To assess the effect of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors on plasma cholesterol concentrations and on platelet aggregation, lovastatin or fluvastatin, 40 mg daily, was given to hypercholesterolemic patients. After 24 weeks, plasma low-density lipoprotein (LDL) cholesterol concentrations were reduced by 37% after lovastatin therapy and 29% after fluvastatin therapy. The platelet cholesterol/phospholipid ratio was reduced by 33% and 26%, respectively. Platelet aggregation was significantly reduced by 12-15% (p < 0.01) after 4 weeks of therapy with either agent. Lovastatin or fluvastatin therapy reduced platelet aggregation through an in vivo hypocholesterolemic action on the platelet cholesterol content and also through a direct effect on platelet function, as a result of drug binding to the platelets. We also studied the effect of these HMG-CoA reductase inhibitors on LDL susceptibility to oxidation. LDL oxidation (induced by copper ions) was reduced by 31% after lovastatin therapy and by 37% after fluvastatin therapy. The inhibitory effect of HMG-CoA reductase inhibitors on LDL oxidation involved their stimulatory effect on the removal of LDL from the circulation and a direct binding effect of the drugs to the lipoprotein. Because HMG-CoA reductase inhibitors can inhibit platelet aggregation, macrophage foam cell formation, and LDL oxidation, major contributors to atherogenesis, the use of these drugs can significantly attenuate the atherosclerotic process.

Olive oil decreases the accumulation of triglyceride in the liver of rats with NAFLD, but does not provide the greatest antioxidant activity.

The aim of this study was to examine the effect of the antithrombotic drugs aspirin and enoxaparin on fibrosis progression and regenerative activity in a rat model of liver cirrhosis and to determine if these two drugs are beneficial in animals with advanced fibrosis or with established cirrhosis undergoing partial hepatectomy. Thioacetamide-induced cirrhotic rats received saline (N=10), aspirin (N=7), or enoxaparin (N=11) for a 5-week treatment period. Hepatic fibrosis was assessed according to METAVIR score. Liver regeneration was monitored using PCNA immunostaining. Compared to untreated cirrhotic controls, a significant improvement in fibrosis grade was observed in the aspirin (43%; chi(2)=54, P<0.001) and enoxaparin (36%; chi(2)=43, P<0.001) treated groups. Postoperatively, total serum bilirubin levels were lower in the aspirin (1.4+/-0.18 mg/dl; P<0.01) and enoxaparin (1.8+/-0.35 mg/dl; P<0.05)-treated groups compared to untreated cirrhotic controls (3.2+/-0.6 mg/dl). Hepatic regenerative activity was significantly improved in the aspirin group (57.3%+/-6.8%, versus 34.2%+/-7.2% in untreated cirrhotic controls; P<0.01) but unchanged in the enoxaparin group. We conclude that aspirin and enoxaparin hold promise as a useful therapy for patients with extensive fibrosis.

Up to 46% of patients with NAFLD may have thrombotic risk factors, and the presence of thrombotic risk factors is correlated with the extent of hepatic fibrosis, suggesting a crucial role of the coagulation system in the pathogenesis of hepatic fibrosis.