heavy metals ( Pillai et al., 2020). Although, the effect that heavy metals have on proteins is not always very much clear but there may be a catalytic role for the heavy metals, for example Cd have been reported to collapse the structure of the hemoglobin tetramer, leading to the release of free alpha plus Cd and beta chains ( Pillai et al., 2020).

Furthermore, cadmium have been implicated to affect the enzymatic function of several proteins, including kinases, transcription factors, and metalloprotease ( Mondal, 2023). Chronic exposure of patients (humans) to cadmium (i.e., Cd-induced itai-itai disease) has been reported by medical experts ( Dutta et al., 2022; Sakurai et al., 2023) and sporadically accelerating breakdown of postmenopausal women bone by inhibiting the function of matrix metalloproteases, which stimulates bone formation and thus exacerbates the hypercalciuretic effect on the body ( Ciosek et al., 2023 Rastgar et al., 2022). Also, lead exposure have shown to cause causes amino acid substitution and increased expression of heavy metal-responsive proteins, accompanied by the induction of heme oxygenase-1 ( Kapoor et al., 2021; Haeusler et al. 2021).

The deleterious effects observed by the effects of heavy metals may be in the form of neurodevelopmental disorders like autism ( Błażewicz and Grabrucker, 2022) and attention deficit/hyperactivity disorders ( Gu et al., 2024). Medical experts have reported cognitive impairments in patients and seizures as a result of heavy metal contamination (Singh and Sharma). Along with these, changes in the level of some neurotransmitters like acetylcholine, noradrenaline, and dopamine in humans as a result of heavy metal accumulation ( Pyatha et al., 2023). Hence, suggesting that neurotoxicity has a huge health effect which should be considered at heavy metal-contaminated sites ( Baig et al., 2024b). Also, Heavy metals are known to act as neurotoxicants to all age groups of humans ( Gade et al., 2021). Exposure to heavy metals during pregnancy have been reported to result into various neurodevelopmental disorders in children ( Ijomone et al., 2020; Heng et al., 2022; Ding et al., 2023; Farmani et al., 2024; Nehzomi and Shirani, 2024). The cognitive functions of exposed children have been reported to be pathetic ( Ding et al., 2023). Lead has been implicated to cause as a result of exposure in children ( Parithathvi et al., 2024). About 1 in 100 children has autism of people have been diagnosed with autism ( Nehzomi and Shirani, 2024; WHO, 2023). A study shows that children with autism spectrum disorder have lifted harbors of various heavy metals-small molecular weight proteins such as zinc and copper ( Błażewicz and Grabrucker, 2022). In recent literature, mercury, lead, arsenic and cadmium have emerged as the two most common heavy metals linked to attention deficit hyper activity disorder (ADHD) in recent literature ( Dutta et al., 2022). The deficiency in zinc in the body of the individual is responsible. Noradrenergic and dopaminergic dysfunction have also been reported in heavy metal neurotoxicity ( Medda et al., 2020). Other forms of toxicity reported via literature in terms of prolonged exposure, is a decrease in the level of acetylcholine, which leads to cognitive and behavioral alterations ( Althobaiti, 2024). Apart from all of these, effects like Parkinsonism, depression and anxiety have also been reported in recent studies ( Mitra et al., 2022; Vellingiri et al., 2022; Baig et al., 2024a; Tizabi et al., 2024). The presence of genotoxicity on neurological systems of patients on exposure to heavy metals has also been reported via literature ( Stoccoro and Coppedè, 2024). Taken together, neurotoxicity is basically one of the important endpoints for site assessment and clean-up goals, and immediate action should be taken to prevent heavy metal exposure.

Animal studies of heavy metals have revealed cardiovascular effects ( Sonone et al., 2020; Mitra et al., 2022). This strongly indicates an association between heavy metals and the development of hypertension or hypertension-induced end-organ damage. Cadmium is the most widely studied heavy metal with respect to cardiovascular toxicity ( Garai et al., 2021). Experimental studies suggest that Cd in a general population is associated with atherosclerosis or peripheral arterial disease ( Barregard et al., 2021). Also, lead has been implicated in numerous processes associated with cellular stimulation leading to atherosclerotic plaque formation ( Libby, 2021), as well as affecting the integrity of blood vessel walls through neurotoxic and cardiotoxic effects ( Rajpoot et al., 2024). The mechanism that shows the effects of another heavy metal, arsenic, on cardiovascular health is yet to be understood. In a study that included some Bangladesh’s rural community members as well as individuals from a more general (urban as well as rural) health center, the authors reported an exposure-response relation between arthritis and heavy metal exposure, particularly for inorganic arsenic ( Choi et al., 2011). Taken together, evidence suggests that agricultural tasks can inadvertently lead to the uptake of high levels of heavy metals and that these heavy metals may act in a discriminatory nature, targeting the meninges and/or dopaminergic system, culminating in Parkinson’s disease.

