Facteur d'impact sur 5 ans:
ISSN Imprimer: 1045-4403
ISSN En ligne: 2162-6502
Volume 30, 2020
Volume 29, 2019
Volume 28, 2018
Volume 27, 2017
Volume 26, 2016
Volume 25, 2015
Volume 24, 2014
Volume 23, 2013
Volume 22, 2012
Volume 21, 2011
Volume 20, 2010
Volume 19, 2009
Volume 18, 2008
Volume 17, 2007
Volume 16, 2006
Volume 15, 2005
Volume 14, 2004
Volume 13, 2003
Volume 12, 2002
Volume 11, 2001
Volume 10, 2000
Volume 9, 1999
Volume 8, 1998
Volume 7, 1997
Volume 6, 1996
Volume 5, 1995
Volume 4, 1994
Critical Reviews™ in Eukaryotic Gene Expression
PPAR-α Agonist Fenofibrate Ameliorates Oxidative Stress in Testicular Tissue of Diabetic Rats
Research Center of Physiology, Semnan University of Medical Sciences, Semnan, Iran
Mohammad Taghi Mohammadi
Department of Physiology and Biophysics, School of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran
Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
Halal Research Center of IRI, FDA, Tehran, Iran; Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Background: Oxidative stress has the potential to induce impotence, especially in diabetic patients. Peroxisome proliferator-activated receptor alpha (PPAR-α) agonists can potentiate antioxidants in a wide variety of tissues. However, no available evidence exists showing a direct antioxidant effect on testicular tissue in the setting of diabetes. Therefore, the aim of this study was to evaluate whether PPAR-α agonists can act directly to protect testicular tissue from oxidative damage.
Methods: Male Wistar rats (180-200 g) were randomly allocated into four groups: normal control (N), normal treated (NF), diabetic (D), and diabetic treated (DF) (n = 6 for each group). Diabetes was induced by a single intravenous injection of streptozotocin STZ (40 mg/kg). Two treatment groups (diabetic and nondiabetic) were treated with fenofibrate daily for 8 weeks (80 mg/kg orally). At the end of 8 weeks, the animals were sacrificed and blood and testicular tissue samples collected. Nitrate, malondialdehyde, and glutathione levels, and the activity of superoxide dismutase and catalase enzymes were evaluated. The data were analyzed via two-way analysis of variance (ANOVA), with P < 0.05 taken as significant.
Results: Diabetes significantly augmented free radicals, as attested by an increase in nitrate levels in testicular tissue, reduced activity of superoxide dismutase and catalase enzymes, and enhanced malondialdehyde content. These changes lead to oxidative stress in testicular tissues. Treatment with fenofibrate in the diabetic group improved oxidative stress by potentiation of antioxidant elements and a reduction in nitrate and malondialdehyde production.
Conclusion: Diabetes has a potent effect in promoting the development of oxidative damage in testicular tissue. The PPAR-a agonist fenofibrate improves the redox state and may prevent oxidative stress in the setting of diabetes-induced oxidative stress.
Yaribeygi H, Mohammadi MT, Sahebkar A. Crocin potentiates antioxidant defense system and improves oxidative damage in liver tissue in diabetic rats. Biomed Pharmacother. 2018;98:333-7.
Yaribeygi H, Panahi Y, Javadi B, Sahebkar A. The underlying role of oxidative stress in neurodegeneration: a mechanistic review. CNS Neurol Disord Drug Targets. 2018;17(3):207-15.
Newsholme P, Haber EP, Hirabara SM, Rebelato EL, Procopio J, Morgan D, Oliveira-Emilio HC, Carpinelli AR, Curi R. Diabetes associated cell stress and dysfunction: role of mitochondrial and non-mitochondrial ROS production and activity. J Physiol. 2007;583(1):9-24.
Yaribeygi H, Faghihi N, Mohammadi MT, Sahebkar A. Effects of atorvastatin on myocardial oxidative and nitrosative stress in diabetic rats. Comp Clin Pathol. 2018;27(3):691-7.
Aitken RJ, Roman SD. Antioxidant systems and oxidative stress in the testes. Oxid Med Cell Longev. 2008;1(1):15-24.
Asadi N, Bahmani M, Kheradmand A, Rafieian-Kopaei M. The impact of oxidative stress on testicular function and the role of antioxidants in improving it: a review. J Clin Diagn Res. 2017;11(5):IE01-IE05.
Choudhary R, Chawala V, Soni N, Kumar J, Vyas R. Oxidative stress and role of antioxidants in male infertility. Pak J Physiol. 2010;6(2):54-9.
Agarwal A, Virk G, Ong C, du Plessis SS. Effect of oxidative stress on male reproduction. World J Mens Health. 2014;32(1):1-17.
Sheweita SA, Tilmisany AM, Al-Sawaf H. Mechanisms of male infertility: role of antioxidants. Curr Drug Metabol. 2005;6(5):495-501.
