Calpain in Acute Hepatic Encephalopathy: A Player in Pathophysiology and a Possible Target for Pharmacological Intervention View PDF

^*Mojtaba Farjam
Department Of Medical Pharmacology, School Of Medicine, Fasa University Of Medical Sciences, Fasa, Iran, Islamic Republic Of

^*Corresponding Author:

Mojtaba Farjam
Department Of Medical Pharmacology, School Of Medicine, Fasa University Of Medical Sciences, Fasa, Iran, Islamic Republic Of
Email:mfarjam@sums.ac.ir

Published on: 2014-06-23

Abstract

Acute hepatic encephalopathy (AHE) is a rapidly worsening neuropsychiatric syndrome, secondary to acute liver failure (ALF). In most cases, AHE is fatal without liver transplantation. Extending the survival of AHE patients is clinically important, hoping to find appropriate livers for transplantation. Neuroprotection and hepatoprotection can offer future prospects to achieve this goal. Ammonia which is increased in the brain of AHE patients stimulates the activity of N-methyl-Daspartatre (NMDA) receptors. Based on animal studies reporting beneficial effects of inhibition of these receptors, we hereby suggest that calpain, a Ca2+ -dependent proteolytic enzyme and a downstream mediator of cell injury conferred by over-stimulation of NMDA receptors, can play role in the pathogenesis of brain injury in AHE.

Keywords

Acute hepatic encephalopathy; Neuroprotection; Hepatoprotection; Calpain; Calpain inhibition

Introduction

Acute liver failure (ALF) can precipitate a rapidly worsening neurological syndrome which is clinically called acute hepatic encephalopathy (AHE). Patients suffering from this critical condition are highly susceptible to death. Liver transplantation is the only effective therapeutic intervention to save the lives of the AHE patients. Unfortunately, for many patients, appropriate livers are not available before the disease being irreversibly fatal.