Lycopene attenuates d-galactose-induced insulin signaling impairment by enhancing mitochondrial function and suppressing the oxidative stress/inflammatory response in mouse kidneys and livers

Lycopene (LYC) possesses bioactivity to improve the pathogenesis of several chronic diseases via antioxidant-associated mechanisms. The purpose of this study was to investigate whether LYC could attenuate d-galactose (d-gal)-induced mitochondrial dysfunction and insulin signaling impairment in mouse kidneys and livers. Two-month-old CD-1 mice were treated by intraperitoneal injection of 150 mg kg(-1) day(-1)d-gal for 8 weeks and received 0.03% LYC (w/w, mixed into diet). The results showed that LYC ameliorated oxidative stress triggered by d-gal by enhancing the Nrf2 antioxidant defense pathway and increasing the expression of the antioxidant response genes HO-1 and NQO1 in mouse kidneys and livers. LYC inhibited the MAPK and NF kappa B pathways and attenuated renal and hepatic inflammatory responses. Moreover, LYC upregulated the expression of genes related to mitochondrial biosynthesis and oxidative phosphorylation and improved insulin signal transduction through the IRS-1/AKT/GSK3 beta pathway in mouse kidneys and livers.