Bisphenol-A in Wistar Rats: Toxicological Study as Mitochondrial Disrupting Agent

  • Ahmad Zahak School of Pharmacy, OPJS University, Churu, Rajasthan (India)
  • Rohit Saraswat School of Pharmacy, OPJS University, Churu, Rajasthan (India)

Abstract

BPA is an EDC which is continuously released into the environment because of its extensive usage as plasticizer and other industrial applications. The present study establishes BPA induced alterations in mitochondrial marker enzymes and hence cause mitochondrial dysfunction. Studies were performed to evaluate the histopathological changes in tissue on exposure to different doses of BPA for different time periods.  Light microscopic examination of samples was done to evaluate the possible changes caused by treatment of different doses of BPA. After getting the results in light microscopy the changes and damage caused by BPA ultra-structurally were observed.  Light microscopic study showed that BPA exposure for short duration of 7 days did not resulted in significant change in histology of Rat of treated animals. Light microscopic observations showed that low doses of BPA (5 and 10 mg/kg body weight) exposure for 14 days caused reduction in the number of cells in the layers of seminiferous tubules. Highest dose of BPA treatment for 14 days caused much damage to the seminiferous tubules. There were many ultra-structural changes found in the treated groups as compared to the control group. Hence it can be stated that due to the toxic effect of BPA the mitochondrial marker enzymes have shown marked reduction in their activities.


Keywords: BPA, EDCs, Light microscopic, Mitochondria and Toxicity.

Downloads

Download data is not yet available.

