Diabetes-induced Testicular Dysfunction Research Articles

Ameliorating diabetes-induced testicular dysfunction by modulating PKC/Nrf2/Bcl-2 signaling: Protective role of sulbutiamine.

The prevalence of testicular dysfunction is increasing as it is a common diabetes mellites (DM) complication. The objective of this study is to explore the potential protective effect of sulbutiamine against testicular hypofunction associated with streptozotocin (STZ)-induced DM in rats. Sulbutiamine was administered orally (60 mg/kg) to male Wistar rats for 8 weeks starting 72 h after a single injection of STZ (45 mg/kg, i.p.). Blood glucose level (BGL), serum testosterone level, sperm number, and motility were determined. Testicular tissue was examined histopathologically, and the Johnson score was evaluated. Levels of malondialdehyde (MDA), protein kinase C (PKC), nuclear factor erythroid-derived 2-like 2 (Nrf2), and proliferating cell nuclear antigen (PCNA) were measured. Apoptosis was evaluated by immunohistochemical determination of B-cell lymphoma protein 2 (Bcl-2), Bcl-2 associated X-protein (Bax), and caspase-3. Sulbutiamine administration managed to reduce BGL and boost testicular function as manifested by increased testicular weight, testosterone level, sperm number, and motility compared to the STZ group. Additionally, histopathological examination revealed an improved histological picture and Johnson score of testicular tissue after sulbutiamine treatment. Sulbutiamine administration reduced testicular PKC, MDA, and PCNA levels and increased Nrf2 compared to the untreated group. Moreover, sulbutiamine treatment suppressed apoptosis triggered by STZ as evidenced by elevated Bcl-2, decreased Bax and reduced caspase-3. The present work revealed for the first time a promising protective role of sulbutiamine against STZ-induced testicular dysfunction which may add to the clinical utility of sulbutiamine. The underlying mechanisms involve reducing BGL and PKC, activating Nrf2 and inhibiting apoptosis.

Combination Therapy with Enalapril and Paricalcitol Ameliorates Streptozotocin Diabetes-Induced Testicular Dysfunction in Rats via Mitigation of Inflammation, Apoptosis, and Oxidative Stress.

As the impacts of diabetes-induced reproductive damage are now evident in young people, we are now in urgent need to devise new ways to protect and enhance the reproductive health of diabetic people. The present study aimed to evaluate the protective effects of enalapril (an ACE inhibitor) and paricalcitol (a vitamin D analog), individually or in combination, on streptozotocin (STZ)-diabetes-induced testicular dysfunction in rats and to identify the possible mechanisms for this protection. This study was carried out on 50 male Sprague-Dawley rats; 10 normal rats were allocated as a non-diabetic control group. A total of 40 rats developed diabetes after receiving a single dose of STZ; then, the diabetic rats were divided into four groups of equivalent numbers assigned as diabetic control, enalapril-treated, paricalcitol-treated, and combined enalapril-and-paricalcitol-treated groups. The effects of mono and combined therapy with paricalcitol and enalapril on testicular functions, sperm activity, glycemic state oxidative stress, and inflammatory parameters, as well as histopathological examinations, were assessed in comparison with the normal and diabetic control rats. As a result of diabetes induction, epididymal sperm count, sperm motility, serum levels of testosterone, follicle-stimulating hormone (FSH) as well as luteinizing hormone (LH), and the antioxidant enzyme activities, were significantly decreased, while abnormal sperm (%), insulin resistance, nitric oxide (NO), malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were significantly increased, along with severe distortion of the testicular structure. Interestingly, treatment with paricalcitol and enalapril, either alone or in combination, significantly improved the sperm parameters, increased antioxidant enzyme activities in addition to serum levels of testosterone, FSH, and LH, reduced insulin resistance, IL-6, and TNF-α levels, and finally ameliorated the diabetes-induced testicular oxidative stress and histopathological damage, with somewhat superior effect for paricalcitol monotherapy and combined therapy with both drugs compared to monotherapy with enalapril alone. Monotherapy with paricalcitol and its combination therapy with enalapril has a somewhat superior effect in improving diabetes-induced testicular dysfunction (most probably as a result of their hypoglycemic, antioxidant, anti-inflammatory, and anti-apoptotic properties) compared with monotherapy with enalapril alone in male rats, recommending a synergistic impact of both drugs.

