1. bookVolume 54 (2020): Issue 2 (April 2020)
Journal Details
First Published
30 Mar 2016
Publication timeframe
4 times per year
access type Open Access

Can troxerutin pretreatment prevent testicular complications in prepubertal diabetic male rats?

Published Online: 08 May 2020
Volume & Issue: Volume 54 (2020) - Issue 2 (April 2020)
Page range: 85 - 95
Journal Details
First Published
30 Mar 2016
Publication timeframe
4 times per year

Objective. The vast majority of type 1 diabetes leads to a higher prevalence of reproductive system’s impairments. Troxerutin has attracted much attention owing to its favorable properties, including antihyperglycemic, anti-inflammatory, and antiapoptotic effects. This investigation was proposed to evaluate whether pretreatment with troxerutin could prevent apoptosis-induced testicular disorders in prepubertal diabetic rats.

Methods. Fifty prepubertal male Wistar rats were randomly allocated into five groups: control (C), troxerutin (TX), diabetic (D), diabetic+troxerutin (DTX), and diabetic+insulin (DI). Diabetes was induced by 55 mg/kg of streptozotocin applied intraperitoneally. In TX and DTX groups, 150 mg/kg troxerutin was administered by oral gavage. Diabetic rats in DI group received 2–4 U NPH insulin subcutaneously. Troxerutin and insulin treatments were begun immediately on the day of diabetes confirmation. After 30 days, the testicular lipid peroxidation and antioxidant activity, apoptosis process, and stereology as well as serum glucose and insulin levels were assessed.

Results. The results showed that diabetes caused a significant increase in the blood glucose, the number of TUNEL positive cells and tubules, and the malondialdehyde level as well as a significant decrease in serum insulin level compared to controls. The stereological analysis also revealed various alterations in diabetic rats compared to controls. Troxerutin treatment improved these alterations compared to the diabetic group.

Conclusion. Troxerutin-pretreatment may play an essential role in the management of the type-1 diabetes-induced testicular disorders by decreasing blood glucose and modulating apoptosis.


Abbasi Z, Tabatabaei SRF, Mazaheri Y, Barati F, Morovvati, H. Effects of sesame oil on the reproductive parameters of diabetes mellitus-induced male rats. World J Mens Health 3, 141–149, 2013.10.5534/wjmh.2013.31.2.141Search in Google Scholar

Agarwal A, Saleh RA. Role of oxidants in male infertility: rationale, significance, and treatment. Urol Clin North Am 29, 817–828, 2002.10.1016/S0094-0143(02)00081-2Search in Google Scholar

Agarwal A, Said TM. Oxidative stress, DNA damage and apoptosis in male infertility: a clinical approach. BJU Int 95, 503–507, 2005.10.1111/j.1464-410X.2005.05328.x15705068Search in Google Scholar

Aktas C, Kanter M, Erboga M, Timurkan H. Effects of experimental diabetes on testis proliferations and apoptosis in rats. J Exp Clin Med 28, 94–98, 2011.10.5835/jecm.omu.28.03.001Search in Google Scholar

Almeida SA, Kempinas WG, Lamano Carvalho TL. Sexual behavior and fertility of male rats submitted to prolonged immobilization-induced stress. Braz J Med Biol Res 33, 1105–1109, 2000.10.1590/S0100-879X200000090001910973146Search in Google Scholar

Amaral S, Moreno AJ, Santos MS, Seica R, Ramalho-Santos J. Effects of hyperglycemia on sperm and testicular cells of Goto-Kakizaki and streptozotocin-treated rat models for diabetes. Theriogenology 66, 2056–2067, 2006.10.1016/j.theriogenology.2006.06.00616860381Search in Google Scholar

Badalzadeh R, Layeghzadeh N, Alihemmati A, Mohammadi M. Beneficial effect of troxerutin on diabetes-induced vascular damages in rat aorta: histopathological alterations and antioxidation mechanism. Int J Endocrinol Metab 13, e25969, 2015.10.5812/ijem.25969438623125926856Search in Google Scholar

Badalzadeh R, Chodari L, Ghorbanzadeh V. Troxerutin, a bioflavonoid, improves oxidative stress in blood of streptozotocin-induced type-1 diabetic rats. IJPS 13, 75–86, 2017.Search in Google Scholar

Cai L, Chen S, Evans T, Deng DX, Mukherjee K, Chakrabarti S. Apoptotic germ-cell death and testicular damage in experimental diabetes: prevention by endothelin antagonism. Urol Res 28, 342–347, 2000.10.1007/s00240000013411127715Search in Google Scholar

Chandrashekar KN. Evidence of oxidative stress and mitochondrial dysfunctions in the testis of prepubertal diabetic rats. Int J Impot Res 21, 198–206, 2009.10.1038/ijir.2009.919444988Search in Google Scholar

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 35, 133–146, 2016.10.1615/JEnvironPatholToxicolOncol.201601538427481491Search in Google Scholar

Fan SH, Zhang ZF, Zheng YL, Lu J, Wu DM, Shan Q, Hu B, Wang YY. Troxerutin protects the mouse kidney from d-galactose-caused injury through anti-inflammation and anti-oxidation. Int Immunopharmacol 9, 91–96, 2009.10.1016/j.intimp.2008.10.00819000936Search in Google Scholar

