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Title: Modulatory Effects of Resveratrol on c-Jun N-terminal Kinase Signaling and Apoptosis in Diabetic Rat Testis
Authors: Iman Mansour Faid 
Supervisor: Dr. Narayana Kilarkaje
Keywords: c-Jun N-terminal Kinase Apoptosis Diabetic Rat Testis
Issue Date: 2015
Publisher:  Kuwait university - college of graduate studies
Abstract: Diabetes mellitus (DM) adversely affects almost all organ systems including reproductive organs. The present study investigated the effects of an antioxidant Resveratrol on diabetes-induced alterations in oxidative stress, c-Jun N-terminal kinase (JNK) signaling pathway and cell death in rat testis. Adult male Wistar rats (13-15 weeks; n=5-6) were segregated into four groups: 1) normal control, 2) Resveratrol-treated, 3) Diabetes, and 4) Diabetes + Resveratrol-treated groups. The rats in group 3 were made diabetic by a single i.p. injection of 60 mg/kg body weight of Streptozotocin. The animals in groups 2 and 4 were administered 5 mg/kg body weight of Resveratrol during the last 3 weeks of the experiment. All animals were euthanized at the end of 6th week. Resveratrol recovered diabetes-induced decreases in reproductive organ weights, sperm count and motility, intra-testicular antioxidants (quantified by plate reader assays) such as superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx) and an increase in 4-hydroxynonenal (quantified by dot blotting) activities (P<0.05-0.001). The Resveratrol supplementation to diabetic rats also recovered the activities (quantified by Western blotting) of members of JNK signaling pathway 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 recovered diabetes-induced increase in the expression of AP-1 (activator protein-1) transcription factor components- c-Jun and ATF2 (activating transcription factor 2) to normal control levels (P<0.05). However, the phosphorylated forms of these two proteins (p-c-Jun and p-ATF2) did not show statistically significant differences between the groups. Resveratrol also recovered diabetes-induced increase in cleaved caspase-3 to normal control levels. Caspase-3 activity showed a trend to decrease in diabetic rats treated with Resveratrol but the difference with the diabetes group was not statistically significant. In conclusion, Resveratrol reduces diabetes-induced oxidative stress, normalizes JNK signaling pathway and alleviates the induced apoptosis in rat testis. Further, these results suggest that the supplementation of Resveratrol to diabetics may be a useful therapeutic strategy to alleviate diabetes-induced male reproductive dysfunction.
Appears in Programs:0560 Anatomy

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