The protective effects and underlying mechanisms of dapagliflozin on diabetes-induced testicular dysfunction.

Male diabetic individuals present a marked impairment in fertility; however, knowledge regarding the pathogenic mechanisms and therapeutic strategies is unsatisfactory. The new hypoglycemic drug dapagliflozin has shown certain benefits, such as decreasing the risk of cardiovascular and renal events in patients with diabetes. Even so, until now, the effects and underlying mechanisms of dapagliflozin on diabetic male infertility have awaited clarification. Here, we found that dapagliflozin lowered blood glucose levels, alleviated seminiferous tubule destruction, and increased sperm concentrations and motility in leptin receptor-deficient diabetic db/db mice. Moreover, the glucagon-like peptide-1 receptor (GLP-1R) antagonist exendin (9-39) had no effect on glucose levels but reversed the protective effects of dapagliflozin on testicular structure and sperm quality in db/db mice. We also found that dapagliflozin inhibited the testicular apoptotic process by upregulating the expression of the antiapoptotic protein B-cell lymphoma 2 (BCL2) and X-linked inhibitor of apoptosis protein (XIAP) and inhibiting oxidative stress by enhancing the antioxidant status, including total antioxidant capacity, total superoxide dismutase (SOD) activity, and glutathione peroxidase (GPx) activity, as well as decreasing the level of 4-hydroxynonenal (4-HNE). Exendin (9-39) administration partially reversed these effects. Furthermore, dapagliflozin upregulated the glucagon-like peptide-1 (GLP-1) level in plasma and GLP-1R expression by promoting AKT8 virus oncogene cellular homolog (Akt) phosphorylation in testicular tissue. Exendin (9-39) partially inhibited Akt phosphorylation. These results suggest that dapagliflozin protects against diabetes-induced spermatogenic dysfunction via activation of the GLP-1R/phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Our results indicate the potential effects of dapagliflozin against diabetes-induced spermatogenic dysfunction.

Role of PPAR-γ in diabetes-induced testicular dysfunction, oxidative DNA damage and repair in leptin receptor-deficient obese type 2 diabetic mice

The testis expresses peroxisome proliferator-activated receptor-γ (PPAR-γ), but its involvement in regulating diabetes-induced testicular dysfunction and DNA damage repair is not known. Pioglitazone-induced activation of PPAR-γ for 12 weeks in db/db obese diabetic mice increases bodyweights and reduces blood glucose levels, but PPAR-γ inhibition by 2-chloro-5-nitro-N-phenylbenzamide does not alter these parameters; instead, improves testis and epididymis weights and sperm count. Neither activation nor inhibition of PPAR-γ normalizes the diabetes-induced seminiferous epithelial degeneration. The PPAR-γ activation normalizes testicular lipid peroxidation, but its inhibition reduces lipid peroxidation and oxidative DNA damage (8-oxo-dG) in diabetic mice. As a response to diabetes-induced oxidative DNA damage, the base-excision repair (BER) mechanism proteins- 8-oxoguanine DNA glycosylases (OGG1/2) and X-ray repair cross-complementing protein-1 (XRCC1) increase, whereas the redox-factor-1 (REF1), DNA polymerase (pol) δ and poly (ADP-ribose) polymerase-1 (PARP1) show a tendency to increase suggesting an attempt to repair the oxidative DNA damage. The PPAR-γ stimulation inhibits OGG2, DNA pol δ, and XRCC1 in diabetic mice testes, but PPAR-γ inhibition reduces oxidative DNA damage and normalizes BER protein levels. In conclusion, type 2 diabetes negatively affects testicular structure and function and increases oxidative DNA damage and BER protein levels due to increased DNA damage. The PPAR-γ modulation does not significantly affect the structural changes in the testis. The PPAR-γ stimulation aggravates diabetes-induced effects on testis, including oxidative DNA damage and BER proteins, but PPAR-γ inhibition marginally recovers these diabetic effects indicating the involvement of the receptor in the reproductive effects of diabetes.

