Evaluation of Smokeless Tobaccos-induced Hepatotoxicity and Nephrotoxicity in Swiss Albino Mice
Keywords:Glutathione, Hepatotoxicity, Nephrotoxicity, Smokeless Tobacco
AbstractThe massive global increase in tobacco use has become a public health problem worldwide. Gutka or gutkha and zarda are some of the widespread smokeless tobacco products commonly consumed in India. The present study aims at analyzing the histopathology and biochemical changes in the liver and kidney of Swiss albino mice following the treatment with some smokeless tobaccos. The animals in different groups were administered with low and high doses of aqueous solutions/ filtrates of a gutkha and a blend of combined pan masala and S-FOUR zarda daily by oral gavage for a month. After treatment, the liver and kidneys were collected for histopathological examination through light and transmission electron microscopy and reduced glutathione determination. At the same time, blood samples were collected for measuring the serum marker enzymes/biochemicals for liver and kidney functions. Histological and ultrastructural observations of the liver and kidney showed marked deleterious alterations in the structural architecture, suggesting the development of cytopathological tendency of the tissues after treatment with smokeless tobaccos. Serum biomarker enzymes for liver and kidney functions showed a considerable increase in all the parameters, thus, indicating adverse effects on their functional capabilities which substantiate the structural variations and development of hepatotoxicity and nephrotoxicity after treatment. The treated animals showed a significant decrease in GSH levels in these tissues which may cause decreased antioxidant and protective ability and may aid in developing the toxicity in the hosts. These toxicities could be attributable to various chemical constituents present which are needed to be analyzed and made known on the commercially available smokeless tobacco products/packets. It is suggested that addictive use of smokeless tobaccos could be a risk factor for many diseases and in developing countries like India, recognition of harmful consequences of their recurrent usage should be widely known to the public.
How to Cite
Tobacco. 2019. https://en.wikipedia.org/wiki/Tobacco.
WHO Report on the global tobacco epidemic. The MPOWER package. Geneva, Switzerland, 2008. p. 1–342.https://www.who.int/tobacco/mpower/mpower_report_ full_2008.pdf.
Smokeless Tobacco and Public Health: A Global Perspective Chapter 3. A Global view of Smokeless Tobacco products.2014. p. 75–114; Chapter 4. Health consequences of Smokeless Tobacco use. p. 115–42. National Cancer Institute and Centers for Disease Control and Prevention. Bethesda, MD: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention and National Institutes of Health, National Cancer Institute. NIH Publication No. 14-7983. 2014. https:// cancercontrol.cancer.gov/brp/tcrb/global-perspective/ SmokelessTobaccoAndPublicHealth.pdf.
WHO Report on the global tobacco epidemic. World Health Organization: Monitoring tobacco use and prevention policies.2017. p. 1–135. https://apps.who.int/iris/bitstream/han dle/10665/255874/9789241512824-eng.pdf?sequence=1.
WHO. Tobacco-free initiative. Tobacco: Deadly in any form or disguise. World Health Organisation: Geneva, Switzerland. 2006. https://www.who.int/tobacco/ wntd/2006/materials/wntd_2006_report.pdf.
Dobe M, Sinha DN, Rahman K. Smokeless Tobacco use and its implications in WHO. Southeast Asia Region. Indian J Public Health. 2006; 50:70–5.
Chadda RK, Sengupta SN. Tobacco use by Indian adolescents.Tobacco Induced Diseases. 2002; 1(2):111–9.PMid: 19570251 PMCid: PMC2671647. https://doi.org/10.1186/1617-9625-1-2-111.
Appendix B - Global Smokeless Tobacco product fact sheets: Smokeless Tobacco and public health: Global perspective.2019. P. B-1–64. https://cancercontrol.cancer.gov/brp/tcrb/global-perspective/Appendix_B_Smokeless Tobacco And PublicHealth.pdf '.
Sedlak J, Lindsay RH. Estimation of total protein, proteinbound and non-protein sulfhydryl groups in tissue with Ellman's reagent. Anal Biochem. 1968; 25:192–205. https:// doi.org/10.1016/0003-2697(68)90092-4.
Brzoska MM, Jakoniuk MM, Marcinkiewicz BP, Sawicki B. Liver and kidney function and histology in rats exposed to cadmium and ethanol. Alcohol and Alcoholism. 2003; 38(1):2–10. PMid: 12554600. https://doi.org/10.1093/ alcalc/agg006.
Travlos GS, Morris RW, Elwell MR, Duke A, Rosenblum S, Thompson MB. Frequency and relationship of clinical chemistry and liver and kidney histopathology findings in 13-week toxicity studies in rats. Toxicology. 1996; 107:17– 29. https://doi.org/10.1016/0300-483X(95)03197-N.
Crissman JW, Goodman DG, Hildebrandt PK, Maronpot RR, Prater DA, Riley JH, Seaman WJ, Thake DC. Best practice guideline: Toxicologic histopathology. Toxicol Pathol. 2004; 32:126–31. PMid: 14713558. https://doi.org/10.1080/01926230490268756.
Kim TW, Lim JH, Song IB, Park SJ, Yang JW, Shin JC, Suh JW, Son HY, Cho ES, Kim MS, Lee SW, Kim JW, Yun HI.Hepatoprotective and anti-hepatitis C viral activity of Platycodon grandiflorum extract on carbon tetrachlorideinduced hepatic injury in mice. J Nutr Sci Vitaminol (Tokyo). 2012; 58(3):187–94. PMid: 22878389. https://doi.org/10.3177/jnsv.58.187.
