Rosiglitazone Protects Against Endotoxin-induced Acute Liver Injury In Rats

Object:This study was designated to determine the effects of rosiglitazone onendotoxin-induced acute liver injury in rats. So alanine aminotransferase（ALT）levels，serum aspartate aminotransferase（AST）and interleukin12(IL-12) were determined toassess the effects of rosiglitazone. We also discussed its clinical value.Materials and methods: All the animals were randomly assigned to one of fourfollowing groups (n=24per group). In the LPS-vehicle group, rats were treated with10%dimethyl sulphoxide (DMSO,1ml/kg)30mins before they were challenged withLPS (n=24). In the ROSI-LPS group was identical to the LPS-vehicle group butreceived rosiglitazone (0.3mg/kg intravenously)(n=24).In the sham-vehicle group, ratswere treated with10%(v/v) dimethyl sulphoxide (DMSO,1ml/kg)30mins before theadministration of saline(n=24). The sham-rosiglitazone (ROSI) group was identical tothe sham-vehicle group except that rosiglitazone (0.3mg/kg intravenously) wasadministered instead of DMSO (n=24).Sepsis was induced in rats by dissecting thececum and placing the discontinued organ back into the abdomen (cecum ligation anddissection [CLD]). And all the Rats were decapitated at0h,6h.12h,24h after themodel completed. Serum aspartate aminotransferase (AST), alanine aminotransferase(ALT) levels, and interleukin12(IL-12) were determined to assess activity andliver pathologic change of rats in different groups.Data were analyzed with SPSS13.0software. Student’s t-test was used to compare densitometry data, and statisticalsignificance was defined as P<0.05.Result:SPSS13.0statistical software analysis by the outcome of the application ELASAmethod for determining six hours between the LPS-vehicle group and theROSI-LPS group, there was significant difference（P6=0.000，P12=0.003，P24=0.018，P<0.05）.The LPS-vehicle group and the sham-vehicle group6hours,12hours and24hours the presence of plasma IL-12concentration changes statistically significantdifference (P6=0.000, P12=0.001, P24=0.009, P <0.05).Sepsis IL-12began to increase in6hours,24hours of high-value, no clear peak trend, the ROSI-LPS group comparedwith the LPS-vehicle group had lower concentrations of IL-12to someextent.Description Rosiglitazone inhibit inflammatory cytokines in rats with sepsis roleof IL-12, there is a certain role to reduce the inflammatory response in sepsis.CompareexistALT enzyme concentration the LPS-vehicle group and the ROSI-LPS groupadministered12hours and24hours in plasma statistically significant (P12=0.01,P24=0.00, P <0.05).Between the LPS-vehicle group and the sham-vehicle group0hours,6hoursALT concentrations showed no significant difference (P0=0.108, P6=0.108, P>0.05),12hours,24hours ALT concentrations compare statistical difference(P12=0.000, P24=0.000, P <0.05).Endotoxin-induced acute liver injury elevated ALT6-12hours beginning24hours up to the peak, there was no clear downward trend.TheLPS-vehicle group and the ROSI-LPS group6hours,12hours and24hours thepresence ofAST concentration changes statistically significant difference(P6=0.021,P12=0.018, P24=0.000, P <0.05).The LPS-vehicle group and the sham-vehicle group6hours,12hours and24hours the presence ofAST concentration changes statisticallysignificant difference(P6=0.000,P12=0.002,P24=0.000,P<0.05).Endotoxin-induced acuteliver injury in rats began to increaseAST6-12hours,24hours up to the peak, there isno clear downward trend.Conclusions:Treatment with rosiglitazone, an agonist of peroxisomeproliferator-activated receptors (PPARγ), markedly inhibited the expression of IL-12,attenuated pulmonary inflammation and liver injury caused by sepsis in rat.