Influence of high cholesterol diet and pravastatin sodium on the initiation of liver regeneration in rats after partial hepatectomy

OBJECTIVES: Liver regeneration is influenced by cholesterol and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA-reductase). HMG-CoA-reductase is a key enzyme for cholesterol synthesis. Recent studies have shown that inhibitors of HMG-CoA-reductase improve liver functions after 67% partial hepatectomy (PH). METHODS: Male Wistar rats (W) and Prague hereditary hypercholesterolemic rats (PHHC) were used. Aqua pro injectione (AI) or pravastatin (prava; 1 mg/kg) was administered orally once daily. Group 1: W, standard diet (SD) + AI; group 2: W, SD + prava; group 3: W, cholesterol-enriched diet (chol) + AI; group 4: PHHC, chol + AI; group 5: PHHC, chol + prava. After 27 d, PH was performed in all groups. RESULTS: Groups fed chol before PH had significantly higher liver triacylglycerol content (group 3: 25.8 ± 2.6 mg/g of liver weight; group 4: 16.0 ± 1.0 of liver weight; group 5: 22.0 ± 1.0 of liver weight) than did the groups fed SD (group 1: 6.1 ± 0.5; group 2: 5.9 ± 0.7). Liver DNA synthesis after PH was significantly lower in chol-fed groups (group 3: 561 ± 78; group 4: 472 ± 92) than in SD-fed groups (group 1: 1645 ± 574; group 2: 2935 ± 1298), except the chol-fed PHHC given prava (group 5: 3230 ± 527). CONCLUSIONS: In prava-treated rats, the induction of HMG-CoA activity overcame the inhibitory capability of pravastatin. The induction of HMG-CoA-reductase activity had a stimulatory effect on the initiation of liver regeneration.