The Protective Effect And Mechanism Of Curcumin On The Liver Injury Induced By Heatstroke In Dry-heat Environment In Rats

Objective: To investigate the positive effects of curcumin on liver injury and the possible mechanisms during heatstroke in dry-heat environment in rats.Methods: 160 Sprague-Dawley rats were randomly divided into five groups(n=40): NS,50-cur,100-cur and 200-cur.The NS group were given a gavage of normal saline,while 50-cur,100-cur,200-cur group were given a gavage of curcumin with the concentration 50 mg/kg,100 mg/kg,200 mg/kg once a day for 7 consecutive days.At 8th day,30 rats of each group were transferred to the cabin for heat exposure(The Simulated Climate Cabin for Special Environment of Northwest of China,Urumqi of China)with the conditions of 41±0.5°C temperature,10±1% relative humidity.At the time of 50 th,100th,150 th minute since the experiment began,the rats were detected core temperature(Tc)and anesthetized for collecting blood and liver samples.The other 10 rats of each group were directly detected Tc without heat exposure(the time seem as 0th)and anesthetized for collecting blood and liver samples.Alanine aminotransferase(ALT),aspartate aminotransferase(AST),lipopolysaccharide(LPS)in the blood,malondialdehyde(MDA),superoxide dismutase(SOD),catalase(CAT),cytokines(TNF-?,IL-1?,IL-6,IL-10),nuclear factor-kappa B(NF-?B),inducible nitric oxide synthase(i NOS),intercellular adhesion molecule-1(ICAM-1)and cytochrome-c(Cyt-c)in the liver were detected,histology changes of liver were observed by light microscope and electron microscope.Result:(1)Tc rose with the heat-exposure time in all groups.In NS group,the differences of Tc in different time points were significant(P<0.05).At 150 th,compared with NS group,Tc of curcumin groups decreased(P<0.05).There were no significant differences among curcumin group at 150th(P>0.05).(2)In NS group,compared with 0th,ALT and ALT of 100 th and 150 th increased(P<0.05).At 150 th,compared with NS group,ALT and AST of curcumin groups decreased(P<0.05).The differences were significant among curcumin groups at 150th(P<0.05).(3)In NS group,compared with 0th and 50 th,LPS of 100 th and 150 th increased(P<0.05).At 100 th and 150 th,compared with NS group,LPS of curcumin groups decreased(P<0.05).The differences were significant among curcumin groups at 150th(P<0.05).(4)In NS group,MDA increased,SOD and CAT decreased with the heat-exposure time(P<0.05).At 150 th,compared with NS group,MDA of curcumin groups decreased,SOD and CAT of curcumin groups increased(P<0.05).The differences were significant among curcumin groups at 150th(P<0.05).(5)In NS group,the differences of cytokines(TNF-?,IL-1?,IL-6,IL-10)in different time points were significant(P<0.05).At 100 th and 150 th,compared with NS group,cytokines of curcumin groups decreased(P<0.05).The differences were significant among curcumin groups at 150th(P<0.05).IL-1? and IL-10 were highly correlated in NS group(r=0.926)and curcumin groups(r=0.913).(6)In NS group,compared with 0th,Cyt-c,NF-?B,i NOS and ICAM-1 of 150 th expressed higher and the differences were significant(P<0.05).At 150 th,compared with NS group,Cyt-c,NF-?B,i NOS and ICAM-1 of curcumin groups expressed lower and the differences were significant(P<0.05).The differences were significant among curcumin groups at 150th(P<0.05).In addition,MDA and Cyt-c were correlated(r=897),LPS and NF-?B were correlated(r=0.914),NF-?B and i NOS were correlated(r=0.922).(7)Under light microscope,hepatocyte edema and acidophilia,hepatic sinusoid dilation,central venous thrombosis,and hepatic sinusoid neutrophil infiltration occurred sequentially in NS group with the heat-exposure time while the injury extent of curcumin groups reduced.In NS group,there were significant differences among different time points in the pathological scores(P<0.05).At 100 th and 150 th,compared with NS group,the pathological scores of curcumin groups decreased(P<0.05).The differences were significant among curcumin groups at 150th(P<0.05).(8)Under electron microscope,mitochondria swelled and proliferated with structure damaged and part of nucleus broken in NS group at 150 th,while in curcumin groups,mitochondria proliferated obviously,part of mitochondria swelled but none of structure damaged.