Mitochondria-Mediated Apoptosis Induced Testicular Dysfunction in Diabetic Rats: Ameliorative Effect of Resveratrol.

The molecular mechanism underlying diabetes-induced testicular damage has not been thoroughly elucidated. The present study was conducted to elucidate the role of mitochondria-mediated apoptosis in diabetes-induced testicular dysfunction in rats and to explore the ameliorative effect of resveratrol. Diabetes suppressed sperm count, motility, and viability and increased sperm abnormalities. It decreased serum testosterone level and testicular mitochondrial membrane potential. The level of Bax and caspase-3 and -9 activities were increased in the testicular cytosol, while the level of Bcl-2 was decreased. Diabetes increased the Bax/Bcl-2 ratio. The cytochrome C level was decreased in the mitochondrial fraction, while its level was increased in the cytosol, a result that was supported by the immunohistochemistry of cytochrome C. Diabetes resulted in deleterious alterations in the architecture of testicular tissue, suppressed antioxidant enzymes, and increased H2O2 production, protein carbonyl content, and lipid peroxidation. However, administration of resveratrol at a dose of 50 mg kg/day for 4 successive weeks post diabetic induction, successfully ameliorated the testicular dysfunction. In conclusion, these findings strongly reveal that diabetes induces testicular damage, at least in part, by inducing mitochondrial-mediated apoptosis and oxidative stress. Administration of resveratrol to diabetic rats improves the diabetes-induced testicular damage. These impacts could be mediated through resveratrol antioxidant and anti-apoptotic effects.

Clusterin suppresses spermatogenic cell apoptosis to alleviate diabetes-induced testicular damage by inhibiting autophagy via the PI3K/AKT/mTOR axis.

Diabetes-induced testicular dysfunction is characterised by abnormal apoptosis of spermatogenic cells, but the underlying mechanism is poorly understood. This study aimed to investigate the roles of clusterin (CLU) in testicular damage associated with diabetes pathogenesis, as well as the molecular mechanism. A rat diabetes model was established using streptozocin, and the mouse spermatogenic cell line GC-1 spg was treated with high glucose as a cellular model. CLU was overexpressed in GC-1 spg cells, followed by detection of serum testosterone, cell proliferation, cell apoptosis and autophagy. CLU expression was significantly reduced and LC3 expression was elevated in testis tissues in the rat diabetes model and high glucose-treated GC-1 spg cells. High glucose led to suppressed viability, enhanced apoptosis, reduced Bcl-2 expression, elevated Bax expression and cleavage of Caspase-3/-9 in GC-1 spg cells, and these effects were abrogated by CLU overexpression. Additionally, CLU overexpression repressed LC3 and Beclin-1 expression, reduced the LC3II/LC3I ratio and promoted p62 expression in GC-1 spg cells in the presence of high glucose, and these effects were all mitigated by rapamycin treatment. Inhibition of PI3K/AKT/mTOR signalling with LY294002 activated autophagy in CLU-overexpressing GC-1 spg cells under high glucose conditions. CLU overexpression repressed autophagy and alleviated testicular damage in diabetic rats, which was also abrogated by LY294002 treatment. CLU expression is suppressed during diabetes-induced testicular damage, whereas CLU overexpression alleviates diabetes-induced testicular damage by activating PI3K/AKT/mTOR signalling to inhibit autophagy and further repress spermatogenic cell apoptosis.

Nanoparticles of Antroquinonol-Rich Extract from Solid-State-Cultured Antrodia cinnamomea Improve Reproductive Function in Diabetic Male Rats.

