Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Effect of styrene oxide and diethyl maleate on expression of cytochrome P450 family 1 and glutathione store in mouse liver

Waranya Chatuphonprasert^1,2 , Kanokwan Jarukamjorn²

¹Faculty of Medicine, Mahasarakham University, Maha Sarakham 44000; ²Research Group for Pharmaceutical Activities of Natural Products using Pharmaceutical Biotechnology Research Group, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand.

For correspondence:- Kanokwan Jarukamjorn Email: kanokwan.ja@kkumail.com Tel:+6643202378

Accepted: 23 January 2021 Published: 28 February 2021

Citation: Chatuphonprasert W, Jarukamjorn K. Effect of styrene oxide and diethyl maleate on expression of cytochrome P450 family 1 and glutathione store in mouse liver. Trop J Pharm Res 2021; 20(2):231-237 doi: 10.4314/tjpr.v20i2.2

© 2021 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To determine the effect of the glutathione (GSH) suppressors styrene oxide (SO) and diethyl maleate (DEM) on the hepatic expression of cytochrome P450 family 1 (Cyp1) isoforms that are related to carcinogenesis including Cyp1a1, Cyp1a2, and Cyp1b1.

Methods: Seven-week-old ICR mice were intraperitoneally injected with SO (150 and 300 mg/kg/day), DEM (175 and 350 mg/kg/day), or N-acetylcysteine (NAC; 300 and 600 mg/kg/day) for 7, 14, or 28 days. Plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, hepatic Cyp1 expression, total glutathione, reduced glutathione (GSH), and oxidized glutathione (GSSG) were determined.

Results: ALT and AST levels were markedly increased by SO and DEM while GSH/GSSG ratio was decreased by SO in all treatments (p < 0.05), while high dose (350 mg/kg/day) DEM significantly suppressed GSH/GSSG ratio at 28 days (p < 0.05). The expressions of Cyp1a1, Cyp1a2, and Cyp1b1 were induced by SO and DEM, corresponding with induction of ethoxy/methoxy-resorufin O- dealkylase activities.

Conclusion: The Cyp1 family metabolizes procarcinogens to carcinogenic DNA adducts; exposure to the industrial solvents, SO and DEM, raises the risk of carcinogenesis via GSH depletion coupled with Cyp1 induction.

Keywords: GSH, Carcinogenesis, Diethyl maleate, N-acetylcysteine, Cytochrome P450 family 1, Hepatotoxicity