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Shokri, A., Pourheydar, B., Farjah, G. H., Krimipour, M., & Pourheydar, M. (2023). Effects of glibenclamide and troxerutin on the sperm parameters and histopathological changes of testis in streptozotocin-induced diabetic male rats: An experimental study. International Journal of Reproductive BioMedicine (IJRM), 21(2), 123–138. https://doi.org/10.18502/ijrm.v21i2.12803
https://doi.org/10.18502/ijrm.v21i2.12803
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authors
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Aynaz Shokri
Aynaz Shokri
Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran.
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Bagher Pourheydar
Bagher Pourheydar
Neurophysiology Research Center, Department of Anatomical Sciences, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran.
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Gholam Hossein Farjah
Gholam Hossein Farjah
europhysiology Research Center, Department of Anatomical Sciences, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran.
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Mojtaba Krimipour
Mojtaba Krimipour
Department of Anatomical Sciences, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran.
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Maryam Pourheydar
Maryam Pourheydar
Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran.
Published Date
- Mar 9, 2023
Effects of glibenclamide and troxerutin on the sperm parameters and histopathological changes of testis in streptozotocin-induced diabetic male rats: An experimental study
Abstract
Background: Oxidative stress is a major contributor to diabetes mellitus (DM), which leads to testicular damage and infertility. Objective: The aim of this study was to investigate the effects of glibenclamide (GL) as a chemical medicine and troxerutin (TR) as an herbal agent on sperm parameters and histopathological changes of testis in diabetic male rats.
Materials and Methods: Forty male Wistar rats (230-260 gr) were randomly divided into 5 groups (n = 8/each), including control, diabetic (D), GL, TR, and GL+TR. DM was induced by the administration of 60 mg/kg streptozotocin intraperitoneally. The groups were treated with 5 mg/kg/day of GL or 150 mg/kg/day of TR via oral gavage for 4 wk. In the final stage of the treatment, blood sampling was done for biochemical analysis. The rats were then sacrificed and their left testis and epididymis were dissected for sperm analysis, histopathology, and morphometric assessment.
Results: A significant decrease in the number, motility, viability, maturity, and chromatin quality of sperm was found in diabetic rats compared to control group. (p < 0.001). DM also increased the malondialdehyde level and decreased the level of the serum’s total antioxidant capacity compared to the control group (p < 0.001). Furthermore, we observed a significant difference in seminiferous tubule diameter, germinal epithelium height, and testicular histological abnormalities in diabetic rats compared to control group (p < 0.001). Administration of GL, TR, and their combination improved the abovementioned parameters, and treatment with TR provided a higher improvement (p < 0.001).
Conclusion: According to these findings, it can be concluded that TR plays a more influential role than GL to treat diabetic-induced infertility.
Key words: Diabetes, Glibenclamide, Sperm, Testis, Troxerutin.
References
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[3] Rovira-Llopis S, Bañuls C, de Marañon AM, Diaz- Morales N, Jover A, Garzon S, et al. Low testosterone levels are related to oxidative stress, mitochondrial dysfunction and altered subclinical atherosclerotic markers in type 2 diabetic male patients. Free Radic Biol Med 2017; 108: 155–162.
[4] Roshankhah SH, Salahshoor MR, Aryanfar S, Jalili F, Sohrabil M, Jalili C, et al. Effects of curcumin on sperm parameters abnormalities induced by morphine in rat. J Med Biomed Sci 2017; 6: 1–10.
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[13] Singh B, Singh A, Kumar V. Ameliorative effect of adjunct therapy of metformin with atorvastatin on streptozotocin-induced diabetes mellitus in rats. Drug Res 2016; 66: 28–32.
[14] Qadiri A, Bavil FM, Hamidian Gh, Oskuye ZZ, Ahmadi M, Oghbaei H, et al. Administration of troxerutin improves testicular function and structure in type-1 diabetic adult rats by reduction of apoptosis. Avicenna J Phytomed 2019; 9: 374–385.
[15] Abdelhafez HM, Abu-Amara TMM, El-debsi SM. Evaluation of role of glibenclamide and Aphanizomenon flos-aquae extract on lymph node and spleen of diabetic Rats. Egypt J Hosp Med 2015; 61: 700–720.
