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

Abstract

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 (50mg/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 100mg/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 Ca(2+) 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.

Atorvastatin induced hepatic oxidative stress and apoptotic damage via MAPKs, mitochondria, calpain and caspase12 dependent pathways

“…Calpain may be responsible for cleaving procaspase-12, a caspase localized in ER to generate active caspase-12. Furthermore, caspase-12-deficient cells are resistant to inducers of ER stress, suggesting that caspase-12 is responsible in ER stress-induced apoptosis (Nakagawa and Yuan, 2000;Nakagawa et al, 2000;Rashid and Sil, 2015a;Rashid and Sil, 2015b). Caspase-12 translocates from ER to cytosol and then directly cleaves pro-caspase-9, which, in turn, activates caspase 3 that leads to cell death (Morishima et al, 2002).…”

Protective effects of the antioxidants curcumin, ellagic acid and methionine on motility, mitochondrial transmembrane potential, plasma membrane and acrosome integrity in freeze-thawed Merino ram sperm

“…Curcumin is a natural antioxidant, and has efficiency as an anti-apoptotic, cryoprotective, anti-oxidative, anti-inflammatory, anti-toxic and anti-cancer agent (Surh et al 2001;Mathuria and Verma 2008;Glombik et al 2014;Rashid and Sil 2015). Further, many studies in the literature have doi: 10.17221/8677-VETMED concluded that curcumin has potential in the prevention and treatment of a variety of diseases.…”

Therapeutic Insights against Oxidative Stress Induced Diabetic Nephropathy: A Review

“…It has been experimentally shown in different diabetic models that the level of different antioxidants got decreased, both transcriptionally and post-transcriptionally, in kidney tissue [88,89]. It is also shown that prevention of the overproduction of ROS by the administration of exogenous antioxidants is an effective strategy in combating DN [35,90,91]. Numerous studies suggest that antioxidants improve the renal physiology in DN by acting directly against oxidative damage.…”

“…Curcumin has caught scientific attention as a potential treatment for DN as it is a commonly consumed natural foodstuff and considered safe compared to the available expensive commercial drugs. Its diverse properties of regulating different signaling pathways, intracellular components and key enzymes are due to its inbuilt antidiabetic, antioxidant and antiinflammatory properties [90,122,123]. Its antioxidant property generally comes up due to its hydroxyl group or the methylene group of the α-diketone (heptadiene-dione) moiety [123].…”