Omeperazole-induced cytotoxicity in isolated rat hepatocytes

Abstract

Introduction:The liver is central to the metabolism of virtually every foreign substance. Most drugs and xenobiotics are lipophilic, enabling them to cross the membranes of instinal cells. Drugs are rendered more hydrophilic by biochemical processes in the hepatocyte , yielding water – soluble products that are excreted in urine or bile. Most drugs cause liver injury infrequently. Metabolism of a xenobiotic chemical following its exposure can alter it , leading to its detoxification and excretion and/ or enhance its toxicity due to the activation of the compound. The liver is prone to drug-induced hepatotoxicity as it is exposed to high concentrations of drugs and other xenobiotics absorbed from gastrointestinal tract. Omeprazole is used to treat symptoms of gastroesophageal reflux disease (GERD) and other conditions caused by excess stomach acid. It is also used to promote healing of erosive esophagitis . Omeprazole administration is associated with hepatotoxic reactions in some patients. Aim:The aim of this study was the evaluation of cytotoxicity of omeprazole in isolated rat hepatocytes. Method:In this study, the cytotoxic effects of omeprzole was evaluated. Markers such as cell death, reactive oxygen species (ROS) formation, lipid peroxidation , mitochondrial membrane potential , were inversigated. Result: It was found that the drug caused cytotoxicity towards rat hepatocytes concentration – dependently.This study suggests that the adverse effect of studies drug towards hepatocytes is mediated through oxidative stress and the heapatocytes mitochondria play an important role in omeprazole's toxicity. Conclusion:Omeprazole should be administered in patients with hepatic disease with great caution and hepatic functions.and should be monitored regularly in these patients.