[16] Elangovan P, Jalaludeen AM, Ramakrishnan R, Pari L. Protective effect of troxerutin on nickel-induced testicular toxicity in wistar rats. J Environ Pathol Toxicol Oncol 2016; 35: 133–146.
[17] Shokri S, Hemadi M, Bayat G, Bahmanzadeh M, Jafari-Anarkooli I, Mashkani Β. Combination of running exercise and high dose of anabolic androgenic steroid, nandrolone decanoate, increases protamine deficiency and DNA damage in rat spermatozoa. Andrologia 2014; 46: 184–190.
[18] World Health Organization. WHO laboratory manual for the examination and processing of human semen. 5th Ed. Switzerland, World Health Organization Press; 2010.
[19] Mirzaei Khorramabadi K, Talebi AR, Abbasi Sarcheshmeh A, Mirjalili A. Protective effect of vitamin E on oxidative stress and sperm apoptosis in diabetic Mice. Int J Reprod BioMed 2019; 17: 127–134.
[20] Mortazavi M, Salehi I, Alizadeh Z, Vahabian M, Mohammadi Roushandeh A. Protective effects of antioxidants on sperm parameters and seminiferous tubules epithelium in high fat-fed rats. J Reperod Infertil 2014; 15: 22–28.
[21] Mardanshahi T, Rezaei N, Zare Z, Malekzadeh Shafaroudi M, Mohammadi H. Effects of L-Carnitine on the sperm parameters disorders, apoptosis of spermatogenic cells and testis histopathology in diabetic Rats. Int J Reprod BioMed 2019; 17: 325–336.
[22] Zhu B, Zheng Y-F, Zhang Y-Y, Cao Y-S, Zhang L, Li X-G, et al. Protective effect of L-carnitine in cyclophosphamide-induced germ cell apoptosis. J Zhejiang Univ Sci B 2015; 16: 780–787.
[23] Li M-W, Kent Lloyd KC. DNA fragmentation index (DFI) as a measure of sperm quality and fertility in mice. Sci Rep 2020; 10: 3833.
[24] Oskuye ZZ, Bavil FM, Hamidian GR, Mehri K, Qadiri A, Ahmadi M, et al. Troxerutin affects the male fertility in prepubertal type 1 diabetic male rats. Iran J Basic Med Sci 2019; 22: 197–205.
[25] Keyhanmanesh R, Hamidian Gh, Alipour MR, Ranjbar M, Oghbaei H. Protective effects of sodium nitrate against testicular apoptosis and spermatogenesis impairments in streptozotocin-induced diabetic male rats. Life Sci 2018; 211: 63–73.
[26] Asmat U, Abad K, Ismail K. Diabetes mellitus and oxidative stress-A concise review. Saudi Pharm J 2016; 24: 547–553.
[27] Omolaoye T, Du Plessis SS. Diabetes mellitus and male infertility. Asian Pac J Reprod 2018; 7: 6–14.
[28] Alotaibi MR, Fatani AJ, Almnaizel AT, Ahmed MM, Abuohashish HM, Al-Rejaie S, et al. In vivo assessment of combined effects of glibenclamide and losartan in diabetic rats. Med Princ Pract 2019; 28: 178–185.
[29] Sarkar P, Nath K, Banu S. Modulatory effect of baicalein on gene expression and activity of antioxidant enzymes in streptozotocin-nicotinamide induced diabetic rats. Braz J Pharm Sci 2019; 55: e18201.
[30] Dadpisheh S, Ahmadvand H, Jafaripour L, Nouryazdan N, Shati H, Bagheri Sh. Effect of troxerutin on oxidative stress induced by sciatic nerve ischemia-reperfusion injury in rats. J Kerman Univ Medical Sci 2020; 27: 338– 347.
[31] Farajdokht F, Amani M, Bavil FM, Alihemmati A, Mohaddes G, Babri S. Troxerutin protects hippocampal neurons against amyloid beta-induced oxidative stress and apoptosis. EXCLI J 2017; 16: 1081–1089.
[32] Mokhtari B, Badalzadeh R, Alihemmati A, Mohammadi M. Phosphorylation of GSK-3β and reduction of apoptosis as targets of tro xerutin effect on reperfusion injury of diabetic myocardium. Eur J Pharmacol 2015; 765: 316–321.