Turner TT, Lysiak JJ. Oxidative stress: a common factor in testicular dysfunction. J Androl. 2008;29(5):488-98.
Saleh RA, Agarwal A. Oxidative stress and male infertility: from research bench to clinical practice. J Androl. 2002;23(6):737-52.
Aitken RJ, Baker MA. Causes and consequences ofapoptosis in spermatozoa; contributions to infertility and impacts on development. Int J Dev Biol. 2013;57(2-4):265-72.
Sabeur K, Ball BA. Characterization of NADPH oxidase 5 in equine testis and spermatozoa. Reproduction. 2007;134(2):263-70.
Popeijus HE. Peroxisome proliferator-activated receptor alpha (PPAR-a). In: Choi S, editor. Encyclopedia of signaling molecules. New York: Springer; 2016. p. 1-6.
Botta M, Audano M, Sahebkar A, Sirtori CR, Mitro N, Ruscica M. PPAR agonists and metabolic syndrome: an established role? Int J Mol Sci. 2018;19(4). pii:E1197.
Derosa G, Sahebkar A, Maffioli P. The role of various peroxisome proliferator-activated receptors and their ligands in clinical practice. J Cell Physiol. 2018;233(1): 153-61.
Simental-Mendia LE, Simental-Mendia M, Sanchez-Garcia A, Banach M, Atkin SL, Gotto Jr AM, Sahebkar A. Effect of fibrates on glycemic parameters: a systematic review and meta-analysis of randomized placebo-controlled trials. Pharmacol Res. 2018;132:232-41.
Derosa G, Maffioli P, Sahebkar A. Plasma uric acid concentrations are reduced by fenofibrate: a systematic review and meta-analysis of randomized placebo-controlled trials. Pharmacol Res. 2015;102:63-70.
Sahebkar A, Giua R, Pedone C, Ray KK, Vallejo-Vaz AJ, Costanzo L. Fibrate therapy and flow-mediated dilation: a systematic review and meta-analysis of randomized placebo-controlled trials. Pharmacol Res. 2016;111:163-79.
Sahebkar A, Serban MC, Mikhailidis DP, Toth PP, Muntner P, Ursoniu S, Mosterou S, Glasser S, Martin SS, Jones SR, Rizzo M, Rysz J, Sniderman AD, Pencina MJ, Banach M, Lipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group. Head-to-head comparison of statins versus fibrates in reducing plasma fibrinogen concentra-tions: a systematic review and meta-analysis. Pharmacol Res. 2016;103:236-52.
Sahebkar A, Watts GF. Fibrate therapy and circulating adiponectin concentrations: a systematic review and meta-analysis of randomized placebo-controlled trials. Atherosclerosis. 2013;230(1):110-20.
Yaribeygi H, Mohammadi MT, Sahebkar A. PPAR-a agonist improves hyperglycemia-induced oxidative stress in pancreatic cells by potentiating antioxidant defense system. Drug Res (Stuttg). 2018;68(6):355-60.
Yaribeygi H, Mohammadi MT. Evaluation of PPAR-a agonist effect on kidney performance through increment of nitric oxide during hyperglycemia-induced nephropathy in rat. Razavi Int J Med. 2016;4(2):e37670.
Yaribeygi H, Mohammadi MT, Rezaee R, Sahebkar A. Fenofibrate improves renal function by amelioration of NOX-4, IL-18, and p53 expression in an experimental model of diabetic nephropathy. J Cell Biochem. 2018;119(9):7458-69.
Sahebkar A, Hernandez-Aguilera A, Abello D, Sancho E, Camps J, Joven J. Systematic review and meta-analysis deciphering the impact of fibrates on paraoxonase-1 status. Metabolism. 2016;65(5):609-22.
Hase T, Yoshimura R, Mitsuhashi M, Segawa Y, Kawahito Y, Wada S, Nakatani T, Sano H. Expression of peroxisome proliferator-activated receptors in human testicular cancer and growth inhibition by its agonists. Urology. 2002;60(3):542-7.
Schultz R, Yan W, Toppari J, Volkl A, Gustafsson JA, Pelto-Huikko M. Expression of peroxisome proliferator-activated receptor a messenger ribonucleic acid and protein in human and rat testis. Endocrinology. 1999;140(7):2968-75.
Kadivar A, Heidari Khoei H, Hassanpour H, Ghanaei H, Golestanfar A, Mehraban H, Davoodian N, Tafti RD. Peroxisome proliferator-activated receptors (PPARa PPARg and PPARb/d) gene expression profile on ram spermatozoa and their relation to the sperm motility. Vet Res Forum. 2016;7(1):27-34.
Huang J-C. The role of peroxisome proliferator-activated receptors in the development and physiology of gametes and preimplantation embryos. PPAR Res. 2008;2008:732303.
Winterbourn CC, Hawkins RE, Brian M, Carrell RW. The estimation of red cell superoxide dismutase activity. J Lab Clin Med. 1975;85(2):337-41.