Reproductive structures are very much imperative not only for existence of an individual but also for growth, enlargement and multiplication ( Massányi et al., 2020). The response of reproductive organs to toxic substances differs from that of other target organs, and they may serve as an ideal measurement for the deleterious effects of environmental contamination on animal and human health ( Massányi et al., 2020). Heavy metal exposure can cause a plethora of deleterious effects on the reproductive region of human health ( Fulke et al., 2024). Heavy metals can cause sperm DNA damage and lower sperm quality, thus affecting male fertility ( López-Botella et al., 2021) Heavy metals can also disturb sex steroid hormone levels and types of semen, resulting in subfertility ( Bhardwaj et al., 2021). On the other hand, lead, cadmium, and mercury can damage the ovaries of females who are then further at the risk of giving birth to anatomically or neurologically malformed offspring because of heavy metal-induced prenatal effects ( Yan et al., 2023). During the entire process of maturation of sperm, the cells are exposed to generated reactive oxygen species. This excessive exposure can lead to oxidative stress resulting in sperm DNA damage ( Gautam et al., 2024), which can be one of the reasons for making sperm immobile. Lead has been reported in literature to disrupt sex steroid homeostasis in human circulation ( Kasten-Jolly and Lawrence, 2017). Lower levels of luteinizing hormone, progesterone, and 17OH-progesterone have been linked with an increase in cadmium accumulation in testes and seminal plasma of infertile and asthenospermic men ( Obasi et al., 2022). Also, research as shown that once copper gets absorbed into the systemic circulation, it temporarily disrupts spermatozoa production, maturation, and hormonal homeostasis ( Bhardwaj et al., 2021). Meta-analysis evidence has revealed that the epididymis is very much sensitive to heavy metal contamination ( Machado-Neves, 2022). Furthermore, lead and cadmium are endocrine disruptors that harm the male and female reproductive system, thereby disturbing the fertility of humans. Cadmium for example was reported by Machado-Neves (2022) to be deleterious to the epididymis, leading reduction in the weight of the epidermis and reducing the number of sperms. Moreso, aluminum has also been implicated cause reduction in blood level of FSH and LH ( Ojoghoro et al., 2021), therefore affecting male fertility ( Ali et al., 2024; Di Ciaula and Portincasa, 2021). Similarly in females, heavy metals can cause negative effects in the female reproductive tracts, a recent study by Tian et al. (2024) revealed that lead is highly linked to diminished ovarian reserve at during the reproductive age of females. A plethora of research over the years have implicated cadmium in the reduction of ovaries in females ( Nna et al., 2017; Nasiadek et al., 2019; Massányi et al., 2020; Ruslee et al., 2020). Exposure to lead and transfer of lead across the placenta may cause miscarriage in females and subfertility ( Dutta et al., 2022). An increased spontaneous abortion rate as a result of lead poisoning has also been reported in animals ( Mosaad et al., 2024). Therefore, essential to assess the reproductive health of females areas in the environment likely to be contaminated with heavy metals.

Itai-itai disease is the most popular case of cadmium (Cd) pollution reported in Japan ( Sasaki et al., 2024). The term "itai-itai" is from a Japanese word which means “it hurts, it hurts” in English vocabulary ( Kaji, 2015). Around 1500 people had severe symptoms such as liver damage, osteomalacia, and bone deformities during the initial phase of the outbreak. Mostly women were the victims, and the male to female ratio of the patients was 1:2 or 1:3 ( Kasuya, 2000) Furthermore, The damage it caused in the Jinzu River basin (Japan) and surrounding areas in Toyama Prefecture was recorded by Kozukue as early as 1981. It was reported that the cause of the itai-itai disease was huge ingestion of rice. Much higher cadmium levels were found in the rice which was consumed by patients than by people living in the non-polluted areas ( Kasuya, 2000).

The main clinical symptoms were osteomalacia, renal dysfunctions, and pathological fractures. It was also reported that there were single cases of lung and prostatic cancers among the patients ( Zhang et al., 2023). The cases of chemical-induced itai-itai patients, especially, showed severe osteomalacia manifested in similar deformities of the elbow, femoral neck, and knee.

