Prevention Of The Toxicity Of Nicotine By Supplementation Of Green Tea
Toxic influences of nicotine can be seen in the structural appearance changes and upregulated the antioxidant and tumorigenic related genes expression in liver, lung, and kidney tissues of treated animals. In this investigation, we study the toxicity of nicotine along with the possible protective effect of green tea at the tested dose level by daily interaperitoneal injection on some organs of BALB/c mice. All these pathophysiological and molecular alterations were significantly improved when the nicotine treated groups were given green tea. Our results propose different effects of nicotine on different organs which could be due to the differential load of oxidative stress generated by nicotine in these organs. The toxicity of nicotine in different organs like liver, lung, and kidney is due to the formation of the free radical species.
Nicotine increases free radicals formation in cultured rat hepatocytes and kidney cells and that it induces lipoperoxidation and oxidative stress in microsomal preparations from humans, which might clarify the upregulated antioxidant and mutagenic related genes expression after the long-term administration of nicotine in the present study.
Our study on liver, lung, and kidney tissues revealed that nicotine can modify the expression of a number of antioxidant and mutagenic related genes whose products are implicated in the pathogenesis and carcinogenesis in these tissues. As nicotine is one of the main constituents of cigarette smoke, these data will have importance in the understanding of pathological effects of cigarette smoking.
Nicotine decreases the content of protein sulfhydryl groups and lead to protein thiol oxidation in rat liver cells, possibly caused by the nicotine-induced GSH depletion. A same mechanism is suggested for the inhibition detected in other enzymes. Nicotine might also decrease the protein levels of antioxidant enzymes, because a clear inhibitory effect of the drug on the synthesis of protein in the rat liver cells has been revealed). The free radicals formation was associated by decreased protein levels of CAT and SOD. Importantly, the nicotine induction reduces the enzymatic and nonenzymatic antioxidant protection systems in rats, making them more vulnerable to oxidative injury and compromising the antioxidant ability of the liver to effectively scavenge the ROS created during nicotine treatment.
Several natural dietary products act as inhibitors of carcinogenesis. The study by Cheng et al. has also revealed that garlic squeeze, one of these dietary constituents, are beneficial to stop the harmful adduct formation, and thus to block the potential carcinogenesis made by nicotine. In addition, nicotine play important role in invasion and metastasis of different cancer types through the activation of COX-1 and COX-2 gene expression. Therefore, COX-1 and COX-2 are an important oncogenes in the pathogenesis of cancer, in our study, upregulation COX-1 and COX-2 expression by nicotine treatment was prevented by supplementation of green teaIn this study, the histological examinations of lung tissue of mice treated with nicotine showed variable degrees of alterations. This was demonstrated by the thickening of interalveolar septa, wide damage of wall of the alveoli and irregular air space. After four weeks of nicotine injection, the lung is highly susceptible to free radical generation. Nicotine is quickly absorbed into the circulatory system and processed in the liver by cytochrome P450, liver cell damage, inflammation and triggering of Kuppfer cells may be attributed to pro-inflamatory cytokines. The histological damage initiated by nicotine in this study by nicotine treatment may be attributed to decreases in glutathione peroxidase activity.
The progress of nicotine-induced hepatic injury changed the redox state with a diminished hepatic glutathione and increased the creation of lipid peroxidation products, which were prevented by treatment with green tea. Administration of green tea partly normalized the activity of antioxidants enzymes. It was revealed that the long-term administration of tobacco smoking can reduce the enzymatic antioxidant defense system of the rat kidneys. These changes may be one of the responsible reasons for smoking-induced inflammation in these organs.
In the present study, nicotine administration significantly decreases antioxidant enzymes gene expression in tissues, indicating that antioxidant enzymes were used as an antioxidant for the detoxification of toxic oxygen metabolites, enhancing the exposure of the tissues to oxidative injury. In contrast, green tea treatment, due to its high antioxidant activity, reduced the nicotine-induced oxidative damage and restored the antioxidant enzymes gene expression significantly. These data together support the assumption that cellular oxidative stress is a critical in nicotine-mediated tissue damage, and propose that antioxidant plans intended either to scavenge free radicals or to inhibit free radical creation to protect tissues against nicotine toxicity.
The defensive role of green tea against nicotine induced oxidative stress may be clarified by the large amounts of catechins, including epigallocatechin gallate that accounts for more than 80% of all active constituents in green tea and has been revealed to have the highest antioxidant activity among numerous compounds. The content of epigallocatechin gallate in green tea is tenfold greater than that in black tea. Unlike black tea, green tea also has ascorbic acid. These results propose that green tea may act as an effective antioxidant. So, the results obtained with BALB/c mice in our present study would imply that regular intake of green tea may protect against the risk of developing cancer and tissues damage.
Conclusion
Exposure of BALB/c mice model to nicotine caused oxidative stress, altered the cellular antioxidant and mutagenic related gene expression, inflammation and tissues damage, which could be prevented by supplementation of green tea.
