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

Abstract

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.

Authors:
 [1];  [2];  [2];  [2];  [2]
  1. Centre for Liver Research, Department of Gastroenterology, Institute of Post Graduate Medical Education and Research, Kolkata 700020. West Bengal (India). E-mail: asantra2000@yahoo.co.in
  2. Centre for Liver Research, Department of Gastroenterology, Institute of Post Graduate Medical Education and Research, Kolkata 700020. West Bengal (India)
Publication Date:
OSTI Identifier:
20976905
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 220; Journal Issue: 2; Other Information: DOI: 10.1016/j.taap.2006.12.029; PII: S0041-008X(06)00491-1; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ALANINES; AMINOTRANSFERASES; APOPTOSIS; ARSENIC; BANGLADESH; BIOLOGICAL STRESS; CYSTEINE; DISEASE INCIDENCE; DRINKING WATER; GLUTATHIONE; HISTOLOGY; HYPERTENSION; INJURIES; LIVER; LIVER CELLS; MICE; MITOCHONDRIA; MORTALITY; OXIDATION; OXYGEN; PATHOGENESIS; PERMEABILITY; PUBLIC HEALTH

Citation Formats

Santra, Amal, Chowdhury, Abhijit, Ghatak, Subhadip, Biswas, Ayan, and Dhali, Gopal Krishna. Arsenic induces apoptosis in mouse liver is mitochondria dependent and is abrogated by N-acetylcysteine. United States: N. p., 2007. Web. doi:10.1016/j.taap.2006.12.029.
Santra, Amal, Chowdhury, Abhijit, Ghatak, Subhadip, Biswas, Ayan, & Dhali, Gopal Krishna. Arsenic induces apoptosis in mouse liver is mitochondria dependent and is abrogated by N-acetylcysteine. United States. doi:10.1016/j.taap.2006.12.029.
Santra, Amal, Chowdhury, Abhijit, Ghatak, Subhadip, Biswas, Ayan, and Dhali, Gopal Krishna. Sun . "Arsenic induces apoptosis in mouse liver is mitochondria dependent and is abrogated by N-acetylcysteine". United States. doi:10.1016/j.taap.2006.12.029.
@article{osti_20976905,
title = {Arsenic induces apoptosis in mouse liver is mitochondria dependent and is abrogated by N-acetylcysteine},
author = {Santra, Amal and Chowdhury, Abhijit and Ghatak, Subhadip and Biswas, Ayan and Dhali, Gopal Krishna},
abstractNote = {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.},
doi = {10.1016/j.taap.2006.12.029},
journal = {Toxicology and Applied Pharmacology},
number = 2,
volume = 220,
place = {United States},
year = {Sun Apr 15 00:00:00 EDT 2007},
month = {Sun Apr 15 00:00:00 EDT 2007}
}
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