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 16, 1081–1089, 2017.Search in Google Scholar

Feng SL, Li SH, Wang Y, Chen CC, Gao B. Effect of ligustrum fruit extract on reproduction in experimental diabetic rats. Asian J Androl 23, 71–73, 2001.Search in Google Scholar

Gao F, Gao E, Yue TL, Ohlstein EH, Lopez BL, Christopher TA, Ma XL. Nitric oxide mediates the antiapoptotic effect of insulin in myocardial ischemia-reperfusion: the roles of PI3-kinase, Akt, and endothelial nitric oxide synthase phosphorylation. Circulation 105, 1497–1502, 2002.10.1161/01.CIR.0000012529.00367.0F11914261Search in Google Scholar

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 387, 123–134, 2014.10.1007/s11010-013-1877-224173620Search in Google Scholar

Guneli E, Tugyan K, Ozturk H, Gumustekin M, Cilaker S, Uysal N. Effect of melatonin on testicular damage in streptozotocin-induced diabetes rats. Eur Surg Res 40, 354–360, 2008.10.1159/00011803218303272Search in Google Scholar

Hsia Y, Neubert AC, Rani F, Viner RM, Hindmarsh PC, Wong IC. An increase in the prevalence of type 1 and 2 diabetes in children and adolescents: results from prescription data from a UK general practice database. Br J Clin Pharmacol 67, 242–249, 2009.10.1111/j.1365-2125.2008.03347.x267038219260863Search in Google Scholar

Jalali M, Hassanipour M, Hajizadeh M, Khanamani Falahati Pour S, Khoshdel A, Roustai F, Rezai M, Mahmoodi M. Troxerutin chronic treatment protects against fructose-induced metabolic syndrome in male rats. IJML 4, 201–210, 2017.Search in Google Scholar

Jangir RN, Jain GC. Diabetes mellitus induced impairment of male reproductive functions: a review. Curr Diabetes Rev 10, 147–157, 2014.10.2174/157339981066614060611174524919656Search in Google Scholar

Kanter M, Aktas C, Erboga M. Protective effects of quercetin against apoptosis and oxidative stress in streptozotocin-induced diabetic rat testis. Food Chem Toxicol 50, 719–725, 2012.10.1016/j.fct.2011.11.05122166789Search in Google Scholar

Keyhanmanesh R, Hamidian G, 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 211, 63–73, 2018.10.1016/j.lfs.2018.09.01930205097Search in Google Scholar

Keyhanmanesh R, Hamidian G, Alipour MR, Oghbaei H. Beneficial treatment effects of dietary nitrate supplementation on testicular injury in Streptozotocin-induced diabetic male rats. Reprod Biomed Online 39, 357–371, 2019.10.1016/j.rbmo.2018.11.02730952494Search in Google Scholar

Kheirollahi A, Abbaszadeh A, Anbari K, Rostami B, Ahangari A, Hasanvand A, Gholami M. Troxerutin protect sperm, seminiferous epithelium and pituitary-gonadal axis from torsion-detorsion injury: An experimental study. Int J Reprod Biomed 16, 315–322, 2018.10.29252/ijrm.16.5.315Search in Google Scholar

Kianifard D, Sadrkhanlou RA, Hasanzadeh S. The ultrastructural changes of the Sertoli and Leydig cells following streptozotocin induced diabetes. Iran J Basic Med Sci 15, 623–635, 2012.Search in Google Scholar

King AJ. The use of animal models in diabetes research. Br J Pharmacol 166, 877–894, 2012.10.1111/j.1476-5381.2012.01911.x341741522352879Search in Google Scholar

Kushwaha S, Jena GB. Enalapril reduces germ cell toxicity in streptozotocin-induced diabetic rat: investigation on possible mechanisms. Naunyn Schmiedebergs Arch Pharmacol 385, 111–124, 2012.10.1007/s00210-011-0707-x22071577Search in Google Scholar

La Vignera S, Condorelli RA, Di Mauro M, Lo Presti D, Mongioi LM, Russo G, Calogero AE. Reproductive function in male patients with type 1 diabetes mellitus. Andrology 3, 1082–1087, 2015.10.1111/andr.1209726446574Search in Google Scholar

Lu YX, Zhang Q, Li J, Sun YX, Wang LY, Cheng WM, Hu XY. Antidiabetic effects of total flavonoids from Litsea Coreana leve on fat-fed, streptozotocin-induced type 2 diabetic rats. Am J Chin Med 38, 713–725, 2010.10.1142/S0192415X1000818420626057Search in Google Scholar

Mokhtari B, Badalzadeh R, Alihemmati A, Mohammadi M. Phosphorylation of GSK-3β and reduction of apoptosis as targets of troxerutin effect on reperfusion injury of diabetic myocardium. Eur J Pharmacol 765, 316–321, 2015.10.1016/j.ejphar.2015.08.05626341011Search in Google Scholar

