Alteration in the expression of cytochrome P450s (CYP1A1, CYP2E1, and CYP3A11) in the liver of mouse induced by microcystin-LR.

Bangjun Zhang,Xiaoyu Li,Yang Liu

doi:10.3390/toxins7041102

Abstract

Microcystins (MCs) are cyclic heptapeptide toxins and can accumulate in the liver. Cytochrome P450s (CYPs) play an important role in the biotransformation of endogenous substances and xenobiotics in animals. It is unclear if the CYPs are affected by MCs exposure. The objective of this study was to evaluate the effects of microcystin-LR (MCLR) on cytochrome P450 isozymes (CYP1A1, CYP2E1, and CYP3A11) at mRNA level, protein content, and enzyme activity in the liver of mice the received daily, intraperitoneally, 2, 4, and 8 µg/kg body weight of MCLR for seven days. The result showed that MCLR significantly decreased ethoxyresorufin-O-deethylase (EROD) (CYP1A1) and erythromycin N-demthylase (ERND) (CYP3A11) activities and increased aniline hydroxylase (ANH) activity (CYP2E1) in the liver of mice during the period of exposure. Our findings suggest that MCLR exposure may disrupt the function of CYPs in liver, which may be partly attributed to the toxicity of MCLR in mice.

Highlights

Microcystins (MCs) are the most commonly detected cyanobacterial toxins produced mainly by the cyanobacterium Microcystis in eutrophic lakes, ponds, and rivers throughout the world [1]
The present study aimed to evaluate an integral situation of three major Cytochrome P450s (CYPs) subfamilies, CYP1A1, CYP2E1, and CYP3A11, simultaneously in mouse liver following intraperitoneal (i.p.) exposure of MCLR for seven days
Our results showed that MCLR significantly increased CYP2E1 mRNA level, protein content, and aniline hydroxylase (ANH) activity in mouse liver

Summary

Introduction

Microcystins (MCs) are the most commonly detected cyanobacterial toxins produced mainly by the cyanobacterium Microcystis in eutrophic lakes, ponds, and rivers throughout the world [1]. MCs have over 80 known structural variants, of which microcystin-LR (MCLR) is the most toxic variant found in the aquatic environment [2] These toxins have been shown to cause severe harmful effects in aquatic organisms and humans. The toxicity mechanism of MCs is attributed to their activity as potent inhibitors of serine/threonine protein phosphatases 1 (PP1) and PP2A in liver [3]. This inhibition leads to the hyperphosphorylation of cytoskeleton protein and destroys its components, which induces hepatocyte deformation, dissociation, and necrosis, and causes intrahepatic hemorrhage and death [4,5]. Žegura et al [17] found that the genotoxicity of MCLR was mediated by ROS in human hepatoma

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