Involvement of reactive oxygen species in Microcystin-LR-induced cytogenotoxicity.

Abstract:

:Microcystin-LR (MCLR) is a potent hepatotoxin. Oxidative stress is thought to be implicated in the cytotoxicity of MCLR, but the mechanisms by which MCLR produces reactive oxygen species (ROS) are still unclear. This study investigated the role and possible sources of ROS generation in MCLR-induced cytogenotoxicity in HepG2, a human hepatoma cell line. MCLR increased DNA strand breaks, 8-hydroxydeoxiguanosine formation, lipid peroxidation, as well as LDH release, all of which were inhibited by ROS scavengers. ROS scavengers partly suppressed MCLR-induced cytotoxicity determined by the MTT assay. MCLR induced the generation of ROS, as confirmed by confocal microscopy with 2-[6-(4'-hydroxy)phenoxy-3H-xanthen-3-on-9-yl]benzoic acid, and upregulated the expression of CYP2E1 mRNA. In addition, CYP2E1 inhibitors chlormethiazole and diallyl dulphide inhibited both ROS generation and cytotoxicity induced by MCLR. The results suggest that ROS contribute to MCLR-induced cytogenotoxicity. CYP2E1 might be a potential source responsible for ROS generation by MCLR.

journal_name

Free Radic Res

journal_title

Free radical research

authors

Nong Q,Komatsu M,Izumo K,Indo HP,Xu B,Aoyama K,Majima HJ,Horiuchi M,Morimoto K,Takeuchi T

doi

10.1080/10715760701704599

subject

Has Abstract

pub_date

2007-12-01 00:00:00

pages

1326-37

issue

12

eissn

1071-5762

issn

1029-2470

pii

783432046

journal_volume

41

pub_type

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