Hepatitis Research Today is a free monthly online journal that collates and summarizes the latest research about Hepatitis, including details on hepatitis a, b, c, causes, symptoms.

Arsenic induces apoptosis in mouse liver is mitochondria dependent and is abrogated by N-acetylcysteine.

Santra A, Chowdhury A, Ghatak S, Biswas A, Dhali GK

Centre for Liver Research, Department of Gastroenterology, Institute of Post Graduate Medical Education and Research, Kolkata 700020, West Bengal, India. asantra2000@yahoo.co.in

Arsenicosis, caused by arsenic contamination of drinking water supplies, is a major public health problem in India and Bangladesh. Chronic liver disease, often with portal hypertension occurs in chronic arsenicosis, contributes to the morbidity and mortality. The early cellular events that initiate liver cell injury due to arsenicosis have not been studied. Our aim was to identify the possible mechanisms related to arsenic-induced liver injury in mice. Liver injury was induced in mice by arsenic treatment. The liver was used for mitochondrial oxidative stress, mitochondrial permeability transition (MPT). Evidence of apoptosis was sought by TUNEL test, caspase assay and histology. Pretreatment with N-acetyl-L-cysteine (NAC) was done to modulate hepatic GSH level. Arsenic treatment in mice caused liver injury associated with increased oxidative stress in liver mitochondria and alteration of MPT. Altered MPT facilitated cytochrome c release in the cytosol, activation of caspase 9 and caspase 3 activities and apoptotic cell death. Pretreatment of NAC to arsenic-treated mice abrogated all these alteration suggesting a glutathione (GSH)-dependent mechanism. Oxidative stress in mitochondria and inappropriate MPT are important in the pathogenesis of arsenic induced apoptotic liver cell injury. The phenomenon is GSH dependent and supplementation of NAC might have beneficial effects.

Published 9 April 2007 in Toxicol Appl Pharmacol, 220(2): 146-55.
Full-text of this article is available online (may require subscription).

© 2006-2008 Hepatitis Research Today. All Rights Reserved.