N-Acetylcysteine Improves Acrylamide-Induced Changes in Ovarian Tissue and Serum Levels of Pituitary-Ovarian Axis Hormones in Adult Rats

Year 2019, Volume: 78 Issue: 2, 75 - 81, 06.12.2019

Marziyeh Naimi Mehrdad Shariati , Syrus Naimi Mohammad Amin Edalatmanesh

Abstract

Objective: The purpose of this study was to evaluate the protective effect of N-acetylcystein (NAC) on ovarian tissue and serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and progesterone in Acrylamide (AA)treated adult rats. Materials and Methods: Forty-two adult female Wistar rats were randomly assigned into 7 groups of 6 including: a control group without treatment, a placebo group received distilled water intraperitoneally, an AA group received 50 mg/kg by oral gavage, a NAC group received 40 mg/kg intraperitoneally, an AA+NAC10, AA+NAC20 and an AA+NAC40 groups received 10, 20 and 40 mg/kg of NAC intraperitoneally, respectively and then also received 50 mg/kg AA by oral gavage for 28 days. Serum levels of FSH, LH, estradiol and progesterone were measured by radioimmunoassay method and ovarian tissue was evaluated histopathologically. Results: Administrating AA alone decreased the number of ovarian follicles, corpus luteum and the levels of FSH, estradiol and progesterone, while increased the number of atretic follicles and LH level compared to the control, placebo and NAC groups (p<0.05). The administration of NAC alone had no effect on the number of ovarian follicles, corpus luteum and the level of hormones compared to the control and placebo groups (p>0.05). Following AA+NAC20 and AA+NAC40 administration and not AA+NAC10, the number of ovarian follicles, corpus luteum and also the levels of FSH, estradiol and progesterone increased, while the number of atretic follicles and LH level decreased (p<0.05), which was in a dose-dependent manner compared to the AA group. Conclusion: NAC could recover the AA female rat reproductive toxicity in a dose-dependent manner, and improved folliculogenesis. 

Keywords

Acrylamide, n-acetylcystein, ovary, estradiol, rat

Supporting Institution

This study was supported by the Research Fund of the Islamic Azad University of Shiraz.

Project Number

IR.Shiraziau 1633052565

Thanks

This study is the result of a Ph.D. thesis in developmental biology. The authors would like to thank the Islamic Azad University of Kazerun and the Islamic Azad University of Shiraz for their cooperation during this study.

