Lycopene Protects Against Atrazine-induced Nephrotoxicity Via Modulating Nrf2 Signaling Pathway

Atrazine(ATR) is one of the most extensively used herbicide. ATR is frequently detected in soil and surfacewater as a result of it’s persistence. Accumulation of ATR in food chains do harm to the health of human and animals. Lycopene(LYC) is one of the most powerful antioxidants which are found in natural plants, exerting defencive function to a variety of cells. Kidney is one of the main target organ of ATR-induced toxicity, however, the antagonistic effect of LYC on the renal toxicity remains unclear. In order to reveal the mechanism of LYC againsting ATR-induced nephrotoxicity, we have experimented on male Kun-Ming mice which were treat with ATR and/or LYC by intragastric administration. Renal pathological alteration was observed and Related indicators such as renal function, ATR and its main metabolites(DACT) contents, expression of renal nuclear receptor and CYP450 s, oxidative stress, Nrf2 signaling pathway and autophagy related genes were detected. The results indicated that:(1)LYC can depress ATR-induced alterations in renal function, decreasing ATR and DACT content in renal tissue, easing the histopathological and ultrastructural damage, showing antagonistic action against ATR-induced nephropathy.(2)LYC iniciates nuclear receptor(AhR, CAR, PXR) response, decreasing the expression of CYP450 subunit gene, changing the content of CYP450, disturbing CYP450 enzymes(APND, ERND, AH, NCR) activities, exerting antagonistic action against ATR-induced abnormal response of nuclear receptor.(3)LYC madulates antioxidant enzyme systems(T-SOD, GSH-Px, CAT) by activation of renal Nrf2 signaling pathway, againsting ATR-induced oxidative stress, then playing antagonistic action against ATR-induced oxidative damage.(4)LYC regulates AMPK(Prkaa1, Prkaa2, Prkab1, Prkab2, Prkag2, Prkag3), Belin1 and ATGs(ATG2b, ATG3, ATG4 b, ATG4 a, ATG4 c, ATG5, ATG7, ATG9 a, ATG9 b, ATG10, ATG13, ATG14, ATG16/1, ATG16/2) gene expression in mice kidney, againsting ATR-induced renal autophagy by activating AMPK pathway in mice.(5)LYC regulates the expression of antioxidant enzymes and p62 by activating Nrf2 signaling pathway, then madulating AMPK pathway to resist ATR-induced renal oxidative stress and autophagy.