Activating nuclear xenobiotic receptors and triggering ER stress and hepatic cytochromes P450 systems in quails (Coturnix C. coturnix) during atrazine exposure

Abstract

Atrazine (ATR) is one of the most widely detected contaminant in the ecosystem. Nuclear xenobiotic receptors are activated by herbicides and induce the transcription of CYP450 isoforms involved in xenobiotic metabolism and transport. However, little is known about hepatic nuclear xenobiotic receptors in birds are responsible for ATR-induced hepatotoxicity via regulating the cytochrome P450 enzyme systems (CYP450s). The objective of this study was to investigate the mechanism of ATR hepatotoxicity in quails. For this purpose, male quails were dosed by oral gavage from sexual immaturity to maturity with 0, 50, 250, and 500 mg/kg/day ATR for 45 days. The results showed that ATR exposure caused the hepatotoxicity damage and endoplasmic reticulum (ER) degeneration. It suggested that ER is a target organelle of ATR toxicity in hepatocytes. ATR exposure disrupted the hepatic CYP450s homeostasis. This study also demonstrated that ATR triggered the CYP450 isoforms transcription via activating the hepatic CAR/PXR pathway. The present study provides new insights regarding the mechanism of the ATR-induced hepatotoxicity through activating nuclear xenobiotic receptors and triggering ER stress and hepatic CYP450s in quails.

The toxic effects of titanium dioxide nanoparticles on plasma glucose metabolism are more severe in developing mice than in adult mice

“…In a previous study, Hu et al showed that TiO 2 NPs activated a monooxygenase system in mice, as an exogenous compound . Cytochrome P450s, such as Cyp2b9, Cyp2c70, and Cyp4a14, participate in xenobiotic biodegradation and play a primary role in the monooxygenase system . In both developing and adult mice in this study, the TiO 2 NPs increased the expression levels of cytochrome P450s in the early stage, with these effects continuing through the late stage.…”

“…In both developing and adult mice in this study, the TiO 2 NPs increased the expression levels of cytochrome P450s in the early stage, with these effects continuing through the late stage. The overexpression of cytochrome P450s in yeast and HepG2 cells produces responses involved in the unfolded protein response (UPR) and ER stress …”

“…Because of multiple cytochrome P450 isozymes with broad substrate selectivity, a variety of substrates can be oxidized . On one hand, under some abnormal conditions such as ER stress, the monooxygenase system can release superoxide anions and hydrogen peroxide via cytochrome P450s . The continuous production of ROS is an inevitable result of NADPH consumption via microsomal cytochrome P450s .…”

“…[5][6][7] Secondly, the ER is the cellular organelle involved in the synthesis and folding of secreted and membrane-bound proteins. 12,13 An imbalance between the protein folding capacity of the organelle and the functional demand can induce the ER stress. 12,13 More serious ER stress can lead cell apoptosis in the pancreas which reduce the insulin secretion, and the function damages in liver which induce IR.…”

“…12,13 An imbalance between the protein folding capacity of the organelle and the functional demand can induce the ER stress. 12,13 More serious ER stress can lead cell apoptosis in the pancreas which reduce the insulin secretion, and the function damages in liver which induce IR. 13,14 Damage early in life affects a person's normal development and increases adult vulnerability to adversity.…”