Systematic review: Effect of feeding rich in CYP2A6 and glutathione enzymes on decreasing nicotine levels in the body of smokers

1. Introduction

Smoking is one of the health problems because it can cause various diseases such as cancer, disability, and death. According to Riskesdas data in 2021, the percentage of smokers in Indonesia who are under the age of 18 with a male gender reaching 7.14% while a female gender reaches 0.09% (Badan Pusat Statistik, 2021). Cigarettes can be said to be addictive because they can cause addiction to their users. This is inseparable from the ingredients contained in cigarettes, one of which is nicotine (Hisamuddin et al., 2020). Nicotine has an addictive effect on its users because it can have a pleasant and calming effect.

Research conducted (Dwinta, 2020) related to nicotine dependence in smokers stated that more than 4% of respondents experienced high levels of nicotine dependence, and respondents with moderate dependence levels reached 21%. The high rate of nicotine dependence for smokers can have a negative impact on the body. According to research conducted by (Nufus et al., 2020), the nicotine content in cigarettes can increase MDA levels and reduce SOD levels. So cigarette addicts will experience oxidative stress as a result of increased MDA levels (Tualeka et al., 2019). Nicotine can produce cotinine which has an impact on a person’s psychology. This is in line with research conducted by Zainusshalihin et al. (2021), cotinine which is the result of nicotine metabolites can provide a stimulant effect so that smokers can experience symptoms of depression.

In addition to having a negative psychological impact, nicotine also has a physiological impact. According to previous research, nicotine can affect fracture healing. This depends on the level of nicotine in the patient’s body (Esau et al., 2020). However, the content contained in nicotine can cause an opiate effect so smokers will feel sick and uncomfortable or commonly called a withdrawal effect if cigarette consumption is stopped. Nicotine can enter body through the respiratory tract easily (Nirmawati et al., 2018).

Nicotine or C₁₀H₁₄N₂ compounds are classified as organic alkaloids. This compound consists of carbon, hydrogen, nitrogen, and oxygen. In 100 grams of tobacco, the concentration of nicotine can reach 5% which is about 8-20 mg of nicotine (Rachmah et al., 2022). Nicotine can be absorbed into the human body through the skin, lungs, and mucous membranes. Nicotine metabolism in the human body differs from one individual to another. This difference can be influenced by various factors such as the enzyme CYP2A6 and glutathione (Tualeka et al., 2018). The enzyme ZYP2A6 is an enzyme that is responsible for the metabolism of nicotine into cotinine in the range of 70-90% (Mayazi, 2014).

CYP2A6 enzymes can inhibit the effectiveness of the liver in digesting nicotine. Previous studies have shown that foods containing the CYP2A6 enzyme, which is a nicotine biotransformation enzyme, have been shown to reduce nicotine levels in smokers (Tualeka, 2020). Cigarette addicts who have abnormalities in the CYP2A6 enzyme will have a greater nicotine effect than other smokers (Tualeka et al., 2020). The presence of nicotine in the body will have an impact on health problems.

Meanwhile, glutathione is a tripeptide -L-glutamyl-L-cysteineyl- glycine, which is found in all mammalian tissues and is present in high concentrations, especially in the liver. Glutathione (GSH) with the enzyme glutathione peroxidase (GPx) can catalyze the reduction of fat hydroperoxides to alcohol and hydrogen peroxide to water (Sahri et al., 2019). During the catalysis process, the disulfide bonds of GSH will bind to form oxidized glutathione (GSSG), and the glutathione reductase enzyme can recycle GSSG into GSH again by oxidizing NADPH. When cells are exposed to oxidative stress, GSSG accumulation will occur and the GSH/GSSG ratio will decrease (Tualeka & Jalaludin, 2018). Based on the results of previous studies and studies, it is stated that the GCL gene polymorphism is a risk factor for oxidative stress susceptibility and the severity of pulmonary TB. If there is a GCL gene polymorphism, there will be a decrease in glutathione levels. If the level of glutathione is low, there will be an increase in oxidative stress (Yuniastuti, 2016).

From the description above, the authors are interested in studying the effect of giving doses of foods rich in CYP2A6 enzymes and glutathione to reduce nicotine levels in the body of smokers.

2. Methods

The research method used is the systematic literature review. The author uses data from various articles and references that can support the research. The article search was conducted in May 2022 via Google Scholar. The keywords used in the article search were foods rich in the CYP2A6 enzyme, glutathione in smokers, and nicotine levels. After the articles are collected, the next step is to do a screening using the PRISMA method. As a result, 4 articles of international repute were obtained (see Figure 1).

Figure 1. Diagram of the data search process.

The article was selected with several inclusion criteria including: the year of publication for the last 5 years from 2017-2022, using the experimental method, discussing the effect of food doses with CYP2A6 and glutathione enzymes on reducing nicotine levels, as well as full-text journals that can be accessed free of charge.

