Effects of tert-butyl hydroperoxide on Ca2+ ATPase activity in isolated rat hepatocytes and its reversal by antioxidants.

ABSTRACT

Calcium ions play an important role in various physiological processes such as nerve impulse transmission, muscle contraction, hormone action, blood clotting. They ions act as an intracellular second messenger, relaying information within cells to regulate their activity. To understand the mechanism of hepatotoxicity of t-BHP, studies were carried out using freshly isolated rat hepatocytes. The effect of t-BHP on Ca2+ accumulation and Ca2+ uptake by rat hepatocytes was monitored using 45Ca2+. It caused decrease in 15% accumulation of 45Ca2+ in comparison to the control group. t-BHP also significantly decreased the Ca2+ ATPase activity in isolated hepatocytes. This decrease in Ca2+ATPase activity by t-BHP was reversed 40% by naturally occurring antioxidant glutathione (GSH) and 20% by the synthetic antioxidant butylated hydroxy toluene (BHT). These results indicate that the hepatotoxic action of t- BHP involves oxidative stress as evident by the protection accorded by various antioxidants employed in the study as well as impairment of intracellular calcium homeostasis which can lead to liver cell injury.