N‐acetylcysteine is more effective than ellagic acid in preventing acrolein induced dysfunction in mitochondria isolated from rat liver

Abstract

Acrolein, a common environmental, food, and water pollutant, has been linked to the pathology of several diseases. This toxic substance is an unsaturated aldehyde and a major component of cigarette smoke and also produced during the processing of fat-containing foods. This study aimed to evaluate the protective effect of ellagic acid and N-acetylcysteine (NAC) in acrolein-induced toxicity in mitochondria isolated from the rat liver. The mitochondria were exposed to different concentrations of acrolein for 40min, then functionality was assessed. Contact with acrolein rapidly and remarkably depleted the intracellular glutathione and antioxidant capacity, because of increased ROS production and lipid peroxidation which may lead to the cell death. Mitochondria were then pre-exposed to different concentrations of ellagic acid, NAC, and IC50 concentration of acrolein. Consistent with the results, acrolein decreased GSH content and increased ROS level and lipid peroxidation, which led to ATP depletion and mitochondrial dysfunction. While ellagic acid has been able to reduce ROS and therefore the permeability of the mitochondrial membrane potential (MMP), presumably via its antioxidant properties, we've not detected its favorable effect on GSH and ATP restoration and also on mitochondrial complex II function. However, NAC strongly decreased ROS, lipid peroxidation and MMP and improved GSH content and complex II activity. These results showed that ellagic acid while reported to possess some cellular protective properties, did not prevent mitochondria from being affected by acrolein during this in vitro study. PRACTICAL APPLICATIONS: Ellagic acid is found in fruits, vegetables, and nuts which are revealed to possess strong antioxidant and protective properties. Mitochondrial dysfunction has been implicated in the pathogenesis of some chronic diseases including cancer, diabetes, liver disease, and neurodegenerative disorders, and presumably, ellagic acid by its mitochondrial protective effects can be helpful in these chronic conditions. Acrolein is an α,β-unsaturated aldehyde that can be produced during cooking at high temperature. By increasing the ROS level and lipid peroxidation and depleting the glutathione content, acrolein induces cellular damage and mitochondrial toxicity. This toxicant is taken into account as a carcinogen and mutagen. In this study, the protective effect of ellagic acid in comparison with N-acetylcysteine has been investigated during the toxicity of acrolein in the rat liver mitochondria to look for evidence of whether it is useful or not through this insult.