Nanomicelle curcumin-induced testicular toxicity: Implications for altered mitochondrial biogenesis and mitophagy following redox imbalance

Abstract

The purpose of this study was to examine the effects of nano-micelle curcumin (NMC)-induced redox imbalance on mitochondrial biogenesis and mitophagy. For this purpose, 24 mature male Wistar rats were divided into control and NMC-received groups (7.5, 15, and 30 mg/kg) groups. After 48 days, the Nrf1, Nrf2, and SOD (Cu/Zn) expression levels, as well as GSH/GSSG, NADP+ /NADPH relative balances (elements involved in redox homeostasis) were analyzed. Moreover, to explore the effect of NMC on mitochondrial biogenesis, the expression levels of Mfn1, Mfn2, OPA1, Fis1, and Drp1 were investigated. Finally, the expression levels of Parkin/PARK and PINK (genes involved in mitochondrial quality control), as well as LC3-I/II (mitophagy marker), were analyzed. Observations showed that NMC, dose-dependently, altered GSH/GSSG, NADP+ /NADPH relative balances, suppressed SOD expression and diminished its biochemical level, and repressed Nrf1 and Nrf2 expression levels. Moreover, it could change the Mfn1, Mfn2, OPA1, Fis1, and Drp1 expression pattern and stimulate the Parkin/PARK and PINK as well as LC3-I/II expression levels, dose-dependently. In conclusion, chronic and high-dose NMC is able to suppress the redox capacity by down-regulating the Nrf1 and Nrf2 expression. Finally, at high-dose levels, it is able to trigger mitophagy signaling in the testicles.

Keywords: Biogenesis; Mitochondria; Mitophagy; Nano-micelle curcumin; Oxidative stress.