Curcumin nano-micelle induced testicular toxicity in healthy rats; evidence for oxidative stress and failed homeostatic response by heat shock proteins 70-2a and 90

This study explores the effect of curcumin nano-micelle (NCMN) on the testicular anti-oxidant status and heat shock proteins (Hsp) 70–2a and Hsp 90 expression. Therefore, 24 male Wistar rats were divided into control, 7.50 mg/kg, 15 mg/kg, and 30 mg/kg of NCMN-received groups. Following 48 days, the testicular total anti-oxidant capacity (TAC), total oxidant status (TOS), malondialdehyde (MDA) and glutathione (GSH), catalase (CAT) and glutathione peroxidase (GPX) activities, immunoreactivity of 8-oxodG, Hsp70–2a and Hsp90 expressions, germ cell’s DNA and mRNA damages, the spermatozoa count, motility and DNA integrity were assessed. With no change in the testicular TAC level, the TOS, MDA and GSH contents were increased in the NMC-received groups. However, CAT and GPX activities were decreased. The NCMN suppressed spermatogenesis, increased immunoreactivity of 8-oxodG, stimulated the Hsp70–2a and Hsp90 expressions, and resulted in severe DNA and mRNA damages. Moreover, the NCMN-received animals exhibited remarkable reductions in the spermatozoa count, motility and DNA integrity. In conclusion, chronic and high dose consumption of NCMN initiates OS, and in response to OS, the Hsp70–2a and Hsp90 expression increases. However, considering enhanced DNA and mRNA damages and suppressed spermatogenesis, HSPs over-expression can neither boost the anti-oxidant system nor overcome the NCMN-induced OS-related damages. Summarized crosstalk between HSP 70–2a, HSP 90 and antioxidant defense system in A) Physiological condition and mild stress condition and B) Under nano-micelle-curcumin (NCMN)-induced oxidative stress condition. In the physiological condition, O2.- is converted to H2O2- by catalase and then the glutathione peroxidase (GPX) utilizes the reduced glutathione to detoxify H2O2- to H2O, resulting in a significant reduction in total oxidant status. Accordingly, a balance between antioxidant capacity and oxidant status maintains the cellular DNA, mRNA and lipid contents. Moreover, in mild stress conditions, the increased expressions of HSP 70–2a (at a higher level) and HSP 90 (at a lower level) stimulate the GPX expression/activity and in line up-regulate the enzymatic antioxidant capacity to overcome the stress. However, in more stressful conditions, with an unknown threshold of effect, the situation changes. With respect to our findings, NCMN significantly suppresses the GPX and catalase-dependent antioxidant capacity, resulting in high GSH stability, and in l