In a recent study by Orimisan et al. (2024) investigation of precisely five heavy metals (copper, lead, and nickel iron, cadmium,) were scrutinized in two vegetables ( Talinum triangulare and Chromolaena odorata) at two dumpsites in Ondo town, Nigeria. A dumpsite located between Ondo Town and Okeigbo was represented as site A and another dumpsite located at Okelaje-Ondo road was represented as Site B. Surprisingly the heavy metal levels identified in and vegetables were below WHO threshold limit with the exception of Cadmium in the control site except for cadmium in site A which was slightly higher. The heavy metals concentration examined in this investigation followed the sequence Fe > Cu > Cd > Ni > Pb for soil from locations A, and Fe > Pb > Cu > Ni > Cd for soil from sites B The dumpsites and the tested two vegetables revealed elevated levels of the heavy metals in comparison to the control area, suggesting a gradual accumulation of these metals in these vegetables. Although the concentration of heavy metals detected in the vegetables in these areas in Ondo town had minimal levels of the selected heavy metals tested, but the fact that they were present in the vegetables is a huge problem, hence may bio accumulate gradually, integrate into the food chain causing chronic debilitating health hazards.

A study by Suleiman et al. (2021) revealed heavy metal contamination in drinking water at six wards in Bade local government area, Yobe, Nigeria, which was as a turnout of pollution in the environment, ultimately affecting the drinking water in Gahua town Gombe negatively. The level of concentration of the following heavy metals; Iron, Manganese, Cadmium, Cobalt, Copper, Mercury and Nickel in boreholes across six wards the Gashua metropolis were assayed. The wards are as follows; Lawan Musa, Sabon Gari, Sarkin Hausawa Katuzu, Lawan Fannami, and Zango Wards. Water samples collected from eighteen sampling point across six urban wards showed no significant difference in terms of heavy metal contamination. Albeit, Suleiman et al. (2021) suggested that water from some ward were not suitable for drinking because of the huge build up some of the heavy metals that may cause kidney stones or renal failure.

The mean concentration from the study by Suleiman et al. (2021) for Cadmium showed higher levels in Lawan Fannami, Zango and Lawan Musa wards. Sabon Gari and Lawan Musa revealed higher values of Copper (Cu). Katuzu and Lawan Fannami have higher value of iron concentration that is higher than the acceptable standard, suggesting if precautionary measures are not taken it may lead to hideous diseases which can lead death. Alarmingly, all the six wards from this study have higher value of Lead (Pb) that is higher than the accepted standard using USEPA standard of 0.015 mg/kg. The continuous accumulation of this element may lead to serious health problem such as renal failure and kidney stones. Katuzu ward revealed higher concentration of Manganese (Mn) of 0.27, which is higher than the accepted standard. Zango, Sarkin Hausawa. The mean concentration for Mercury (Hg) shows that they are within acceptable value with no trace in Sabon Gari ward while a higher value in Lawan Fannami ward.

Taken together, this case study suggests a heavy metal contamination is of great concern in Nigeria owing to the fact that there is the presence of very much common heavy metals that may be injurious to the health and can cause serious havoc to the body of human and may even results into death.

A recent study by Nneoyi-Egbe (2024) on heavy metal contamination on shrimps and water at the great Kwa river, Calabar Cross River, Nigeria revealed pollution of both the shrimps and water from the Great Kwa River by a plethora of heavy metals, which in turn poses a health risk to aquatic ecosystem and humans. Amongst the heavy metals studied in this research in Calabar, Copper had the highest concentrations in shrimps (33.17 ± 0.79 ppm) and chromium water (27.68 ± 0.34ppm). The heavy metals were found in higher concentrations in the shrimp than in water, except for manganese which had a significantly (p<0.05) higher concentration in water (15.05 ± 0.67ppm) as against 14.02 ± 0.93ppm in shrimp).

The results of the research indicate significant Lead, Cadmium, Nickel, Chromium, Copper and Manganese content in shrimps and water from the Great Kwa River. It is a matter of great concern for both the environment and public health. Heavy metals are known to be toxic and can cause a range of health problems in humans, including neurological disorders, cancer, and kidney damage. Lead, Cadmium, Nickel and Chromium are particularly dangerous because they can accumulate in the body over time and cause chronic health effects. Moreover exposure to these heavy metals is associated with an increased risk of cardiovascular diseases, hypertension, and impaired cognitive function, neurological and behavioral changes, leading to decreased mobility, altered swimming behavior, and reduced foraging abilities. Moreover, lead can accumulate in the tissues of shrimps over time, leading to chronic exposure and bioaccumulation. This can result in bio magnification, a process where the concentration of lead increases as it moves up the food chain, ultimately affecting humans who consume contaminated seafood. Lead contamination in water can also have significant environmental and public health impacts. High levels of lead in water can cause a range of health problems in humans, including developmental delays in children, decreased intelligence quotient, and an increased risk of cardiovascular disease in adults. Taken together, for this case study, heavy metal concentration was present more in Fish than water at the great Kwa river, and this may cause deleterious effect to the humans consuming shrimps and periwinkle in that area.