[33] Ahmadi R, Pishghadam S, Mollaamine F, Zand Monfared MR. Comparing the effects of ginger and glibenclamide on dihydroxybenzoic metabolites produced in STZ-induced diabetic rats. Int J Endocrinol Metab 2013; 11: e10266.
[2] Niwas Jangir R, Chand Jain G. Diabetes mellitus induced impairment of male reproductive functions: A review. Curr Diabetes Rev 2014; 10: 147–157.
[3] Rovira-Llopis S, Bañuls C, de Marañon AM, Diaz- Morales N, Jover A, Garzon S, et al. Low testosterone levels are related to oxidative stress, mitochondrial dysfunction and altered subclinical atherosclerotic markers in type 2 diabetic male patients. Free Radic Biol Med 2017; 108: 155–162.
[4] Roshankhah SH, Salahshoor MR, Aryanfar S, Jalili F, Sohrabil M, Jalili C, et al. Effects of curcumin on sperm parameters abnormalities induced by morphine in rat. J Med Biomed Sci 2017; 6: 1–10.
[5] Ghanbari E, Nejati V, Azadbakht M. Protective effect of royal jelly against renal damage in streptozotocin-induced diabetic rats. Iranian Journal of Toxicology 2015; 9: 1258–1263.
[6] Rani M, Yadav S, Choudhary S, Sharma S, Pandey SM. Incidence of hypoglycemia and other side effects in patients of type 2 diabetes mellitus treated with glimepiride versus glibenclamide. Int J Health Sci Res 2014; 4: 68–72.
[7] Panat NA, Maurya DK, Ghaskadbi SS, Sandur SK. Troxerutin, a plant flavonoid, protects cells against oxidative stress-induced cell death through radical scavenging mechanism. Food Chem 2016; 194: 32–45.
[8] Yu Y, Zheng G. Troxerutin protects against diabetic cardiomyopathy through NFκB/AKT/IRS1 in a rat model of type 2 diabetes. Mol Med Rep 2017; 15: 3473–3478.
[9] Lu J, Wu D-M, Zheng Y-L, Hu B, Cheng W, Zhang ZF, et al. Troxerutin counteracts domoic acid-induced memory deficits in mice by inhibiting CCAAT/enhancer binding protein β–mediated inflammatory response and oxidative stress. J Immunol 2013; 190: 3466–3479.
[10] Zamanian M, Hajizadeh MR, Esmaeili Nadimi A, Shamsizadeh A, Allahtavakoli M. Antifatigue effects of troxerutin on exercise endurance capacity, oxidative stress and matrix metalloproteinase-9 levels in trained male rats. Fundam Clin Pharmacol 2017; 31: 447–455.
[11] Vinothkumar R, Kumar RV, Sudha M, Viswanathan P, Balasubramanian T, Nalini N. Modulatory effect of troxerutin on biotransforming enzymes and preneoplasic lesions induced by 1, 2-dimethylhydrazine in rat colon carcinogenesis. Exp Mol Pathol 2014; 96: 15–26.
[12] Geetha R, Yogalakshmi B, Sreeja S, Bhavani K, Anuradha CV. Troxerutin suppresses lipid abnormalities in the heart of high-fat-high-fructose diet-fed mice. Mol Cell Biochem 2014; 387: 123–134.
[13] Singh B, Singh A, Kumar V. Ameliorative effect of adjunct therapy of metformin with atorvastatin on streptozotocin-induced diabetes mellitus in rats. Drug Res 2016; 66: 28–32.
[14] Qadiri A, Bavil FM, Hamidian Gh, Oskuye ZZ, Ahmadi M, Oghbaei H, et al. Administration of troxerutin improves testicular function and structure in type-1 diabetic adult rats by reduction of apoptosis. Avicenna J Phytomed 2019; 9: 374–385.
[15] Abdelhafez HM, Abu-Amara TMM, El-debsi SM. Evaluation of role of glibenclamide and Aphanizomenon flos-aquae extract on lymph node and spleen of diabetic Rats. Egypt J Hosp Med 2015; 61: 700–720.
[16] Elangovan P, Jalaludeen AM, Ramakrishnan R, Pari L. Protective effect of troxerutin on nickel-induced testicular toxicity in wistar rats. J Environ Pathol Toxicol Oncol 2016; 35: 133–146.
