Beneficial Effects of Fluvastatin on Liver Microcirculation and Regeneration After Massive Hepatectomy in Rats

Abstract

Fluvastatin, the first entirely synthetic statin, has a significant cholesterol-lowing effect comparable with other statins. In addition, it has been shown to inhibit oxidative stress and improve vascular endothelial function. The aim of this study was to clarify the pretreatment effects of fluvastatin on liver function after massive hepatectomy in rats. Six-week-old male Wister rats were divided into two groups: a fluvastatin group (group F), pretreated with oral administration of fluvastatin (20 mg/kg per day) for 2 days before 90% hepatectomy; and a control group (group C), pretreated with vehicle for 2 days before hepatectomy. Animals were sacrificed at 0, 12, 24, 48, and 72 h after hepatectomy. The liver regeneration rate, liver function tests, and hepatic stellate cell activation were examined. The liver regeneration rate in group F was significantly higher at 72 h after hepatectomy (P < 0.05). The serum level of total bilirubin in group F was significantly lower at 48 h after hepatectomy (P < 0.05). Sinusoidal area in group F was maintained histologically. Furthermore, the expression of alpha smooth-muscle actin (alpha-SMA) protein in the liver was inhibited in group F at 48 h after hepatectomy. This study demonstrated the beneficial effects of fluvastatin in a lethal massive hepatectomy model using rats, with improved hepatic regeneration and microcirculations, by inhibiting the activation of hepatic stellate cells.

Effects of Bicyclol on Liver Regeneration After Partial Hepatectomy in Rats

“…Original magnification 9100 rats [19]. Previous studies have shown that several factors, such as growth factors, nutritional status, pharmacologic agents, etc., may affect liver regeneration in rats [20,21]. In the present study, bicyclol pretreatment significantly enhanced liver regenerative capacity as indicated by increased liver regeneration rate, PCNA label index, and proliferation index.…”

Multidrug donor preconditioning prevents cold liver preservation and reperfusion injury

“…Statins have been shown to suppress inflammation and proliferation in vascular endothelial and smooth muscle cells [8,39] and to reduce I/R injury in the liver [8] and the kidney [40]. Of interest, the pleiotropic actions of statins are not related to its lipid-lowering mechanism but rather caused by their anti-oxidative properties [17,41], their inhibitory action on leukocyte adhesion [42,43], and their modulatory function on the microcirculation [42,44]. These statin actions may have contributed to the prevention of I/R injury observed in the present study after MDDP application.…”

Heat Shock Protein 90 Inhibitor Induces Apoptosis and Attenuates Activation of Hepatic Stellate Cells

“…This is also clinically applicable because statins are potent stimuli for NO production in sinusoidal endothelial cells (Deleve et al, 2008;Tokunaga et al, 2008), and adjacent HSCs are likely to be exposed to high concentrations of NO. Therefore, in vivo evaluation of 17AAG/statin combination is anticipated as an antifibrotic strategy.…”