Curcumin ameliorates testicular damage in diabetic rats by suppressing cellular stress-mediated mitochondria and endoplasmic reticulum-dependent apoptotic death

• STZ-induced oxidative and ER stress caused testicular dysfunction in diabetic rats.
• Curcumin protects testes from cellular stress by reducing hyperglycemia.
• Curcumin restores testicular dysfunction related markers like SDH and testosterone.
• Curcumin activates cellular defense protein Nrf-2 to protect testicular cells.
• Curcumin attenuates stress-mediated apoptotic pathways in testes.

In the present study, we sought to explore whether curcumin plays any beneficial role against STZ induced testicular abnormalities in diabetic rats, and if so, what possible mechanism it utilizes to provide protection. Exposure to STZ (50 mg/kg body weight, i.p., once) reduced testis-to-body weight ratio, enhanced blood glucose level and intracellular ROS, altered testicular markers, diminished serum testosterone and impaired cellular redox balance. Administration of curcumin at a dose of 100 mg/kg body weight for 8 weeks effectively normalized all the alterations. Curcumin also showed inhibitory effect on the elevation of pro-inflammatory cytokines and translocation of NFκB into the nucleus and promoted the activation of the transcription factor Nrf-2 to provide protection against oxidants. To protect cells from STZ-induced stress-mediated damage, curcumin acted on the key mediators of the apoptotic cell death such as JNK and p38. In addition, this active molecule upregulated Bcl-2 expression, blocked the expression of pro-apoptotic proteins (Bax, Bad and Bid), decreased intracellular Ca2 + level, inhibited active caspase cascade and attenuated PARP cleavage. These results suggest that curcumin provides protection against cellular stress-mediated mitochondrial and endoplasmic reticulum-dependent apoptotic death of the testicular cells under diabetic condition and suggests the possibility of using this molecule as a potential therapeutic in the treatment of stress-mediated diabetic testicular dysfunction.

Figure optionsDownload high-quality image (70 K)Download as PowerPoint slide