Following a report on 6th November 2009, the Zamfara State Ministry of Health confirmed an unprecedented outbreak of child mortality in eight of the fourteen local government areas of the Shinkafi and Bakura communities in Zamfara State, Northern Nigeria. Affected communities were predominantly peasant farmers. ( Augusto et al., 2021). The mortality affected 34.6% of the population, with a case fatality rate of 30.5%. Over 52% of those who died were children less than five years old ( Augusto et al., 2021). It was further reported that the cause of the deaths was that the children had excessively high levels of lead in their blood. Four to five months later, two sister communities in the Gusau local government area of the state became afflicted as well. These two affected communities are situated away from the six contaminated villages in Bukuyyum and Anka local government areas of Zamfara State ( Abdullahi and Lasisi, 2024).

The Ogoni land is an oil-rich region located in the Niger Delta region of Nigeria. The land and its ethnic group, the Ogoni people, shot to worldwide attention in 1992 when the Nigerian military dictator suppressed a demonstration by the Ogoni people. The Ogoni land can best be described as the treasure or scrap of Nigeria ( Amosu and Adeosun, 2021). The authorities ordered the arrest and subsequently the trial and execution of nine of the movement’s leaders, including the most prominent and their offense was murder ( Okpebenyo et al., 2023). They had been convicted on what are generally considered to be false testimony and mishandled evidence. The movement fought against the disregard of environmental best practices by oil prospecting companies that held sway in the Ogoni land ( Okpebenyo et al., 2023). Companies developing the area were particularly criticized. Areas were inadequately treated after drilling had been completed, and the local people received little or no benefits from oil prospecting ( Sam et al., 2022).

Many lives have been lost indirectly and directly from the activities of the oil and gas explorers in Ogoni land and other inhabitants near these wells and rigs ( Nwoma and Anyika, 2024). The entire ecological system of Ogoni land is severely compromised, and the future of the people of Ogoni is shaky. Cases of massive standing surface oil pollution are very visible in numerous places in the area. Ogoni oil has gained a bad reputation among heavy metal users. In some cases, just the mention of the origin of the crude oil is enough to lose a sale or a customer ( Ben, 2022). Any breakdown of the process control in the industry processing Ogoni crude oil must result in a heavy metal disaster of of world proportions. The Ogoni land can best be described as the treasure or scrap of Nigeria ( Idialu, 2021).

Three major goldmines attributed to two distinct lead poisoning epidemics of extraordinary scale and remarkable geological background were recorded in Nigeria in recent history. The first, recorded in Bagega, was in 2010 ( Jamilu, 2023). In the aftermath of an episode of acute fatal childhood lead poisoning, with more than 400 elevated blood lead levels. What can be described as the second major goldmine activity occurred in Anka Local Government of Zamfara in 2020, with a similarity to the Bagega contamination ( Abu Khatita, 2024). Recorded cases of children with elevated blood lead levels have ranged from 24.3% to 60%; over 350 children were reported to have died, and in both of these cases, ( Akinwumi et al., 2023; Ezechukwu, 2023; Wilde et al., 2024) the mining involved grinding and milling of lead-rich ore, exposures from dust inhalation, and other pathways of the soil and water compartments ( Mahdi et al., 2023). Yet a third contamination with no epidemic status and of considerably fewer numbers was recorded in the Tsafe area in 2020, and the 2020 official status alone still pins both it and the 2020 exceedance incidences as being among the largest recorded in research that examined this throughout the world ( Kasongo et al., 2024). A characteristic that has generally defined gold mining in Nigeria is that the mining and grinding of ore releases airborne dust that contains lead, cadmium, mercury, cyanide, and/or other substances used in the process ( Escobedo-Monge et al., 2024).

Another incident of heavy metal contamination with conditions similar to the case described above occurred at the Itakpe iron ore mine in Nigeria in 1985 ( Akande et al., 2020). Geologically, there are suspicions that manganese was present in heavy metal concentrations, both as an oxide and as a carbonate ( Barde et al., 2024). The incident affected over 10 km of creeks lying near the exploration mine. The river contained high concentrations of iron and manganese deriving from the presence of iron ore on the plateau ( Isinkaye et al., 2023).

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