PurposeTo characterize the nanoparticle of antroquinonol from A. cinnamomea and its ameliorative effects on the reproductive dysfunction in the diabetic male rat.Material and MethodsThe chitosan-silicate nanoparticle was used as the carrier for the delivery of antroquinonol from solid-state-cultured A. cinnamomea extract (AC). The rats were fed with a high-fat diet and intraperitoneally injected with streptozotocin to induce diabetes. The rats were daily oral gavage by water [Diabetes (DM) and Control groups], three different doses of chitosan-silicate nanoparticle of antroquinonol from solid-state-cultured A. cinnamomea (nano-SAC, NAC): (DM+NAC1x, 4 mg/kg of body weight; DM+NAC2x, 8 mg/kg; and DM+NAC5x, 20 mg/kg), solid-state-cultured AC (DM+AC5x, 20 mg/kg), or metformin (DM+Met, 200 mg/kg) for 7 weeks.ResultsThe nano-SAC size was 37.68±5.91 nm, the zeta potential was 4.13±0.49 mV, encapsulation efficiency was 79.29±0.77%, and loading capacity was 32.45±0.02%. The nano-SAC can improve diabetes-induced reproductive dysfunction by regulating glucose, insulin, and oxidative enzyme and by increasing the level of testosterone, follicle-stimulating hormone, luteinizing hormone, and sperm count as well as sperm mobility. In testicular histopathology, the seminiferous tubules of A. cinnamomea-supplemented diabetic rats showed similar morphology with the control group.ConclusionThe nanoparticle of antroquinonol from Antrodia cinnamomea can be used as an effective strategy to improve diabetes-induced testicular dysfunction.

Auricularia Polytricha (Mushroom) Regulates Testicular DNA Expression and Oxidative Stress Markers of Streptozotocin-Induced Diabetic Male Wistar Rat

Local Nigerian men have been using AuriculariaPolytricha as a treatment for sexual dysfunction without supporting evidence from scientific experiments. This study was to investigate the effect of ethanolic extract of A. Polytricha on testicular DNA expression and some oxidative stress markers using STZ-Induced diabetic rats as a model. The experiment included six groups, Group A (Normal Control, treated with normal saline), Group B (treated with 65mg/kg.bw of STZ), Groups C, D, and E (treated with 250mg/kg.bw, 500mg/kg.bw, 1000mg/kg.bw AP after inducing diabetics), and Group F (treated with 40mg/kg.bw metformin after inducing diabetics). The experiment lasted for 35 days. After termination of the experiment, Fuelgen nuclear reaction was used for DNA demonstration to assess testicular DNA distribution while serum Superoxide Dimutase (SOD), Catalase and Melondialdehyde where evaluated using reagent based antioxidant enzyme assay. Results reveals that SOD and Melondialdehyde activities were remarkably (p<0.05) higher in diabetic control animals when compared with the normal control group. Values in Groups C, D and F that were administered with 250, 500mg/kg.bw A. polytricha and metformin respectively were also significantly (p<0.05) increased when compared with the normal control group. However, diabetic animals placed on 1000mg/kg.bw A. polytrichadid not show any statistical significance in comparison with normal control group but was remarkably (p<0.01) decreased when compared to the diabetic group that received low dose A. polytricha, an indication that the reversal is dose dependent. Catalase concentration in diabetic control animals was remarkably (p<0.05) higher when compared to the normal control but was not significantly (p<0.05) different in groups D (DM+500mg/kg.bw A. polytricha) and E (DM+1000mg/kg.bw A. polytricha) when compared with the normal control group. Diabetic control animals showed reduced magenta colour intensity of DNA and increased clustering and cross linking of DNA strands when compared with the normal control. However the degree of cross link in DNA strands was reduced in the diabetic animals placed on 1000mg/kg.bw A. polytrichawhen compared with the diabetic control group. Reversal in DNA damage and values of serum oxidative stress markers following administration of graded doses of A. polytricha could be attributed to essential phytochemical and therapeutic constituents in A. polytricha like polyphenol and flavonoid which can be found useful in prevention and treatment of diabetes induced testicular dysfunction. In summary, AP can contribute to a reversal in DNA damage and levels of serum oxidative stress markers in treating diabetes-induced testicular dysfunction.

