URSODEOXYCHOLATE PROTECTS AGAINST ETHANOL-INDUCED LIVER MITOCHONDRIALINJURY

The purpose of this work was to examine whether ursodeoxycholate (UDC) , a hydrophilic bile salt, could reduce mitochondrial liver injury fro m chronic ethanol consumption in rats. Animals were pair-fed liquid di ets containing 36% of calories as ethanol or isocaloric carbohydrates. They were randomly assigned into 4 groups of 7 rats each and received a specific treatment for 5 weeks : control diet, ethanol diet, contro l diet + UDC, and ethanol diet + UDC. Respiratory rates of isolated li ver mitochondria were measured using a Clark oxygen electrode with sod ium succinate as substrate. Mitochondria from rats chronically fed eth anol demonstrated an impaired ability to produce energy. At the fatty liver stage, the ADP-stimulated respiration (V3) was depressed by 33%, the respiratory control ratio (RC) by 25% and the P/O ratio by 15%. I n ethanol-fed rats supplemented with UDC, both the rate and efficiency of ATP synthesis via the oxidative phosphorylation were improved : V3 was increased by 35%, P/O by 8%. All the respiratory parameters were similar in control group and control + UDC group. On the other hand, t he number and size of mitochondria were assessed by electron microscop y and computer-assisted quantitative analysis. The number of mitochond ria from ethanol-treated rats was decreased by 29%, and they were enla rged by 74%. Both parameters were normalized to control values by UDC treatment. These studies demonstrate that UDC has a protective effect against ethanol-induced mitochondrial injury by improving ATP synthesi s and preserving liver mitochondrial morphology: These UDC positive ef fects may contribute to the observed decrease In fat accumulation and may delay the progression of alcoholic injury to more advanced stages.