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

Environ Toxicol Pharmacol. 2011 Jan;31(1):107-18.
Majumdar S, Karmakar S, Maiti A, Choudhury M, Ghosh A, Das AS, Mitra C. 
Department of Physiology, Presidency College, Kolkata 700 073, India.
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 arsenictransference. 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. Arsenicalso 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.