Effects of Alcohol and Oxidative Stress on Liver Pathology: The Role of the Mitochondrion

Abstract

This article represents the proceedings of a symposium at the 2001 Research Society on Alcoholism meeting in Montreal, Canada. The chairs were Alan Cahill and Carol C. Cunningham. The presentations were (1) Mitochondrial regulation of ethanol-induced hepatocyte apoptosis: possible involvement of proapoptotic Bcl-2 family protein Bax, by Masayuki Adachi and Hiromasa Ishii; (2) Effects of ethanol on mitochondrial reactive oxygen species production and oxidative protein modification, by Shannon M. Bailey; (3) Acute ethanol binges elicit widespread oxidative mitochondrial DNA damage and depletion: protective effects of antioxidants and inhibitors of ethanol metabolism, by Bernard Fromenty; and (4) Effects of chronic ethanol consumption upon hepatic mtDNA oxidative modification and depletion, by Alan Cahill and Adrian Davies.

Mitochondrial dysfunction and delayed hepatotoxicity: another lesson from troglitazone

“…Examples include valproic acid [33], amiodarone [34][35][36], Wilson's disease [8], Alpers' syndrome [37] and (to some extent) alcohol [7]. These too have similarly pleiomorphic potential, extending from acute hepatitis to cirrhosis.…”

“…It has been described in non-alcoholic steatohepatitis (NASH) [5,6], alcoholic liver disease [7,8] and Wilson's disease [9] to name just a few, but its role in drug-induced liver injury has generally been overlooked (except when accompanied by severe microvesicular steatosis). A recent retrospective study of druginduced liver fatalities was performed using the WHO database [1].…”

The sap of Acer okamotoanum decreases serum alcohol levels after acute ethanol ingestion in rats

“…Enhanced ROS production and compromised antioxidant activity result in oxidative stress, which has been demonstrated to play an important role in alcohol-induced liver injury (15,21). Short-term ethanol intoxication induces oxidative stress, followed by mitochondrial dysfunction and apoptosis in rat hepatocytes (5). It is important to clarify the precise mechanism of ethanol-induced hepatocellular apoptosis and mitochondrial dysfunction, and, in particular, to evaluate the role of the anti-apoptotic protein Bcl-2 and of the pro-apoptotic protein Bax in these mechanisms.…”

Ethanol increases mitochondrial cytochrome P450 2E1 in mouse liver and rat hepatocytes

“…Liver mitochondria are key targets of ethanol toxicity, and mitochondrial dysfunction is known to play a major role in ALD [18][19][20]. One of the mechanisms whereby ethanol could injure mitochondria is via increased generation of ROS and lipid peroxidation products, which could damage key mitochondrial components such as cytochrome c oxidase and mitochondrial DNA [19,21].…”

“…One of the mechanisms whereby ethanol could injure mitochondria is via increased generation of ROS and lipid peroxidation products, which could damage key mitochondrial components such as cytochrome c oxidase and mitochondrial DNA [19,21]. Importantly, oxidative damage to mitochondria can occur whenever the major antioxidant defences (i.e., glutathione, glutathione peroxidase-1 and manganese superoxide dismutase) are overwhelmed within these organelles [20].…”