Beneficial effects of fluvastatin on liver microcirculation and regeneration after massive hepatectomy in rats.
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.
Tokunaga
Takuya
T
Department of Surgery, The University of Tokushima, 3-18-15 Kuramoto-cho, 770-8503, Tokushima, Japan.
Ikegami
Toru
T
Yoshizumi
Tomoharu
T
Imura
Satoru
S
Morine
Yuji
Y
Shinohara
Hisamitsu
H
Shimada
Mitsuo
M
D000199:Actins / Q000378:metabolism; D000818:Animals; D001663:Bilirubin / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D000077340:Fluvastatin; D006498:Hepatectomy; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D008099:Liver / Q000098:blood supply* / Q000378:metabolism / Q000601:surgery; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
D000199:Actins; D001663:Bilirubin; D005229:Fatty Acids, Monounsaturated; D000077340:Fluvastatin; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; C498862:Acta2 protein, rat