3. Results

From the search results through Google Scholar, we got 4 international standard journals that match the inclusion criteria. Of these 4 journals, there are 2 journals that discuss the effect of the CYP2A6 enzyme on reducing nicotine levels and 2 journals related to the effect of giving glutathione on nicotine levels. The following are the results of a literature review that match the inclusion criteria (see Table 1).

4. Discussion

From the 4 articles, it was found that all of them discussed the role of the CYP2A6 enzyme and glutathione in reducing nicotine levels and oxidative stress. All findings from literature sources use experimental research methods. In a study conducted by Tualeka and Nadhiroh (2019), it was stated that respondents who consumed foods rich in the CYP2A6 enzyme, namely beef liver, could increase the excretion of cotinine in the urine. In this study, 80% of respondents increased levels of cotinine excretion in the urine (Tualeka & Nadhiroh, 2019).

The decrease in nicotine levels when consuming foods rich in the CYP2A6 enzyme occurs because this process can convert nicotine into cotinine which is excreted in the urine. The released cotinine can reduce nicotine levels in the respondent’s body. Therefore, the consumption of foods with the CYP2A6 enzyme will have an impact on reducing the number of addictions to nicotine (Ayu et al., 2018). The decrease in nicotine levels in the body is not only influenced by the CYP2A6 enzyme. Characteristics of respondents include smoking habits, age, duration and number of cigarettes smoked can affect the concentration of nicotine in the smoker’s body (Tualeka & Nadhiroh, 2019).

In a study conducted by Lee (2018), it was stated that the administration of standard Chinese L, Smilax root extract (SSCR) containing chlorogenic acid on nicotine detoxification through upregulation of the CYP2A6 enzyme can detoxify nicotine by increasing the conversion of nicotine into cotinine. SSCR can induce the CYP2A6 enzyme transcriptionally and contribute to the activation of nicotine into cotinine in the liver and lungs (Bada et al., 2018). SSCR induced by the CYP2A6 enzyme can be used to prevent oxidative stress-related diseases caused by nicotine exposure.

Tobacco contains many carcinogenic substances that can be activated through xenobiotic enzymes. The CYP2A6 enzyme plays an important role in the metabolism of nicotine to cotinine (Soegianto et al., 2010). To increase the CYP2A6 enzyme in the body, it can be done by consuming foods such as broccoli. Previous studies have shown that the CYP2A6 enzyme can be increased by 1.4 to 5.5 times by consuming 500 g/day of broccoli (Chenoweth et al., 2013).

Besides the role of the CYP2A6 enzyme which can transcribe nicotine into nicotine, there is also the role of glutathione which can reduce nicotine levels in the body exposed to cigarette smoke. A study conducted by Zaki et al. (2018) stated that onion extract and Nigella Sativa (NS) were proven to be able to attenuate nicotine levels through antioxidants and peroxidative anti-lipids. Nicotine exposure can lower antioxidant levels. Experimental animals exposed to nicotine showed a significant reduction in SOD and CAT levels by 58% and 26%, respectively.

The administration of onion extract and NS is known to increase the levels of SOD and CAT by 122% and 29.4%, respectively. Between the administration of onion extract and NS, a more prominent increase was found in the administration of NS. The administration of nicotine in experimental animals showed lower levels of pulmonary GSH and ELF GSH by 53% and 44%. The use of onion extract and NS can increase the levels of GSH and ELF GSH by 37% and 69%, respectively. A study conducted by Zahran and Emam (2018) stated that the administration of Spirulina (SP) supplementation induced with nicotine was proven to increase antioxidants. Spirulina administration has an impact on reducing oxidative damage due to nicotine exposure. In experimental animals, it was found that MDA levels were recorded as high. MDA is one of the signs of cellular defects caused by free radicals (Zahran & Emam, 2018). High levels of MDA can be suppressed by giving Spirulina (SP).

Meanwhile, the activity of GST and GSH in the kidney decreased significantly. The decrease was found in the NIC group. While the administration of SP with NIC can significantly increase GST activity and GSH (glutathione) levels. So it can be concluded that the administration of Glutathione can inhibit free radicals caused by nicotine. Glutathione can be increased by giving Spirulina.

5. Conclusions

Based on the results of a literature review, it was found that there was a relationship between the administration of CYP2A6 enzymes and glutathione to reduce nicotine levels and oxidative stress in the body of smokers. CYP2A6 enzymes and glutathione can be increased by consuming beef, onion extract, spirulina (SP), standard Chinese L. Smilax root extract (SSCR) containing chlorogenic acid, broccoli, and Nigella Sativa (NS). On the other hand, the results literature review has limitations. There is a need for additional factors, namely inhibitors of reducing nicotine levels to determine the effectiveness of the treatment. This study can be used as a reference to reduce nicotine levels and oxidative stress in smokers.

Ethics and consent

Ethical approval and consent statement were not required.