Muller D, Jones PM, Persaud SJ. Autocrine anti-apoptotic and proliferative effects of insulin in pancreatic β-cells. FEBS Lett 580, 6977–6980, 2006.10.1016/j.febslet.2006.11.06617161395Search in Google Scholar

Naderi R, Mohaddes G, Mohammadi M, Ghaznavi R, Ghyasi R, Vatankhah AM. Voluntary exercise protects heart from oxidative stress in diabetic rats. Adv Pharm Bull 5, 231–236, 2015.10.15171/apb.2015.032451709326236662Search in Google Scholar

Oghbaei H, Asl NA, Sheikhzadeh F. Can regular moderate exercise lead to changes in miRNA-146a and its adapter proteins in the kidney of streptozotocin-induced diabetic male rats? Endocr Regul 51, 145–152, 2017.10.1515/enr-2017-001528858844Search in Google Scholar

Oghbaei H, Alipour MR, Hamidian G, Ahmadi M, Ghorbanzadeh V, Keyhanmanesh R. Two months sodium nitrate supplementation alleviates testicular injury in streptozotocin-induced diabetic male rats. Exp Physiol 103, 1603–1617, 2018.10.1113/EP08719830088840Search in Google Scholar

Oghbaei H, Alipour MR, Mohaddes G, Hamidian GR, Keyhanmanesh R. Evaluation of ameliorative effect of sodium nitrate in experimental model of streptozotocin-induced diabetic neuropathy in male rats. Endocr Regul 53, 14–25, 2019.10.2478/enr-2019-000331517620Search in Google Scholar

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 194, 32–45, 2016.10.1016/j.foodchem.2015.07.07826471524Search in Google Scholar

Pari L, Monisha P, Mohamed Jalaludeen A. Beneficial role of diosgenin on oxidative stress in aorta of streptozotocin induced diabetic rats. Eur J Pharmacol 691, 143–150, 2012.10.1016/j.ejphar.2012.06.03822771295Search in Google Scholar

Pourmemar E, Majdi A, Haramshahi M, Talebi M, Karimi P, Sadigh-Eteghad S. Intranasal cerebrolysin attenuates learning and memory impairments in D-galactose-induced senescence in mice. Exp Gerontol 87, 16–22, 2017.10.1016/j.exger.2016.11.01127894939Search in Google Scholar

Sampath S, Karundevi B. Effect of troxerutin on insulin signaling molecules in the gastrocnemius muscle of high fat and sucrose-induced type-2 diabetic adult male rat. Mol Cell Biochem 395, 11–27, 2014.10.1007/s11010-014-2107-224880482Search in Google Scholar

Shrilatha B, Muralidhara. Occurrence of oxidative impairments, response of antioxidant defences and associated biochemical perturbations in male reproductive milieu in the Streptozotocin-diabetic rat. Int J Androl 30, 508–518, 2007.10.1111/j.1365-2605.2007.00748.x17573857Search in Google Scholar

Soudamani S, Malini T, Balasubramanian K. Effects of streptozotocin-diabetes and insulin replacement on the epididymis of prepubertal rats: histological and histomorphometric studies. Endocr Res 31, 81–98, 2005.10.1080/0743580050022919316353669Search in Google Scholar

Wu XH, Yang SH, Duan DY, Cheng HH, Bao YT, Zhang Y. Anti-apoptotic effect of insulin in the control of cell death and neurologic deficit after acute spinal cord injury in rats. J Neurotrauma 24, 1502–1512, 2007.10.1089/neu.2006.022817892411Search in Google Scholar

Yaghoubi A, Shahedi A, Akbari H, Nematollahi-Mahani SN. Do insulin replacement and omega3 protect the male reproductive function of the streptozotocin-induced diabetic mice? J Nutr Metab 2017, 6102985, 2017.10.1155/2017/6102985552318728770110Search in Google Scholar

Yu Y, Zheng G. Troxerutin protects against diabetic cardiomyopathy through NF-κB/AKT/IRS1 in a rat model of type 2 diabetes. Mol Med Rep 15, 3473–3478, 2017.10.3892/mmr.2017.6456543628428440404Search in Google Scholar

Zhang ZF, Shan Q, Zhuang J, Zhang YQ, Wang X, Fan SH, Lu J, Wu DM, Hu B, Zheng YL. Troxerutin inhibits 2, 2’, 4, 4’-tetrabromodiphenyl ether (BDE-47)-induced hepatocyte apoptosis by restoring proteasome function. Toxicol Lett 233, 246–257, 2015.10.1016/j.toxlet.2015.01.01725639565Search in Google Scholar

Zhang S, Yuan L, Zhang L, Li C, Li J. Prophylactic use of Troxerutin can delay the development of diabetic cognitive dysfunction and improve the expression of Nrf2 in the hippocampus on STZ diabetic rats. Behav Neurol 2018, 8678539, 2018.10.1155/2018/8678539592513729849815Search in Google Scholar

Zhao Y, Tan Y, Dai J, Li B, Guo L, Cui J, Wang G, Shi X, Zhang X, Mellen N, Li W. 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 200, 100–106, 2011.10.1016/j.toxlet.2010.11.00121078376Search in Google Scholar

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