Magnolol alters the course of endotoxin tolerance and provides early protection against endotoxin challenge following sublethal hemorrhage in rats.

Abstract

The endotoxin tolerance induced by sublethal hemorrhage (SLH) is associated with an initial surge of proinflammatory cytokines such as TNF-alpha. Magnolol, a potent antioxidative herb, is hypothesized to suppress TNF-alpha production after SLH and to alter or attenuate subsequent endotoxin tolerance. A prospective, randomized experimental study was performed. Male Sprague-Dawley rats were randomly segregated into one of four groups. Rats in the Sham/Veh and Sham/Mag groups received a sham operation for SLH and treatment with vehicle or magnolol, respectively. Rats in the SLH/Veh and SLH/Mag groups received SLH and treatment with vehicle or magnolol, respectively. Animals were subjected to endotoxin challenge (EC) at 12, 24, or 36 h after these procedures. Cytokines (TNF-alpha and IL-10), lipid peroxidation, and superoxide dismutase (SOD) activity were measured in lung tissue following SLH. Plasma cytokines were assessed after SLH or EC at different time points, and survival analyses were performed after EC. Plasma and tissue TNF-alpha increased after SLH; this increase was significantly suppressed by magnolol. Additionally, a significant increase in plasma and tissue IL-10 after SLH was observed in the SLH/Mag group. Lipid peroxidation and SOD activity increased after SLH; magnolol suppressed the lipid peroxidation but not the SOD activity. If EC was performed 12 or 24 h after SLH, greater survival with decreased TNF-alpha and increased IL-10 in plasma was observed in the SLH/Mag group. If EC was performed 24 or 36 h after SLH, greater survival with decreased plasma TNF-alpha was observed in the SLH/Veh group. In conclusion, magnolol induces an antiinflammatory response and provides early protection against EC following SLH; however, magnolol attenuates the protraction of endotoxin tolerance and inhibits late protection against EC following SLH.