Beneficial effects of Lycium barbarum polysaccharide on spermatogenesis by improving antioxidant activity and inhibiting apoptosis in streptozotocin-induced diabetic male mice.

Spermatogenic dysfunction is one of the major secondary complications of diabetes. L. barbarum polysaccharide (LBP) has long been considered to possess anti-apoptotic activities and antioxidant, anti-inflammatory and fertility-enhancing properties in traditional medical practices in China. The aim of the current study was to seek out scientific evidence to determine if LBP also contributes to the recovery from spermatogenic dysfunction in diabetic individuals. We investigated whether the oral administration of LBP in streptozotocin (STZ)-induced type-1 diabetic male mice would reverse spermatogenic dysfunction and improve histological damage in testes. After the oral administration of LBP (10, 20 or 40 mg kg-1, respectively), sildenafil citrate (5 mg kg-1) or saline for 62 consecutive days, the sperm parameters were analyzed. Macroscopic and microscopic changes in the reproductive organs, including their weight, and photomicroscope and electronmicroscope images were also assessed. In addition, the antioxidant capacity and levels of malondialdehyde in the testes were determined according to the instructions provided with the assay kits and the expression of the apoptosis-related proteins, Caspase-3, Bax and Bcl-2, in the testes was analyzed using western-blot analysis. LBP treatment of diabetic mice considerably recovered the sperm parameters, increased the weight of the reproductive organs, ameliorated their histological appearance and increased antioxidant enzyme activity to different degrees. Moreover, our data also showed a marked decrease in Caspase-3 expression and an increase in the ratio of Bcl-2/Bax 43 after LBP administration (40 mg kg-1) when compared to the diabetic group. These results demonstrate that LBP exerts protective effects on diabetes induced male spermatogenic dysfunction, which is likely to be mediated through increasing antioxidant enzyme activities and inhibiting cell death.

[1]  E. Rashed,et al.  Anti-apoptotic and antioxidant effects of low dose gamma irradiation against diabetes-induced brain injury in rats , 2016, Radiation and environmental biophysics.

[2]  G. Türk,et al.  Effect of etodolac hydrazone, a new compound synthesised from etodolac, on spermatozoon quality, testicular lipid peroxidation, apoptosis and spermatozoon DNA integrity , 2016, Andrologia.

[3]  M. Blettner,et al.  Obituary William F. Morgan (23 December 1952–13 November 2015) , 2016, Radiation and environmental biophysics.

[4]  Mohammed Naseeruddin Inamdar,et al.  Antioxidant Potential and Ability of Phloroglucinol to Decrease Formation of Advanced Glycation End Products Increase Efficacy of Sildenafil in Diabetes-Induced Sexual Dysfunction of Rats , 2016, Sexual medicine.

[5]  A. Hamza,et al.  Rosuvastatin ameliorates diabetes-induced reproductive damage via suppression of oxidative stress, inflammatory and apoptotic pathways in male rats. , 2015, Life sciences.

[6]  M. Afifi,et al.  Ameliorative Effect of Zinc Oxide Nanoparticles on Antioxidants and Sperm Characteristics in Streptozotocin-Induced Diabetic Rat Testes , 2015, BioMed research international.

[7]  Jian-Qiang Yu,et al.  Oxymatrine attenuated hypoxic-ischemic brain damage in neonatal rats via improving antioxidant enzyme activities and inhibiting cell death , 2015, Neurochemistry International.

[8]  R. Aitken,et al.  Oxidative stress and human spermatozoa: diagnostic and functional significance of aldehydes generated as a result of lipid peroxidation. , 2015, Molecular human reproduction.

[9]  C. Kaito,et al.  Antibiotic-producing bacteria from stag beetle mycangia. , 2015, Drug Discoveries & Therapeutics.

[10]  Emanuela Locci,et al.  Monitoring the Modifications of the Vitreous Humor Metabolite Profile after Death: An Animal Model , 2015, BioMed research international.

[11]  Shu-Feng Zhou,et al.  An evidence-based update on the pharmacological activities and possible molecular targets of Lycium barbarum polysaccharides , 2014, Drug design, development and therapy.

[12]  S. De Flora,et al.  Effect of cigarette smoke on DNA damage, oxidative stress, and morphological alterations in mouse testis and spermatozoa. , 2015, International journal of hygiene and environmental health.

[13]  A. Bansal,et al.  Emerging potential of citrus flavanones as an antioxidant in diabetes and its complications. , 2015, Current topics in medicinal chemistry.

[14]  C. Onah,et al.  The levels of testosterone, zinc, manganese and selenium in type 2 diabetic patient in South-Eastern Nigeria - , 2015 .

[15]  H. Heidari,et al.  Effects of Hydro-Alcoholic Extract of Rhus coriaria (Sumac) Seeds on Reproductive Complications of Nicotinamide-Streptozotocin Induced Type-2 Diabetes in Male Mice , 2014, The world journal of men's health.

[16]  L. Rochette,et al.  Diabetes, oxidative stress and therapeutic strategies. , 2014, Biochimica et biophysica acta.

[17]  Z. Xin,et al.  Prophylactic Protective Effects and Its Potential Mechanisms of IcarisideII on Streptozotocin Induced Spermatogenic Dysfunction , 2014, International journal of molecular sciences.

