Effects of coenzyme Q10 and N-acetylcysteine on the expression of apoptotic biomarkers and histopathological findings in the permethrin-induced hepatotoxicity in rats

Document Type : Research Paper

Authors

1 1Students' Research Committee, Baqiyatallah University of Medical Sciences, Tehran, Iran

2 Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran

3 Department of Biology, Faculty of Basic Sciences, Rasht Branch, Islamic Azad University, Rasht, Iran

4 4Department of Pharmacology and Toxicology, Faculty of Pharmacy, Baqiyatallah University of Medical Sciences, Tehran, Iran

5 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Baqiyatallah University of Medical Sciences, Tehran, Iran

10.22124/cjes.2023.7254

Abstract

Permethrin (PMT) is a synthetic pyrethroid insecticide widely applied in the agriculture and animal husbandry industry. The current study focused on the evaluation of the oxidative damage and apoptosis induced by PMT, as well as the protective role of coenzyme Q10 and N-acetylcysteine (NAC) against PMT toxicity in the liver of male rats. In this study,  rats were divided in four groups, including G1 (control), G2 (PMT), G3 (NAC + PMT), and G4 (Q10 + PMT). Levels of malondialdehyde (MDA) and total antioxidant capacity (TAC) were measured. RT-PCR was adopted to study the expression of Bax, Bcl2, p53, Caspases-3 and -9 genes. PMT exposure significantly decreased FRAP value, whereas increased MDA content in the liver tissue (p < 0.001). While Bcl2 was downregulated (5.31-fold), permethrin increased the expression of Bax (4.84-fold), p53 (4.67-fold), Caspases-3 (6.21-fold) and Caspases -9 (6.36-fold) genes in exposed group (p<0.001). Both Q10 and NAC significantly improved FRAP values and decreased MDA level. Unlike the apoptotic genes, Bcl2 expression was significantly reversed after NAC and Q10 therapy (p < 0.001). In conclusion, PMT exposure induced oxidative stress and liver cells’ apoptosis. Q10 and NAC can mitigate toxic effects of PMT and consequently protect liver damage.

