[原著] Dose-related effects of atorvastatin on mortality and inflammatory responses to endotoxin-induced shock in rats

Purpose - Statins have been prescribed for dyslipidemia for a long time. Till date, several studies have been conducted on effects of atorvastatin on sepsis; however, dose-related effects have never been investigated. This study evaluated dose-related effects of atorvastatin on endotoxin-induced shock in rats. Methods - Fifty-six male Sprague-Dawley rats were randomly assigned to 1 of the 4 different groups (n = 14 per group): Group C, no medication; group S, oral administration of a small dose of atorvastatin (2 mg/kg/day) for 5 days; group M, oral administration of a medium dose of atorvastatin (5 mg/kg/day) for 5 days; and group L, oral administration of a large dose of atorvastatin (10 mg/kg/day) for 5 days. Following the pretreatment, endotoxin shock was induced by intravenous administration of lipopolysaccharide (15 mg/kg). Hemodynamic recordings, arterial blood gas analyses, and plasma cytokine level measurements were performed regularly. Results - Mortality rates between groups S and C differed significantly (7% and 43%, respectively) at 8 h after lipopolysaccharide injection (P < 0.05). In addition, plasma lactate levels between groups S and C differed significantly at 8 h (P < 0.05). With respect to hemodynamics, the systolic arterial pressure was considerably higher in group S than in the other groups at 8 h after endotoxin injection. Conclusions - A small dose of atorvastatin improved mortality rates and inhibited inflammatory responses to endotoxic shock in rats. These effects were not observed in other doses of atorvastatin, suggesting dose-related effects of atorvastatin on endotoxic shock.