Aebi H. Catalase in vitro. Methods Enzymol. 1984; 105:121-6.
Tietze F. Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: applications to mammalian blood and other tissues. Anal Biochem. 1969;27(3):502-22.
Granger DL, Taintor RR, Boockvar KS, Hibbs Jr JB. Measurement of nitrate and nitrite in biological samples using nitrate reductase and Griess reaction. Methods Enzymol. 1996;268:142-51.
Satoh M, Fujimoto S, Haruna Y, Arakawa S, Horike H, Komai N, Sasaki T, Tsujioka K, Makino H, Kashihara N. NAD(P)H oxidase and uncoupled nitric oxide synthase are major sources of glomerular superoxide in rats with experimental diabetic nephropathy. Am J Physiol Renal Physiol. 2005;288(6):F1144-52.
Jennings P, McLaren M, Scott NA, Saniabadi AR, Belch JJ. The relationship of oxidative stress to thrombotic tendency in type 1 diabetic patients with retinopathy. Diabet Med. 1991;8(9):860-5.
Wold LE, Ceylan-Isik AF, Ren J. Oxidative stress and stress signaling: menace of diabetic cardiomyopathy. Acta Pharmacol Sin. 2005;26(8):908-17.
Zhao Y, Tan Y, Dai J, Li B, Guo L, Cui J, Wang G, Shi X, Zhang X, Mellen N, Li W, Cai L. Exacerbation of diabetes-induced testicular apoptosis by zinc deficiency is most likely associated with oxidative stress, p38 MAPK activation, and p53 activation in mice. Toxicol Lett. 2011;200(1-2):100-6.
Shrilatha B, Muralidhara. Early oxidative stress in testis and epididymal sperm in streptozotocin-induced diabetic mice: its progression and genotoxic consequences. Reprod Toxicol. 2007;23(4):578-87.
Draper H, Hadley M. Malondialdehyde determination as index of lipid peroxidation. Methods Enzymol. 1990;186:421-31.
Mallick C, Mandal S, Barik B, Bhattacharya A, Ghosh D. Protection of testicular dysfunctions by MTEC, a formulated herbal drug, in streptozotocin induced diabetic rat. Biol Pharm Bull. 2007;30(1):84-90.
Collino M, Aragno M, Mastrocola R, Benetti E, Gallicchio M, Dianzani C, Danni O, Thiemermann C, Fantozzi R. Oxidative stress and inflammatory response evoked by transient cerebral ischemia/reperfusion: effects of the PPAR-a agonist WY14643. Free Radic Biol Med. 2006;41(4):579-89.
Mehendale HM. PPAR-a: a key to the mechanism of hepatoprotection by clofibrate. Toxicol Sci. 2000;57(2):187-90.
Reddy JK, Goel SK, Nemali MR, Carrino JJ, Laffler TG, Reddy MK, Sperbeck SJ, Osumi T, Hashimoto T, Lalwani ND. Transcription regulation of peroxisomal fatty acyl-CoA oxidase and enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase in rat liver by peroxisome proliferators. Proc Natl Acad Sci U S A. 1986;83(6):1747-51.
Liu X, Jang SS, An Z, Song H, Kim WD, Yu JR, Park YW. Fenofibrate decreases radiation sensitivity via peroxisome proliferator-activated receptor a-mediated super-oxide dismutase induction in HeLa cells. Radiat Oncol J. 2012;30(2):88-95.
Ramanan S, Kooshki M, Zhao W, Hsu F-C, Robbins ME. PPARa ligands inhibit radiation-induced microglial inflammatory responses by negatively regulating NF-KB and AP-1 pathways. Free Radic Biol Med. 2008;45(12):1695-704.
Sahebkar A, Chew GT, Watts GF. New peroxisome proliferator-activated receptor agonists: potential treatments for atherogenic dyslipidemia and non-alcoholic fatty liver disease. Expert Opin Pharmacother. 2014;15(4):493-503.
Articles with similar content:
Aqueous Extracts of Cordyceps militaris (Ascomycetes) Lower the Levels of Plasma Glucose by Activating the Cholinergic Nerve in Streptozotocin-Induced Diabetic Rats
International Journal of Medicinal Mushrooms, Vol.15, 2013, issue 3
Chin-Hsien Chang, Chung-Yuh Tzeng, Yu-Wen Cheng, Hong-Chen Chen, Ying-I Chen, Yiu-Kay Lai, Tai-Hao Hsu, Yu-Chen Lee, Shih-Liang Chang, Chin-Chun Tsai
The Influence of Gingerol Treatment on Aluminum Toxicity in Rats
Journal of Environmental Pathology, Toxicology and Oncology, Vol.34, 2015, issue 1
Effect of Ginkgo biloba Extract on Lead-Induced Oxidative Stress in Different Regions of Rat Brain
Journal of Environmental Pathology, Toxicology and Oncology, Vol.34, 2015, issue 2
Prabhakara Rao Yallapragada, Manoj Kumar Velaga