Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
Volume 1852, Issue 1, Pages 70-82Publisher
ELSEVIER
DOI: 10.1016/j.bbadis.2014.11.007
Keywords
Oxidative and ER stress; Diabetes; Testicular damage; Endoplasmic reticulum and mitochondrial-dependent apoptosis; Antioxidant; Curcumin
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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 NF kappa B 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. (C) 2014 Elsevier B.V. All rights reserved.
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