Correction of diabetes-induced testicular dysfunction by a hydro-methanol (60:40) extract of Curcuma amada rhizomes: A dose-dependent study.

Diabetes affects the reproductive system. This study was conducted to find out the potent dose of the hydro-methanol 60:40 extract of Curcuma amada rhizomes for the management of diabetes-induced testicular dysfunction in albino rats. The extract was administered at the doses of 10, 20, 40, and 80mg/100g body weight/day for 28days. Oxidative stresses, reproductive parameters, histological, and gene expressions of the testicular tissue were assessed. Out of the doses used, the 20-mg dose showed maximum recovery as the minimum dose (e.g., sperm motility 112.03%, testicular cholesterol 34.86%, Bax gene expression 49.77%), whereas 40- and 80-mg doses did not vary statistically with each other (e.g., sperm motility 95.37% and 89.19%, testicular cholesterol 30.42% and 28.41%, Bax gene expression 47.33% and 46.18%, respectively) as well as with the 20-mg dose. It may be concluded that the 20-mg dose is the threshold dose for this purpose. PRACTICAL APPLICATIONS: The hydro-methanol 60:40 extract of rhizomes of Curcuma amada has a strong antioxidant property that can manage diabetes-induced oxidative injuries in testes which may raise a hope to the pharmaceutical industries to develop a herbal drug for diabetes-linked testicular hypofunction management.

Taurine and pioglitazone attenuate diabetes-induced testicular damage by abrogation of oxidative stress and up-regulation of the pituitary-gonadal axis.

Chronic hyperglycemia is associated with impairment of testicular function. The current study aimed to investigate the protective effects and the possible mechanisms of taurine and pioglitazone against diabetes-induced testicular dysfunction in rats. Diabetes was induced by streptozotocin injection. Both normal and diabetic rats received taurine (100 mg/kg) or pioglitazone (10 mg/kg) orally and daily for 6 weeks. Diabetic rats showed a significant (P < 0.001) increase in glycosylated hemoglobin, glucose, homeostasis model of insulin resistance, and pro-inflammatory cytokines. Serum insulin, testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were significantly (P < 0.001) decreased in diabetic rats. Taurine and pioglitazone alleviated hyperglycemia, decreased pro-inflammatory cytokines, and increased circulating levels of insulin, testosterone, LH, and FSH. Gene and protein expression of LH and FSH receptors and cytochrome P450 17α-hydroxylase (CYP17) was significantly (P < 0.001) down-regulated in testes of diabetic rats, an effect which was significantly increased after administration of taurine and pioglitazone. In addition, taurine and pioglitazone significantly decreased lipid peroxidation and DNA damage, and enhanced activity of the antioxidant enzymes in testes of diabetic rats. In conclusion, taurine and pioglitazone exerted protective effects against diabetes-induced testicular damage through attenuation of hyperglycemia, inflammation, oxidative stress and DNA damage, and up-regulation of the pituitary/gonadal axis.

Resveratrol alleviates diabetes-induced testicular dysfunction by inhibiting oxidative stress and c-Jun N-terminal kinase signaling in rats

Diabetes adversely affects reproductive functions in humans and animals. The present study investigated the effects of Resveratrol on diabetes-induced alterations in oxidative stress, c-Jun N-terminal kinase (JNK) signaling and apoptosis in the testis. Adult male Wistar rats (13–15weeks; n=6/group) were segregated into 1) normal control, 2) Resveratrol-treated (5mg/kg; ip; given during last 3weeks), 3) Streptozotocin-induced diabetic and, 4) Resveratrol-treated diabetic groups, and euthanized on day 42 after the confirmation of diabetes. Resveratrol did not normalize blood glucose levels in diabetic rats. Resveratrol supplementation recovered diabetes-induced decreases in reproductive organ weights, sperm count and motility, intra-testicular levels of superoxide dismutase, catalase, and glutathione peroxidase and an increase in 4-hydroxynonenal activities (P<0.05). Resveratrol also recovered diabetes-induced increases in JNK signaling pathway proteins, namely, ASK1 (apoptosis signal-regulating kinase 1), JNKs (46 and 54kDa isoforms) and p-JNK to normal control levels (P<0.05). Interestingly, the expression of a down-stream target of ASK1, MKK4 (mitogen-activated protein kinase kinase 4) and its phosphorylated form (p-MKK4) did not change in experimental groups. Resveratrol inhibited diabetes-induced increases in AP-1 (activator protein-1) components, c-Jun and ATF2 (activating transcription factor 2), but not their phosphorylated forms, to normal control levels (P<0.05). Further, Resveratrol inhibited diabetes-induced increase in cleaved-caspase-3 to normal control levels. In conclusion, Resveratrol alleviates diabetes-induced apoptosis in testis by modulating oxidative stress, JNK signaling pathway and caspase-3 activities, but not by inhibiting hyperglycemia, in rats. These results suggest that Resveratrol supplementation may be a useful strategy to treat diabetes-induced testicular dysfunction.