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Al-badry, FAM 2022, Physiological disturbances and histological damages of reproductive system in male rats resulted by metformin. Caspian Journal of Environmental Sciences, 20: 739-746.
Benzie, IFF 1996, Lipid peroxidation: A review of causes, consequences, measurement and dietary influences. International Journal of Food Sciences and Nutrition, 47: 233-261.
Colagar, AH, Marzony, ET & Chaichi, MJ 2009, Zinc levels in seminal plasma are associated with sperm quality in fertile and infertile men. Nutrition Research, 29: 82-88.
Crane, FL 2001, Biochemical functions of coenzyme Q10. Journal of the American College of Nutrition, 20: 591-598.
Drago, B, Shah, NS & Shah, SH 2014, Acute permethrin neurotoxicity: Variable presentations, high index of suspicion. Toxicology Reports, 1 : 1026-1028.
Dymond, NL & Swift, IM 2008, Permethrin toxicity in cats: a retrospective study of 20 cases. Australian Veterinary Journal, 86: 219-223.
Fan, L, Feng, Y, Chen, GC, Qin, LQ, Fu, CL & Chen, LH 2017, Effects of coenzyme Q10 supplementation on inflammatory markers: A systematic review and meta-analysis of randomized controlled trials. Pharmacological Research, 119: 128-136.
Fuller, B, Smith, D, Howerton, A & Kern, D 2006, Anti‐inflammatory effects of CoQ10 and colorless carotenoids. Journal of Cosmetic Dermatology, 5: 30-38.
Gabbianelli, R, Falcioni, ML, Nasuti, C, Cantalamessa, F, Imada, I & Inoue, M 2009, Effect of permethrin insecticide on rat polymorphonuclear neutrophils. Chemico-Biological Interactions, 182: 245-252.
Garrido-Maraver, J, Cordero, MD, Oropesa-Ávila, M, Fernandez Vega, A, de la Mata, M, Delgado Pavon, A, de Miguel, M, Perez Calero, C, Villanueva Paz, M, Cotan, D & Sanchez-Alcazar, JA 2014 Coenzyme Q10 therapy. Molecular Syndromology, 5: 187-197.
Guvenc, D, Kabak, YB, Atmaca, E, Aksoy, A & Guvenc, T 2013, Examination of caspase-dependent apoptotic and necrotic changes in rat kidney exposed to different doses of permethrin. Biotechnic & Histochemistry, 88: 76-85.
Harchegani, AB, Dahan, H, Tahmasbpour, E & Shahriary, A 2018, Effects of zinc deficiency on impaired spermatogenesis and male infertility: the role of oxidative stress, inflammation and apoptosis. Human Fertility.
Kotil, T & Yön, ND 2015, The effects of permethrin on rat ovarian tissue morphology. Experimental and Toxicologic Pathology, 67: 279-285.
Larki, RA, Zayerzadeh, E, Harzandi, N & Anissian, A 2020, Protective effects of Echium amoenum on oxidative stress and gene expression induced by Permethrin in Wistar rats. Hepatitis Monthly, 20(6).
Ma, Z, Chu, L, Liu, H, Wang, W, Li, J, Yao, W, Yi, J & Gao, Y 2017, Beneficial effects of paeoniflorin on non-alcoholic fatty liver disease induced by high-fat diet in rats. Scientific Reports, 7: 44819.
Mozhdeganloo, Z, Jafari, AM, Koohi, MK & Heidarpour, M 2016, Permethrin-induced oxidative damage in liver of rainbow trout (Oncorhynchus mykiss) and its attenuation by vitamin C. Iranian Journal of Veterinary Research, 17: 31.
Palipoch, S 2013 A review of oxidative stress in acute kidney injury: protective role of medicinal plants-derived antioxidants. African Journal of Traditional, Complementary and Alternative Medicines, 10: 88-93.
Parpieva, MJ, Mirkhamidova, P, Pozilov, MK, Alimova, RA 2023, Effects of sophoroflavonoside and narcissin flavonoids on the amount of malondialdehyde, a product of lipid peroxidation, and the activity of the enzyme cytochrome c oxidase in rat liver mitochondria poisoned with indoxacarb pesticide. Caspian Journal of Environmental Sciences, 21: 997-1000.
Prater, MR, Gogal Jr, RM, Blaylock, BL, Longstreth, J & Holladay, SD 2002, Single-dose topical exposure to the pyrethroid insecticide, permethrin in C57BL/6N mice: effects on thymus and spleen. Food and Chemical Toxicology, 40: 1863-1873.
Rao, B, Soufir, JC, Martin, M & David, G 1989, Lipid peroxidation in human spermatozoa as related to midpiece abnormalities and motility. Gamete Research, 24: 127-134.
Sadat, U 2014, N-acetylcysteine in contrast-induced acute kidney injury: Clinical use against principles of evidence-based clinical medicine. Expert Review of Cardiovascular Therapy, 12: 1-3.
Schmelzer, C, Lindner, I, Rimbach, G, Niklowitz, P, Menke, T & Döring, F 2008, Functions of coenzyme Q10 in inflammation and gene expression. Biofactors, 32: 179-183.
Shimizu, MHM, Gois, PHF, Volpini, RA, Canale, D, Luchi, WM, Froeder, L, Pfeferman Heilberg, I & Seguro, AC 2017, N-acetylcysteine protects against star fruit-induced acute kidney injury. Renal Failure, 39: 193-202.
Sifuentes-Franco, S, Sánchez-Macías, DC, Carrillo-Ibarra, S, Rivera-Valdés, JJ, Zuñiga, LY & Sánchez-López, VA, 2022, Antioxidant and anti-inflammatory effects of coenzyme Q10 supplementation on infectious diseases. Healthcare 10: 487.
Wang, HZ, Peng, ZY, Wen, XY, Rimmele, T, Bishop, JV & Kellum, JA 2011 N-acetylcysteine is effective for prevention but not for treatment of folic acid-induced acute kidney injury in mice. Critical Care Medicine, 39: 2487.