Table of Contents
ISRN Hepatology
Volume 2013, Article ID 817693, 13 pages
http://dx.doi.org/10.1155/2013/817693
Research Article

In Vivo Effect of Arsenic Trioxide on Keap1-p62-Nrf2 Signaling Pathway in Mouse Liver: Expression of Antioxidant Responsive Element-Driven Genes Related to Glutathione Metabolism

1Radiation Genetics and Chemical Mutagenesis Laboratory, Department of Zoology, Centre for Advanced Studies, Visva-Bharati University, Santiniketan, West Bengal 731235, India
2Environmental Toxicology Laboratory, Department of Zoology, Centre for Advanced Studies, Visva-Bharati University, Santiniketan, West Bengal 731235, India
3UGC-DAE Consortium for Scientific Research, Kolkata Centre, 3/LB-8, Bidhan Nagar, Kolkata, West Bengal 700098, India

Received 7 May 2013; Accepted 11 June 2013

Academic Editors: J. J. Marin, Z. Mathe, and Y. Yano

Copyright © 2013 Ritu Srivastava et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Arsenic is a Group I human carcinogen, and chronic arsenic exposure through drinking water is a major threat to human population. Liver is one of the major organs for the detoxification of arsenic. The present study was carried out in mice in vivo after arsenic treatment through drinking water at different doses and time of exposure. Arsenic toxicity is found to be mediated by reactive oxygen species. Nuclear factor (erythroid-2 related) factor 2 (Nrf2)/Keap1 (Kelch-like ECH-associated protein 1)/ARE (antioxidant response element)—driven target gene system protects cells against oxidative stress and maintains cellular oxidative homeostasis. Our result showed 0.4 ppm, 2 ppm, and 4 ppm arsenic trioxide treatment through drinking water for 30 days and 90 days induced damages in the liver of Swiss albino mice as evidenced by histopathology, disturbances in liver function, induction of heat shock protein 70, modulation of trace elements, alteration in reduced glutathione level, glutathione-s-transferase and catalase activity, malondialdehyde production, and induction of apoptosis. Cellular Nrf2 protein level and mRNA level increased in all treatment groups. Keap1 protein as well as mRNA level decreased concomitantly in arsenic treated mice. Our study clearly indicates the important role of Nrf2 in activating ARE driven genes related to GSH metabolic pathway and also the adaptive response mechanisms in arsenic induced hepatotoxicity.