OECD. OECD guidelines for the testing of chemicals: Acute oral toxicity-up-and-down-procedure (UDP). Paris, France: Organization for Economic Co-operation and Development (OECD); Oct 2008. p. 1–27.
Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG. Selenium: Biochemical role as a component of glutathione peroxidase. Science. 1973; 179:588–90. PMid: 4686466. https://doi.org/10.1126/science.179.4073.588.
Snehu S, Yabagi MY. Investigation of acute and subchronic toxicity of aqueous extract of Nigerian nasal snuff in Wistar albino rats. AJAS. 2019; 12(1):37–44. https://doi.org/10.3923/ajaps.2019.37.44.
Chenlin Y, Zhang Z, Yangang L, Yong Y, Chen Y, Du X, Chen J, Feng S, Hu J, Cui S, Lu G. Toxicity of Smokeless Tobacco Extract after 184-day repeated oral administration in rats.Int J Environ Res Public Health. 2016; 13(3):1–16. PMid: 26959038 PMCid: PMC4808944. https://doi.org/10.3390/ ijerph13030281.
Mukhaini NA, Omar TB, Eltayeb E, Shihi AA, Riyami NA, Belushi JA, Adawi KA. Liver and kidney toxicity induced by Afzal Smokeless Tobacco product in Oman. Tissue and Cell. 2017; 49(2):307–14. PMid: 28238347. https://doi.org/10.1016/j.tice.2017.01.008.
Lowe JS, Anderson PG. Stevens and Lowe's Human Histology, 4th Ed. Imprint: Mosby Ltd; 2014. p. 1–448.
Alarami AMJ. Histopathological changes in the liver and kidney of albino mice on exposure of insecticide, dimethoate.Int J Curr Microbiol App Sci. 2015; 4(7):287–300.
Yu C, Zhang Z, Liu Y, Zong Y, Chen Y, Du X, Chen J, Feng S, Hu J, Cui S, Lu G. Toxicity of Smokeless Tobacco Extract after 184-day repeated oral administration in rats. Int J Environ Res Public Health. 2016; 13:281–96. https://doi. org/10.1111/iwj.12581.
Treasure J. Urtica semen reduces serum creatinine levels. J Am Herbal Guild. 2003; 4:22–5.
Dollah MA, Parzhikar S, Izwan M. Effect of Nigella sativa on the kidney function in rats. Avicenna J Phytomed. 2013; 3(2):152–8.
Gowda S, Desai PB, Kulkarni SS, Hull VV, Math AK, Vernekar SN. Markers of renal function tests. N Am J Med Sci. 2010; 2(4):170–3.
Mitchell HR, Kline W. Core curriculum in nephrology, renal function testing. Am J Kidney Dis. 2006; 47:174–83. PMid: 16377400. https://doi.org/10.1053/j.ajkd.2005.08.038.
Tucker LA. Use of Smokeless Tobacco, cigarette smoking and hypercholesterolemia. Am J Public Health. 1989; 79(8):1048–50. PMid: 2751026 PMCid: PMC1349909.https://doi.org/10.2105/AJPH.79.8.1048.
Sajid F, Bano S. Effects of smokeless dipping tobacco (Naswar) consumption on antioxidant enzymes and lipid profile in its users. Pak J Pharm Sci. 2015; 28(5):1829–33.
Siegel D, Benowitz N, Ernster VL, Grady DG, Hauck WC.Smokeless Tobacco, cardiovascular risk factors and nicotine and cotinine levels in professional baseball players. Am J Public Health. 1992; 82(3):417–21. PMid: 1536359 PMCid: PMC1694380. https://doi.org/10.2105/AJPH.82.3.417.
Wallenfeldt K, Hulthe J, Bokemark L, Wikstrand J, Fagerberg B. Carotid and femoral atherosclerosis, cardiovascular risk factors and C-reactive protein in relation to Smokeless Tobacco use or smoking in 58-year-old men.J Intern Med. 2001; 250(6):492–501. PMid: 11902817.https://doi.org/10.1046/j.1365-2796.2001.00917.x.
Willis DN, Popovech MA, Gany F, Hoffman C, Blum JL, Zelikoff JT. Toxicity of gutkha, a Smokeless Tobacco product gone global: Is there more to the toxicity tan nicotine?Int H Environ Res Public Health. 2014; 11:919–33.
Meister A, Anderson ME. Glutathione. Ann Rev Biochem.1983; 52:711–60. PMid: 6137189. https://doi.org/10.1146/ annurev.bi.52.070183.003431.
Bharavi K, Gopala Reddy A, Rao GS, Rajasekhara Reddy A, Rama Rao SV. Reversal of cadmium-induced oxidative stress in chicken by herbal adaptogens. Withania somnifera and Ocimum sanctum. Toxicology Internat. 2010; 17(2):59–63. PMid: 21170246 PMCid: PMC2997456.https://doi.org/10.4103/0971-6580.72671.
Avti PK, Kumar S, Pathak CM, Vaiphei Kim, Khanduja KL.Smokeless Tobacco impairs the antioxidant defense in liver, lung and kidney of rats. Toxicol Sci. 2006; 89(2):547–53.PMid: 16280382. https://doi.org/10.1093/toxsci/kfj041.
Yildiz D, Liu YS, Ercal N, Armstrong DW. Comparison of pure nicotine- and Smokeless Tobacco Extract-induced toxicities and oxidative stress. Arch Environ Contam Toxicol. 1999; 37(4):434–9. PMid: 10508890. https://doi.org/10.1007/s002449900537.