[18]  Mohammed Naseeruddin Inamdar,et al.  Efficacy of ellagic acid and sildenafil in diabetes-induced sexual dysfunction , 2014, Pharmacognosy magazine.

[19]  Xiao Cui,et al.  The effect of Lycium barbarum polysaccharides on the male rats׳ reproductive system and spermatogenic cell apoptosis exposed to low-dose ionizing irradiation. , 2014, Journal of ethnopharmacology.

[20]  K. Moley,et al.  Leptin monotherapy rescues spermatogenesis in male Akita type 1 diabetic mice. , 2014, Endocrinology.

[21]  A. Agarwal,et al.  Effect of Oxidative Stress on Male Reproduction , 2014, The world journal of men's health.

[22]  Silas W Smith,et al.  An approach to chemotherapy-associated toxicity. , 2014, Emergency medicine clinics of North America.

[23]  Xinghua Zhao,et al.  Protective Effects of Lycium barbarum Polysaccharides on Testis Spermatogenic Injury Induced by Bisphenol A in Mice , 2013, Evidence-based complementary and alternative medicine : eCAM.

[24]  G. Ghirlanda,et al.  Oxidative Stress in Diabetes: Implications for Vascular and Other Complications , 2013, International journal of molecular sciences.

[25]  M. Kanter,et al.  Curcumin attenuates testicular damage, apoptotic germ cell death, and oxidative stress in streptozotocin-induced diabetic rats. , 2013, Molecular nutrition & food research.

[26]  V. Nejati,et al.  Sesame effects on testicular damage in streptozotocin-induced diabetes rats , 2013, Avicenna journal of phytomedicine.

[27]  W. Owiredu,et al.  Association between metabolic syndrome and sexual dysfunction among men with clinically diagnosed diabetes , 2013, Diabetology & Metabolic Syndrome.

[28]  D. Šuput,et al.  Achieving the Balance between ROS and Antioxidants: When to Use the Synthetic Antioxidants , 2013, Oxidative medicine and cellular longevity.

[29]  J. Słowikowska-Hilczer,et al.  The role of oxidative stress and antioxidants in male fertility , 2013, Central European journal of urology.

[30]  S. Suresh,et al.  Effect of Mucuna pruriens (Linn.) on sexual behavior and sperm parameters in streptozotocin-induced diabetic male rat. , 2012, The journal of sexual medicine.

[31]  R. Chang,et al.  Polysaccharides from Wolfberry Prevents Corticosterone-Induced Inhibition of Sexual Behavior and Increases Neurogenesis , 2012, PloS one.

[32]  M. Kanter,et al.  Protective effects of quercetin against apoptosis and oxidative stress in streptozotocin-induced diabetic rat testis. , 2012, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[33]  L. Qian,et al.  Hydrogen-rich saline attenuates radiation-induced male germ cell loss in mice through reducing hydroxyl radicals. , 2012, The Biochemical journal.

[34]  M. Isidro,et al.  Sexual dysfunction in men with type 2 diabetes , 2012, Postgraduate medical journal.

[35]  J. Anselmo-Franci,et al.  Vitamin C partially attenuates male reproductive deficits in hyperglycemic rats , 2011, Reproductive biology and endocrinology : RB&E.

[36]  M. Kupka,et al.  Correction: Evidence of inhibin/activin subunit betaC and betaE synthesis in normal human endometrial tissue , 2011, Reproductive Biology and Endocrinology : RB&E.

[37]  M. Shalaby,et al.  Safety and efficacy of Zingiber officinale roots on fertility of male diabetic rats. , 2010, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[38]  M. Nouri,et al.  Beneficial effects of quercetin on sperm parameters in streptozotocin‐induced diabetic male rats , 2010, Phytotherapy research : PTR.

[39]  M. Zirie,et al.  Is male fertility associated with type 2 diabetes mellitus? , 2009, International Urology and Nephrology.

[40]  E. Martino,et al.  Alterations in sperm motility after acute oral administration of sildenafil or tadalafil in young, infertile men. , 2007, Fertility and sterility.

[41]  Neil McClure,et al.  Sildenafil citrate improves sperm motility but causes a premature acrosome reaction in vitro. , 2007, Fertility and sterility.

[42]  G. Klinefelter,et al.  Sexual behaviour, sperm quantity and quality after short-term streptozotocin-induced hyperglycaemia in rats. , 2006, International journal of andrology.

[43]  Shenghua Zhang,et al.  Lycium barbarum polysaccharides: Protective effects against heat-induced damage of rat testes and H2O2-induced DNA damage in mouse testicular cells and beneficial effect on sexual behavior and reproductive function of hemicastrated rats. , 2006, Life sciences.

[44]  D. Franken,et al.  Effect of acute in vivo sildenafil citrate and in vitro 8-bromo-cGMP treatments on semen parameters and sperm function. , 2004, Fertility and sterility.

[45]  K. Bojanowski,et al.  Protective effect of Fructus Lycii polysaccharides against time and hyperthermia-induced damage in cultured seminiferous epithelium. , 2002, Journal of ethnopharmacology.

[46]  S. Srinivasula,et al.  Cytochrome c and dATP-Dependent Formation of Apaf-1/Caspase-9 Complex Initiates an Apoptotic Protease Cascade , 1997, Cell.