References

• 1. Rahangadale S, Jangir BL, Patil M, Verma T, Bhandarkar A, Sonkusale P, et al. Evaluation of protective effect of vitamin E on acrylamide induced testicular toxicity in wister rats. Toxicol Int 2012; 19(2): 158-61.
• 2. Olesen PT, Olsen A, Frandsen H, Frederiksen K, Overvad K, Tjønneland A. Acrylamide exposure and incidence of breast cancer among postmenopausal women in the Danish Diet, Cancer and Health Study. Int J Cancer 2008; 122(9): 2094-100.
• 3. Yener Y and Kalipci E. The carcinogenic effects of acrylamide formed during cooking of some foods. Academic J Cancer Res 2009; 2(1): 25-32.
• 4. Lingnert H, Grivas S, Jagerstad M, Skog K, Tornqvist M, Aman P, et al. Acrylamide in food: mechanisms of formation and in influencing factors during heating of foods. Scand J Nutr 2002; 46(4): 159-72.
• 5. Klaunig JE. Acrylamide carcinogenicity. J Agric Food Chem 2008; 56(15): 5984-8.
• 6. Barber DS, Hunt JR, Ehrich MF, Lehning EJ, Lopachin RM. Metabolism, toxicokinetics and hemoglobin adduct formation in rats following subacute and subchronic acrylamide dosing. Neurotoxicology 2001; 22(3): 341-53.
• 7. Tyl RW and Friedman MA. Effects of acrylamide on rodent reproductive performance. Reprod Toxicol 2003; 17(1): 1-13.
• 8. Collí-Dulá RC, Friedman MA, Hansen B, Denslow ND. Transcriptomics analysis and hormonal changes of male and female neonatal rats treated chronically with a low dose of acrylamide in their drinking water. Toxicol Rep 2016; 19(3): 414-26.
• 9. Zarei M and Shivanandappa T. Amelioration of cyclophosphamide-induced hepatotoxicity by the root extract of Decalepis hamiltonii in mice. Food Chem Toxicol 2013; 57: 179-84.
• 10. Wei Q, Li J, Li X, Zhang L, Shi F. Reproductive toxicity in acrylamide-treated female mice. Reprod Toxicol 2014; 46: 121-8.
• 11. ALKarim S, ElAssouli1 S, Ali S, Ayuob N, ElAssouli Z. Effects of low dose acrylamide on the rat reproductive organs structure, fertility and gene integrity. Asian Pac J Reprod 2015; 4(3): 179–87.
• 12. DuanX, Qiao- Wang C, Chen KL, Zhu CC, Liu J, Suna SC. Acrylamide toxic effects on mouse oocyte quality and fertility in vivo. Sci Rep 2015; 5: 11562.
• 13. Kunle-Alabi OT, Akindele OO, Odoh MI, Oghenetega BO, Raji Y. Comparative effects of coconut water and N-Acetyl cysteine on the hypothalamo-pituitary-gonadal axis of male rats. Songklanakarin J Sci Technol 2017; 39(6): 759-64.
• 14. Ercal N, Treeratphan P, Lutz P, Hammond TC, Matthews RH. N-acetylcysteine protects chinese hamster ovary (CHO) cells from lead-induced oxidative stress. Toxicology 1996; 108(1-2): 57- 64.
• 15. Xue C, Liu W, Wu J, Yang X, Xu H. Chemoprotective effect of N-acetylcysteine (NAC) on cellular oxidative damages and apoptosis induced by nano titanium dioxide under UVA irradiation. Toxicol in Vitro 2011(1); 25: 110-6.
• 16. Demedts M, Behr J, Buhl R, Costabel U, Dekhuijzen R, Jansen HM, et al. High-dose acetylcysteine in idiopathic pulmonary fibrosis. N Engl J Med. 2005; 353(21): 2229-42.
• 17. Chiew AL, Isbister GK, Duffull SB, Buckley NA. Evidence for the changing regimens of acetylcysteine. Br J Clin Pharmacol 2016; 81(3): 471–81.
• 18. Marcondes FK, Bianchi FJ, Tanno AP. Determination of estrous cycle phases of rats: some helpful considerations. Braz J Biol 2002; 62(4A): 609-14.
• 19. Camacho L, Latendresse JR, Muskhelishvili L, Patton R, Bowyer JF, Thomas M, et al. Effects of acrylamide exposure on serum hormones,gene expression, cell proliferation, and histopathology in male reproductive tissues of Fischer 344 rats. Toxicol Lett 2012; 211(2): 135–43.
• 20. Pan X, Wu X, Yan D, Peng C, Rao C, Yan H. Acrylamide-induced oxidative stress and inflammatory response are alleviated by N-acetylcysteine in PC12 cells: Involvement of the crosstalk between Nrf2 and NF-κB pathways regulated by MAPKs. Toxicol Lett 2018; 288: 55-64.
• 21. Kojsová S, Jendeková L, Zicha J, Kunes J, Andriantsitohaina R, Pechánová O. The effect of different antioxidants on nitric oxide production in hypertensive rats. Physiol Res 2006; 55(Suppl): S316.
• 22. Galhardo MA, Júnior CQ, Riboli Navarro PG, Morello RJ, De Jesus Simões M, De Souza Montero EF. Liver and lung late alterations following hepatic reperfusion associated to ischemic preconditioning or N-acetylcysteine. Microsurgery 2007; 27(4): 295-9.
• 23. Usta U, Inan M, Erbas H, Aydogdu N, Puyan OF, Altaner S. Tissue damage in rat ovaries subjected to torsion and detorsion: effects of L-carnitine and N-acetyl cysteine. Pediatr Surg Int 2008; 24: 567-73.
• 24. Danilovic A, Lucon AM, Srougi M, Shimizu MHM, Lanhez LE, Nahas WC, et al. Protective effect of N-acetylcysteine on early outcomes of deceased renal transplantation. Transplant Proc 2011; 43: 14439.
• 25. Millea PJ. N-Acetylcysteine: Multiple clinical applications. Am Fam Physician 2009; 80: 265-9.
• 26. Mokhtari V, Afsharian P, Shahhoseini M, Kalantar SM, Moini A. A review on various uses of n-acetyl cysteine. Cell J 2017; 19(1): 11-17.
• 27. Altinoz E, Turkoz Y, Vardi N. The protective effect of N-acetylcysteine against acrylamide toxicity in liver and small and large intestine tissues. Bratisl Lek Listy 2015; 116(4): 252-8.
• 28. Helal MA. The effects of N-acetyl-L-cysteine on the female reproductive performance and nephrotoxicity in rats. Ren Fail 2016; 38(2): 311-20.
• 29. Liu J, Liu M, Ye X, Liu K, Huang J, Wang L, et al. Delay in oocyte aging in mice by the antioxidant N-acetyl-L-cysteine (NAC). Hum Reprod 2012; 27(5): 1411-20.
• 30. Hułas-Stasiak M, Dobrowolski P, Tomaszewska E, Kostro K. Maternal acrylamide treatment reduces ovarian follicle number in newborn guinea pig offspring. Reprod Toxicol. 2013; 42: 125-31.