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Mitochondria-Mediated Apoptosis Induced Testicular Dysfunction in Diabetic Rats: Ameliorative Effect of Resveratrol
1Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
Abstract:
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.
Insights
Diabetes causes testicular damage through apoptosis and oxidative stress. Resveratrol treatment improved function by reducing these effects, offering a potential therapeutic strategy.
Area of Science:
- Reproductive Biology
- Endocrinology
- Mitochondrial Biology
Background:
- Diabetes mellitus is a complex metabolic disorder with significant systemic complications.
- Testicular dysfunction is a recognized complication of diabetes, impacting male reproductive health.
- The precise molecular mechanisms driving diabetes-induced testicular damage remain incompletely understood.
Purpose of the Study:
- To investigate the role of mitochondria-mediated apoptosis in diabetes-induced testicular dysfunction in rats.
- To explore the potential protective effects of resveratrol against diabetes-induced testicular damage.
Main Methods:
- Induction of diabetes in rats and subsequent assessment of testicular function, including sperm parameters and serum testosterone levels.
- Evaluation of mitochondrial function, including membrane potential and apoptosis markers (Bax, Bcl-2, Caspase-3, Caspase-9, Cytochrome C).
- Assessment of oxidative stress markers (antioxidant enzymes, H2O2, protein carbonyls, lipid peroxidation) and histological changes in testicular tissue.
- Administration of resveratrol to diabetic rats to evaluate its ameliorative effects.
Main Results:
- Diabetes significantly impaired sperm count, motility, viability, and increased abnormalities, while decreasing testosterone levels and mitochondrial membrane potential.
- Diabetes elevated pro-apoptotic markers (Bax, Caspase-3, Caspase-9) and the Bax/Bcl-2 ratio, with decreased anti-apoptotic Bcl-2, and altered Cytochrome C localization, indicating mitochondrial apoptosis.
- Diabetic rats exhibited suppressed antioxidant capacity, increased oxidative stress (H2O2, protein carbonyls, lipid peroxidation), and testicular tissue damage.
- Resveratrol treatment (50 mg/kg/day for 4 weeks) effectively ameliorated these diabetes-induced testicular dysfunctions and pathological alterations.
Conclusions:
- Diabetes induces testicular damage primarily through the induction of mitochondrial-mediated apoptosis and oxidative stress.
- Resveratrol demonstrates significant protective effects against diabetes-induced testicular damage, likely via its antioxidant and anti-apoptotic properties.
- These findings highlight a potential therapeutic role for resveratrol in managing male reproductive complications associated with diabetes.
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