Diabetes-induced DNA damage and apoptosis are associated with poly (ADP ribose) polymerase 1 inhibition in the rat testis

Molecular mechanisms responsible for diabetes-induced testicular dysfunction are not well understood. This study investigated oxidative stress, stage-dependent DNA base modification and expression of poly (ADP ribose) polymerase 1 (PARP1) in the testes of streptozotocin-induced diabetic rats. Hyperglycemia led to testicular dysfunction characterized by impaired sperm parameters and testicular structure at the end of first (DM1) and third (DM3) month after the induction of diabetes. In the testis, total oxidant levels increased and total antioxidant levels decreased, which led to the induction of oxidative stress status. The oxidative stress up-regulated the levels of 8-oxo-7, 8-dihydro-2′-deoxyguanosine – an oxidized form of the DNA base, deoxyguanosine – in a stage-dependent manner. In DM1, stage VII–IX tubules showed more cytoplasmic expression of 8-oxo-7, 8-dihydro-2′-deoxyguanosine in all germ cell types and the Sertoli cells than did the other stage tubules, which suggested mitochondrial DNA damage. In DM3, mainly a stage-dependent nuclear expression of 8-oxo-7, 8-dihydro-2′-deoxyguanosine was observed in germ cells, but not in the Sertoli cells. Diabetes increased the cytoplasmic expression of 4-hydroxynonenal and concurrently inhibited the expression of both full length and 89kDa large cleaved-fragment of PARP1 in DM1 and DM3. The germ and Sertoli cells showed the nuclear expression of the protein in a stage-dependent manner, which decreased from DM1 to DM3. The increase in oxidative DNA damage and a decrease in PARP1 led to a stage-dependent induction of apoptosis of testicular cells. In conclusion, diabetes-induced oxidative stress, oxidative DNA damage and apoptosis occur in parallel with PARP1 inhibition in the testis.

Dracaena arborea alleviates ultra-structural spermatogenic alterations in streptozotocin-induced diabetic rats

BackgroundInfertility is a common complication in diabetic men and experimental animals, mainly due to loss of germ cells by apoptotic cell death. The aim of this study was to evaluate the effects of aqueous and ethanol extracts of Dracaena arborea in streptozotocin-induced ultra-structural spermatogenic alterations in Wistar rats.MethodsDiabetic animals were orally treated with Millipore water (10 ml/kg), sildenafil citrate (1.44 mg/kg) or Dracaena arborea aqueous (500 mg/kg) and ethanol (100 mg/kg) extracts for three weeks. A group of non diabetic rats received Millipore water (10 ml/kg) and served as healthy control group. Blood glucose was monitored at the beginning and the end of the study. One day after the last treatment, animals were sacrificed and the testes immediately removed were morphologically observed and prepared for electron microscopy analysis of spermatogenesis.ResultsOur results showed that Dracaena arborea was devoid of any anti-hyperglycemic activity. In the untreated diabetic rats, hyperglycemia severely damaged the testes morphology as well as the spermatogenic process as evidenced by the: thickness of basement membrane of the seminiferous tubule; mitochondria alteration; abnormal spermatocyte cells displaying polymorphous nuclei, cytoplasmic vacuolization and necrosis; and disorganization and degeneration of sperm germ cells. Administration of sildenafil citrate and Dracaena arborea extracts to the diabetic rats improved testes morphology and reversed, although not completely, the impairment of spermatogenesis; this alleviating effect was more pronounced in animals treated with the aqueous extract (500 mg/kg) of Dracaena arborea.ConclusionDracaena arborea improves testes morphology and restores spermatogenesis in type 1 diabetic rats, without having major anti-hyperglycemic properties. These effects could be attributed to saponins, flavonoids, phenols and sterols revealed in this plant, which could be a useful component in the treatment of diabetes-induced testicular dysfunction.

