Bicuculline methiodide attenuates hepatic injury and decreases mortality in septic rats: role of cytokines

Abstract

Bicuculline methiodide attenuates inflammation by inhibiting the production of proinflammatory cytokines, such as tumor necrosis factor-alpha, and by increasing the production of the anti-inflammatory cytokine interleukin-10, both of which play important roles in the pathogenesis of sepsis. The aim of this study was to examine the effects of bicuculline methiodide on sepsis in the cecal ligation and puncture septic-rat model. Cytokine production was measured by enzyme-linked immunosorbent assay. Oxidative stress was assessed by determining serum lipid peroxidation and nitrite levels. Hepatic injury was evaluated by determining the levels of serum aspartate aminotransferase, alkaline phosphatase, and total bilirubin. Mortality was recorded within 24 h. Bicuculline methiodide potently decreased the production of tumor necrosis factor-alpha and interleukin-1beta but increased interleukin-10 in serum. Bicuculline methiodide significantly decreased serum lipid peroxidation and nitrite levels. Further, bicuculline methiodide attenuated hepatic injury and reduced mortality after cecal ligation and puncture. Therefore, the alteration of cytokine production may be involved in the effects of bicuculline methiodide on hepatic injury and mortality in septic rats.