References

1. Sajiki J, Yonekubo J. 2004. Leaching of Bisphenol A (BPA) from Polycarbonate Plastic to WaterContaining Amino Acids and Its Degradation by Radical Oxygen Species. Chemosphere 55: 861-867.
2. Miao S, Kou Z, Gao Z. 2009. Effect of bisphenol A on the structure of organs and the expression of some cytokines in rats. Journal of hygeine research. 38:11-4.
3. Dobrzynska MM, Radzikowska J. 2010. Frequency of micronuclei in reticulocytes of male mice exposed to bisphenol A and to a combination of x-rays and bisphenol A. Rocz. Panstw. Zakl. Hig. 61:129-133.
4. Schecter A, Malik N, Haffner D, Smith S, Harris TR, Paepke O, Birnbaum L. 2010. Bisphenol A (BPA) in U.S. Food. Environ. Sci. Technol. 44:9425–9430.
5. Liao C, Kannan K. 2011. Occurrence of Bisphenol A in Paper and Paper Products: Implications for Human Exposure. Environ. Sci. Technol. 45: 9372-9379.
6. Morrissey RE, George JD, Price CJ, Tyl RW, Marr MC, Kimmel CA. 1987. The developmental toxicity of Bisphenol A in rats and mice. Fundam. Appl. Toxicol. 8:571-582.
7. Krishnan AV, Stathis P, Permuth SF, Tokes L, Feldman D. 1993. Bisphenol-A: an estrogenic substance is released from polycarbonate flasks during autoclaving. Endocrinology 132:2279-2286.
8. Chun TY, Gorski J. 2000. High concentrations of bisphenol A induce cell growth and prolactin secretion in an estrogen-responsive pituitary tumor cell line. Toxicol. Appl. Pharmacol. 162: 161-165.
9. Brotons JA, Olea-Serrano MF, Villalobos M, Pedraza V, Olea N. 1995. Xenoestrogens released from lacquer coatings in food cans. Environ. Health Perspect. 103:753-758.
10. Yoo SD, Shin BS, Kwack SJ, Lee BM 2000: Pharmacocinetic disposition and tissue distribution of bisphenol A in rats after intravenous administration. J Toxicol. Environ. Health A 61:131-139.
11. Wetherill Y B, Akingbemi B, Kanno J, McLachlan J A, Nadal A, Sonnenschein C, Watson J A,
12. Nakagawa Y, Tayama S. 2000. Metabolism and cytotoxicity of bisphenol A and other bisphenols in isolated rat hepatocytes. Arch. Toxicol. 74:99–105.
13. Monroe RK, Halvorsen SW. 2009. Environmental toxicants inhibit neuronal Jak tyrosine kinase by mitochondrial disruption. Neurotoxicology 30:589–598.
14. IPCS. 2002. Global assessment of the state-of-the-science of endocrine disruptors. In: Damstra T, Barlow S, Bergman A, Kavlock R, Kraak Van der. (eds.), International Programme on Chemical Safety: World Health Organisation.
15. Belluzzi E, Bisaglia M, Lazzarini E, Tabares LC, Beltramini M, Bubacco L. 2012. Human SOD2 modification by dopamine quinones affects enzymatic activity by promoting its aggregation: possible implications for Parkinson's disease. PLoS One 7:e38026.
16. Kwak HI, Bae MO, Lee MH, Lee YS, Lee BJ, Kang KS, Chae CH, Sung HJ, Shin JS, Kim JH, Mar WC, Sheen YY, Cho MH. 2001. Effects of nonylphenol, bisphenol A, and their mixture on the viviparous swordtail fish (Xiphophorus helleri). Environ. Toxicol. Chem. 20:787-95.
17. Sayeed I, Parvez S, Winkler-Stuck K, Seitz G, Trieu I, Wallesch CW, Schonfeld P, Siemen D. 2006. Patch clamp reveals powerful blockade of the mitochondrial permeability transition pore by the D2-receptor agonist pramipexole. FASEB J 20:556–558.
18. Howdeshell KL, Hotchkiss AK, Thayer KA, Vandenbergh JG, Vom Saal. 1999. Environmental Toxins: Exposure to Bisphenol A Advances Puberty. Nature 401:763- 764.
19. Ceccarelli I, Della Seta D, Fiorenzani P, Farabollini F, Aloisi AM. 2007. Estrogenic chemicals at puberty change ERalpha in the hypothalamus of male and female rats. Neurotoxicol. Teratol. 29:108-15.
20. Takayanagi S, Tokunaga T, Liu X, Okada H, Matsushima A, Shimohigashi Y. 2006. Endocrine disruptor bisphenol A strongly binds to human estrogen-related receptor gamma (ERRgamma) with high constitutive activity. Toxicol. Lett. 167:95-105.
21. Bartsch H, Nair J. 2000. Ultrasensitive and specific detection methods for exocyclic DNA adducts: markers for lipid peroxidation and oxidative stress. Toxicology 153:105-114.
22. Sun Y. 1990. Free radicals, antioxidant enzymes, and carcinogenesis. Free Radical Biol. Med. 8:583-599.
23. Kayanoki Y, Fuji J, Islam KN, Kawata S, Matsuzawa Y, Taniguchi N. 1996. The protective role of glutathione peroxidase in apoptosis induced by reactive oxygen species. J Biochem. 119:817-822.
24. Tachibana T, Wakimoto Y, Nakamuta N, Phichitraslip T, Wakitani S, Kusakabe K, Hondo E, Kiso Y. 2007. Effects of bisphenol A (BPA) on placentation and survival of the neonates in mice. J. Reprod. Dev. 53:509–514.
25. Maffini MV, Rubin BS, Sonnenschein C, Soto AM. 2006. Endocrine disruptors and reproductive health: The case of bisphenol-A. Mol. Cell. Endocrinol. 254-255:179–186.
26. Seshagiri PB. 2001. Molecular insights into the causes of male infertility. J. Biosci. 26:429-435.
27. Knez J. 2013. Endocrine-disrupting chemicals and male reproductive health. Reprod. Biomed. Online. doi:pii: S1472-6483(13)00069-2. 10.1016/j.rbmo.2013.02.005. [Epub ahead of print].
28. Fusani L, Della Seta D, Dessì-Fulgheri F, Farabollini F. 2007. Altered reproductive success in rat pairs after environmental-like exposure to xenoestrogen. Proc. Biol. Sci. 274:1631-6.
29. Aitken RJ, Koopman P, Lewis SE 2004. Seeds of concern. Nature 432:48–52.
30. Toyama Y, Yuasa S. 2004. Effects of neonatal administration of 17 β-estradiol, β-estradiol, 3-benzoate, or bisphenol A on mouse and rat spermatogenesis. Reprod. Toxicol. 19:181-188.
31. Dan Z, Popov Y, Patsenker E, Preimel D, Liu C, Wang XD, Seitz HK, Schuppan D, Stickel F. 2005. Hepatotoxicity of alcohol-induced polar retinol metabolites involves apoptosis via loss of mitochondrial membrane potential. FASEB J. 19:845-7.
32. Andriana BB, Tay TW, Hiramatsu R, Awal MA, Kanai Y, Kurohmaru M, Hayashi Y. 2004. Bisphenol A-induced morphological alterations in Sertoli and spermatogenic cells of immature Shiba goats in vitro: An ultrastructural study. Reproductive Medicine and Biology 3:205–210.
33. Kashiwagi A, Utsumi K, Kashiwagi K, Ohta S, Sugihara K, Hanada H, Kitamura S. 2008. Effects of endocrine disrupting chemicals on amphibian metamorphosis and mitochondrial membrane permeability transition. J. Health Sci. 54:273-280.
34. Nakagawa Y, Tayama S. 2000. Metabolism and cytotoxicity of bisphenol A and other bisphenols in isolated rat hepatocytes. Arch. Toxicol. 74:99–105.
35. Perkins GA, Scott R, Perez A, Ellisman MH, Johnson JE, Fox DA. 2012. Bcl-xL-mediated remodeling of rod and cone synaptic mitochondria after postnatal lead exposure: Electron microscopy, tomography and oxygen consumption. Molecular Vision. 18:3029-3048.
Statistics
3 Views | 2 Downloads
How to Cite
Zahak, A., & Saraswat, R. (2020). Bisphenol-A in Wistar Rats: Toxicological Study as Mitochondrial Disrupting Agent. Journal of Drug Delivery and Therapeutics, 10(1), 81-91. https://doi.org/10.22270/jddt.v10i1.3849