Antioxidant treatment with edaravone or taurine ameliorates diabetes-induced testicular dysfunction in the rat

Diabetes mellitus with the subsequent generation of reactive oxygen species represents a major risk factor for testicular dysfunction (TD). We investigate whether administration of antioxidants edaravone and taurine could prevent type 1 diabetes-induced TD in the rat. Six-week-old male Wistar rats were divided into four groups. Group A was treated with citrate-phosphate buffer plus normal saline, whereas in the other three groups, diabetes was induced by streptozotocin (50 mg/kg intraperitoneally). Subsequently, the diabetic rats were treated for 4 weeks either with normal saline (group B), edaravone (10 mg/Kg/day, intraperitoneally; group C), or taurine (500 mg/Kg/day, intraperitoneally; group D). Body, testicular, and epididymal weight, serum glucose, malondialdehyde levels, 8-Hydroxy-2'-deoxyguanosine(8-OH-dG) levels, testicular catalase activity, and serum testosterone levels were determined. Histological examination and the Johnsen score were used to observe and evaluate, respectively, the morphological changes in the testes. TUNEL assay was used to examine DNA fragmentation. Mating studies were performed in order to evaluate the fertility potential of male rats in each group. Edaravone or taurine treatment prevented significantly the decreased body, testicular, and epididymal weight induced by diabetes. Moreover, edaravone or taurine significantly decreased the diabetes-induced malondialdehyde levels, 8-OHdG levels, the morphological damage, and the number of apoptotic cells. Taurine, but not edaravone, increased significantly the testicular catalase activity. The antioxidant treatment had no effect on the fertility potential of the diabetic rats. The morphological damage, increased lipid peroxidation, and apoptosis in testicular tissue can be significantly relieved by edaravone or taurine treatment through suppressing the increased oxidative stress in the rat testis.

The Antiapoptotic Effects of Sulphurous Mineral Water and Sodium Hydrosulphide on Diabetic Rat Testes

Background/Aims: It is well known that diabetes mellitus is associated with the impairment of testicular function. In the present study, we aimed to study the effects of sulphurous mineral water or sodium hydrosulphide (NaHS) on apoptotic testicular damage in rats with streptozotocin (STZ)-induced diabetes. Methods: Sulphurous mineral water (as drinking water) or NaHS (14 µmol/kg body weight/day, I.P.) was administered for 7 wks to rats with STZ-induced diabetes. Results: Hyperglycaemia, an overproduction of glycated haemoglobin (HbA1C) and a decline in serum insulin, C-peptide and insulin-like growth factor-I (IGF-I) were observed in diabetic rats. A decline in the serum testosterone level and an impairment of spermatogenesis, as indicated by a histopathological examination of diabetic rats, demonstrated significant testicular damage. Sulphurous mineral water and NaHS treatment may have improved the level of testicular GSH by blocking the overexpression of some apoptosis-related regulatory proteins such as Bax/Bcl-2, cytochrome c, caspase-9 and -3, and p53. This anti-apoptotic potential was associated with an increase in serum testosterone level and the amelioration of hyperglycaemia-related biochemical parameters. The histopathological examination was in harmony with the biochemical and molecular findings. Conclusion: Our study provides the first indication that sulphurous mineral water and NaHS may have a novel anti-apoptotic potential that could be a useful treatment in preventing diabetes-induced testicular dysfunction.