Chronic alcohol consumption increases the sensitivity of rat liver mitochondrial respiration to inhibition by nitric oxide.
Chronic alcohol consumption is a well-known risk factor for hepatic injury, and mitochondrial damage plays a significant role in this process. Nitric oxide (NO) is an important modulator of mitochondrial function and is known to inhibit mitochondrial respiration. However, the impact of chronic alcohol consumption on NO-dependent control of liver mitochondrial function is unknown. This study examines the effect of alcohol exposure on liver mitochondria in a rat model and explores the interaction of NO and mitochondrial respiration in this context. Mitochondria were isolated from the liver of both control and ethanol-fed rats after 5 to 6 weeks of alcohol consumption. Mitochondria isolated from ethanol-treated rats showed a significant decrease in state 3 respiration and respiratory control ratio that was accompanied by an increased sensitivity to NO-dependent inhibition of respiration. In conclusion, we show that chronic alcohol consumption leads to increased sensitivity to the inhibition of respiration by NO. We propose that this results in a greater vulnerability to hypoxia and the development of alcohol-induced hepatotoxicity.
Venkatraman
Aparna
A
Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Shiva
Sruti
S
Davis
Ashley J
AJ
Bailey
Shannon M
SM
Brookes
Paul S
PS
Darley-Usmar
Victor M
VM
D000428:Alcohol Drinking / Q000378:metabolism*; D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects; D019069:Cell Respiration / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000494:pharmacology; D002908:Chronic Disease; D000431:Ethanol / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D010108:Oxyhemoglobins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D002492:Central Nervous System Depressants; D010108:Oxyhemoglobins; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D000431:Ethanol; D014443:Tyrosine