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The burden and morbidity of environmental nephrosis is increasing globally. Atrazine (ATR) and degradation products in the environment are considered key determinants of nephrosis. However, the lack of highly effective treatments for environmental nephrosis creates an urgent need to better understand the preventive strategies and mechanisms. This study aimed to highlight the mechanism of ATR-induced environmental nephrosis and the chemoprotective potential of lycopene (LYC) against the renal injury and nephrosis. Male mice were treated with LYC (5 mg/kg) and/or ATR (50 mg/kg or 200 mg/kg) by gavage administration for 21 days. Histopathological changes and biochemical function, cytochrome P450 enzymes system (CYP450s), nuclear xenobiotic receptors (NXRs) response and the transcription of CYP isoforms (CYPs) were detected. ATR exposure caused the changes of the histopathological and biochemical function, activated the NXR response and disturbed the CYP450s homeostasis. Supplementary LYC significantly prevented ATR-induced nephrotoxicity and alleviated the alternation of histopathological and biochemical function via modulating the CYP450s homeostasis and the NXR response. The results demonstrated AHR, CAR, PXR, PPAR (α, γ), CYP1, CYP2, CYP3 and CYP4 superfamily play a vital role in LYC-ATR interaction. Our findings provide new evidence that ATR exposure can cause the environmental nephrosis via inducing the kidney injury. Supplementary LYC showed significant chemoprotective potential against ATR-induced renal injury and environmental nephrosis via regulating the NXR response and the CYP450s homeostasis. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the possible chemoprotective role of lycopene (LYC) against atrazine (ATR)-induced ionic disorder and hepatotoxicity in mice. Male kunming mice were treated with LYC (5mg/kg) and/or ATR (50mg/kg or 200mg/kg) by lavage administration for 21days. Ionic disorder was assessed by determining the Na(+), K(+) and Ca(2+) content and the alteration in ATP enzymes (ATPases) including Na(+)-K(+)-ATPase, Ca(2+)-ATPase, Mg(2+)-ATPase and Ca(2+)-Mg(2+)-ATPase and the mRNA levels of ATPase's subunits in liver. ATR caused the increases of alanine aminotransferase and aspartate aminotransferase activities and histological changes. LYC pretreatment significantly protected liver against ATR-caused alternation. The significant effect of ATR and LYC on the K(+) and Mg(2+) content in liver was not observed, but ATR increased hepatic Na(+)-K(+)-ATPase activity and decreased Mg(2+)-ATPase and Ca(2+)-Mg(2+)-ATPase activity. The mRNA expressions of Na(+)-K(+)-ATPase subunits were regulated significantly by ATR. A significant increase of Ca(2+) content and seven down-regulated mRNA expressions of Ca(2+)-ATPase subunits and a decrease of Ca(2+)-ATPase activity were observed in the ATR-treated mice. Notably, LYC modulated these ATR-induced alterations of ATPase activity and mRNA expression of their subunits. These results suggest that ATR presents hepatotoxicity via regulating hepatic ATPase's activities and their subunit transcriptions and inducing ionic disorder. LYC protects liver against ATR-induced hepatotoxicity, significantly. LYC modulated hepatic ionic homeostasis disturbance via regulation of ATPase activities and their subunits' (1a1, 1b3, 1b4 and 2b4) transcriptions. In summary, these effects play a critical role of LYC-mediated chemoprevention against ATR-induced hepatotoxicity. [ABSTRACT FROM AUTHOR]