stilbenes and Testicular-Diseases

The present study aimed to evaluate the protective role of resveratrol and curcumin on oxidative testicular damage induced by di-(2-ethylhexyl) phthalate (DEHP). Male Wistar rats were divided into six groups; three groups received oral daily doses of DEHP (2g/kgBW) for 45days to induce testicular injury. Two of these groups received either resveratrol (80mg/kgBW) or curcumin (200mg/kgBW) orally for 30days before and 45days after DEHP administration. A vehicle-treated control group was also included. Another two groups of rats received either resveratrol or curcumin alone. Oxidative damage was observed by decreased levels of total antioxidant capacity (TAC) and glutathione (GSH) and increased malondialdehyde (MDA) level in the testes of DEHP-administered rats. Serum testosterone level as well as testicular marker enzymes activities; acid and alkaline phosphatases (ACP and ALP) and lactate dehydrogenase (LDH) showed severe declines. DEHP administration caused significant increases in the testicular gene expression levels of Nrf2, HO-1, HSP60, HSP70 and HSP90 as well as a significant decrease in c-Kit protein when compared with the control group. Histopathological observations provided evidence for the biochemical and molecular analysis. These DEHP-induced pathological alterations were attenuated by pretreatment with resveratrol and curcumin. We conclude that DEHP-induced injuries in biochemical, molecular and histological structure of testis were recovered by pretreatment with resveratrol and curcumin. The chemoprotective effects of these compounds may be due to their intrinsic antioxidant properties along with boosting Nrf2, HSP 60, HSP 70 and HSP 90 gene expression levels and as such may be useful potential tools in combating DEHP-induced testicular dysfunction.

Topics: Alkaline Phosphatase; Animals; Antioxidants; Curcumin; Diethylhexyl Phthalate; Gene Expression; Glutathione; Heat-Shock Proteins; Heme Oxygenase-1; Male; Malondialdehyde; Protective Agents; Rats; Rats, Wistar; Resveratrol; Stilbenes; Testicular Diseases; Testis; Testosterone

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 (13-15 weeks; n=6/group) were segregated into 1) normal control, 2) Resveratrol-treated (5mg/kg; ip; given during last 3 weeks), 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 54 kDa 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.

Topics: Animals; Antioxidants; Apoptosis; Caspase 3; Diabetes Mellitus, Experimental; Glutathione Peroxidase; Hyperglycemia; JNK Mitogen-Activated Protein Kinases; Male; MAP Kinase Kinase 4; Oxidative Stress; Rats; Rats, Wistar; Resveratrol; Signal Transduction; Stilbenes; Streptozocin; Superoxide Dismutase; Testicular Diseases; Transcription Factor AP-1

To study the effect of resveratrol on spermatogenesis after 2,5-hexanedione(2,5-HD)-induced testicular injury.. Forty male SD rats were randomly divided into 5 groups. Group A were normally raised and Group B, C, D and E exposed to 1% 2,5-HD for 5 weeks, followed by administration of resveratrol of different concentrations (20, 40 and 80 mg/[ kg x d], respectively) to Group C, D and E for 9 weeks. Then the rats were killed, their physical signs, body weight gain and testis weight were assessed, and immunohistochemistry and Western blot analysis used to investigate the numbers and diameters of seminiferous tubules and the expression of c-kit protein of spermatogenic cell membrane.. The rats exposed to 2,5-HD showed weak body, lax skin, dim color pattern, tardy body weight gain, and emaciated testis. Immunohistochemistry revealed emaciated seminiferous tubules, stagnant obsolete spermatogonia and negative expression of c-kit protein. After resveratrol administration, the 2,5-HD-induced physical signs were improved and close to normal. Compared with those of the 2,5-HD injured group, the body weight and testis weight of the resveratrol treated group increased obviously (P < 0.01); and the aliquots of the seminiferous epithelia began to differentiate and the spermatogenesis and expression of c-kit protein partly resumed (P < 0.01). With increasing dose of resveratrol, the diameters and numbers of seminiferous tubules (P < 0.01) and the expression levels of c-kit protein (P < 0.01) were gradually and significantly restored almost to normal.. Resveratrol could promote the recovery of spermatogenesis after 2,5-HD-induced testicular injury.

Topics: Animals; Antineoplastic Agents, Phytogenic; Blotting, Western; Hexanones; Immunohistochemistry; Male; Proto-Oncogene Proteins c-kit; Rats; Rats, Sprague-Dawley; Resveratrol; Seminiferous Epithelium; Spermatogenesis; Stilbenes; Testicular Diseases; Testis