[17] Shokri S, Hemadi M, Bayat G, Bahmanzadeh M, Jafari-Anarkooli I, Mashkani Β. Combination of running exercise and high dose of anabolic androgenic steroid, nandrolone decanoate, increases protamine deficiency and DNA damage in rat spermatozoa. Andrologia 2014; 46: 184–190.
[18] World Health Organization. WHO laboratory manual for the examination and processing of human semen. 5th Ed. Switzerland, World Health Organization Press; 2010.
[19] Mirzaei Khorramabadi K, Talebi AR, Abbasi Sarcheshmeh A, Mirjalili A. Protective effect of vitamin E on oxidative stress and sperm apoptosis in diabetic Mice. Int J Reprod BioMed 2019; 17: 127–134.
[20] Mortazavi M, Salehi I, Alizadeh Z, Vahabian M, Mohammadi Roushandeh A. Protective effects of antioxidants on sperm parameters and seminiferous tubules epithelium in high fat-fed rats. J Reperod Infertil 2014; 15: 22–28.
[21] Mardanshahi T, Rezaei N, Zare Z, Malekzadeh Shafaroudi M, Mohammadi H. Effects of L-Carnitine on the sperm parameters disorders, apoptosis of spermatogenic cells and testis histopathology in diabetic Rats. Int J Reprod BioMed 2019; 17: 325–336.
[22] Zhu B, Zheng Y-F, Zhang Y-Y, Cao Y-S, Zhang L, Li X-G, et al. Protective effect of L-carnitine in cyclophosphamide-induced germ cell apoptosis. J Zhejiang Univ Sci B 2015; 16: 780–787.
[23] Li M-W, Kent Lloyd KC. DNA fragmentation index (DFI) as a measure of sperm quality and fertility in mice. Sci Rep 2020; 10: 3833.
[24] Oskuye ZZ, Bavil FM, Hamidian GR, Mehri K, Qadiri A, Ahmadi M, et al. Troxerutin affects the male fertility in prepubertal type 1 diabetic male rats. Iran J Basic Med Sci 2019; 22: 197–205.
[25] Keyhanmanesh R, Hamidian Gh, Alipour MR, Ranjbar M, Oghbaei H. Protective effects of sodium nitrate against testicular apoptosis and spermatogenesis impairments in streptozotocin-induced diabetic male rats. Life Sci 2018; 211: 63–73.
[26] Asmat U, Abad K, Ismail K. Diabetes mellitus and oxidative stress-A concise review. Saudi Pharm J 2016; 24: 547–553.
[27] Omolaoye T, Du Plessis SS. Diabetes mellitus and male infertility. Asian Pac J Reprod 2018; 7: 6–14.
[28] Alotaibi MR, Fatani AJ, Almnaizel AT, Ahmed MM, Abuohashish HM, Al-Rejaie S, et al. In vivo assessment of combined effects of glibenclamide and losartan in diabetic rats. Med Princ Pract 2019; 28: 178–185.
[29] Sarkar P, Nath K, Banu S. Modulatory effect of baicalein on gene expression and activity of antioxidant enzymes in streptozotocin-nicotinamide induced diabetic rats. Braz J Pharm Sci 2019; 55: e18201.
[30] Dadpisheh S, Ahmadvand H, Jafaripour L, Nouryazdan N, Shati H, Bagheri Sh. Effect of troxerutin on oxidative stress induced by sciatic nerve ischemia-reperfusion injury in rats. J Kerman Univ Medical Sci 2020; 27: 338– 347.
[31] Farajdokht F, Amani M, Bavil FM, Alihemmati A, Mohaddes G, Babri S. Troxerutin protects hippocampal neurons against amyloid beta-induced oxidative stress and apoptosis. EXCLI J 2017; 16: 1081–1089.
[32] Mokhtari B, Badalzadeh R, Alihemmati A, Mohammadi M. Phosphorylation of GSK-3β and reduction of apoptosis as targets of tro xerutin effect on reperfusion injury of diabetic myocardium. Eur J Pharmacol 2015; 765: 316–321.
[33] Ahmadi R, Pishghadam S, Mollaamine F, Zand Monfared MR. Comparing the effects of ginger and glibenclamide on dihydroxybenzoic metabolites produced in STZ-induced diabetic rats. Int J Endocrinol Metab 2013; 11: e10266.