Arsenic-induced hepatic mitochondrial toxicity in rats and its amelioration by dietary phosphate.

Abstract

The present study was aimed to test the hypothesis that inorganic phosphate may reduce arsenic toxicity by decreasing its intestinal transference. Co-administration of inorganic phosphate (6.56 M) and arsenic (6.07 mM) in the intestinal loops of rats, in situ, caused significant reduction of arsenic transference. Short-term arsenic exposure (3mg/kg body weight/day for 30 days) caused liver damage evidenced by activities of liver enzymes and necroinflammatory changes. These effects of arsenic were coupled with enhanced mitochondrial swelling, inhibition of cytochrome c oxidase, Ca(2+)-ATPase, a decrease in mitochondrial calcium content, changes in indices of hepatic mitochondrial oxidative stress and iNOS expression. Arsenic also increased hepatic caspase 3 activity and DNA fragmentation. All these apoptosis-related molecular changes caused by arsenic could be alleviated by supplementation with inorganic phosphate, which likely suggests a protective role of phosphate against arsenic-induced hepatotoxic changes.

• Authors: Sangita Majumdar, Subhra Karmakar, Anasuya Maiti, Monalisa Choudhury, Aniruddha Ghosh, Asankur Sekhar Das, Chandan Mitra
• Journal: Environmental toxicology and pharmacology (Environ Toxicol Pharmacol) Vol. 31 Issue 1 Pg. 107-18 (Jan 2011) ISSN: 1872-7077 [Electronic] Netherlands
• PMID: 21787675 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier B.V. All rights reserved.

Chemical References

• Phosphates
• Phosphorus, Dietary
• Poisons
• Nitric Oxide
• Hydroxyl Radical
• Catalase
• Nitric Oxide Synthase Type II
• Superoxide Dismutase
• Caspase 3
• Arsenic

Topics

• Animals
• Arsenic (antagonists & inhibitors, toxicity)
• Arsenic Poisoning (metabolism)
• Caspase 3 (metabolism)
• Catalase (metabolism)
• Chemical and Drug Induced Liver Injury (pathology, prevention & control)
• DNA Fragmentation (drug effects)
• Dietary Supplements
• Hydroxyl Radical (metabolism)
• Intestinal Mucosa (metabolism)
• Lipid Peroxidation (drug effects)
• Liver (pathology)
• Male
• Mitochondria, Liver (drug effects, pathology)
• Mitochondrial Membranes (drug effects)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type II (metabolism)
• Phosphates (therapeutic use)
• Phosphorus, Dietary (pharmacology)
• Poisons (toxicity)
• Rats
• Rats, Wistar
• Superoxide Dismutase (metabolism)