Efeitos do disseleneto de difenila sobre o dano oxidativo causado por paracetamol em cérebro de camundongos

Abstract

Acetaminophen (APAP) is the analgesic most used in world, in therapeutic doses does not show toxicity, but in elevated doses can cause hepatic damage due the formation of his metabolic toxic N-acetyl-p-benzoquinonimine (NAPQI). The brain damage can occurs because hepatic damage a condition called hepatic encephalopathy, since the liver already show his function altered, like transform ammonia in urea, causing accumulation of ammonia in the brain, which is toxic for this organ. Furthermore, the NAPQI can cause oxidative damage and mitochondrial dysfunction on brain tissue. The diphenyl diselenide [(PhSe)2] is an organoselenium compound that exhibit antioxidant activity and potential pharmacological. The aim of this study is investigated the ability of (PhSe)2 in reversing the oxidative brain damage and mitochondrial dysfunction induced by a toxic dose of APAP. Mice received a APAP (600mg/kg), followed by a dose of (PhSe)2 (15,6 mg/kg) 1 hour latter. Four hours after APAP administration, plasma was withdrawn from the mice and used for biochemical assays of aspastate aminotransferase (AST) and alanine aminotransferase (ALT) confirming the hepatic damage. The APAP administration increase lipid peroxidation, production of reactive oxygen species and decrease in activity of Na+, K+ - ATPase enzyme. Similary, APAP caused alteration on parameters of mitochondrial function. The treatment with (PhSe)2 revert the cerebral damage induced by a single dose of APAP.