Influence of high cholesterol diet and pravastatin sodium on the initiation of liver regeneration in rats after partial hepatectomy.
OBJECTIVE
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.
Zivna
Helena
H
Institute of Physiology, Charles University, University Hospital, Hradec Kralove, Czech Republic. zivny@lfhk.cuni.cz
Zivny
Pavel
P
Palicka
Vladimir
V
Simakova
Eva
E
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D004247:DNA / Q000032:analysis; D006498:Hepatectomy; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008099:Liver / Q000033:anatomy & histology / Q000737:chemistry; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D009929:Organ Size; D017035:Pravastatin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000378:metabolism
D000924:Anticholesteremic Agents; D001786:Blood Glucose; D002791:Cholesterol, Dietary; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014280:Triglycerides; D004247:DNA; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D017035:Pravastatin