Glutathione monoethyl ester [GSH-MEE] versus N-acetyl cysteine in treatment of acetaminophen-induced hepatotoxicity in mice

ABSTRACT

Acetaminophen [APAP] overdose causes liver injury both in experimental animals and humans. N-Acetylcysteine [NAC] is clinically used as an antidote for APAP intoxication, and it is thought to act by providing cysteine as a precursor of glutathione, which traps a reactive metabolite [N-acetyl-p-benzoquinoneimine [NAPQI]] of APAP. It is believed that glutathione [GSH] itself cannot be used to restore hepatic glutathione as it poorly penetrates hepatic cells. However, Glutathione Monoethyl Ester [GSH-MEE] which is a derivative of GSH has been used often in research to increase intracellular GSH levels. The aim of this work was to evaluate the role Glutathione Monoethyl Ester [GSH-MEE] in treatment of acetaminophen-induced hepatic damage in mice compared with that of N-Acetylcysteine [NAC]. The study was conducted on 60 mice divided into 6 groups, the 1[st] served as the negative control group, the 2[nd] received a single dose of NAC, the 3[rd] received a single dose of GSH-MEE, the 4[th] received acetaminophen in a single toxic dose, the 5[th] received NAC following the toxic dose of acetaminophen and the 6[th] received a single dose of GSH-MEE following the toxic dose of acetaminophen. Serum alanine aminotransferase [ALT] and hepatic glutathione concentration were measured in addition to histopathological examination of the liver. Significant reduction of serum AL T, elevation of hepatic glutathione concentration together with significant regeneration of hepatic cells were noticed following NAC and GSH-MEE administration and it was more noticeable following GSH-MEE intake. GSH-MEE was effective in replenishment of hepatic glutathione pool