Experimental Study On The Effect Of Collagen Oligopeptide Of Sea Cucumber On The Improvement Of Drug Induced Liver Injury

Objective Anti tuberculosis drugs,rifampicin(RFP)and isoniazid(INH),are common first-line anti tuberculosis drugs,which often cause liver damage.This study was added sea cucumber collagen oligopeptide to observe the effects of rifampicin and isoniazid on liver injury in rats.Methods 72 Male Wistar rats were randomly divided into 6 groups including blank control(A),model-group(B),Positive-control-group(C),the low SCCOPs dose group(D),the medium SCCOPs dose group(E)and the high SCCOPs dose group(F).(each n=12).In the A group were given 0.9% saline(20mg/kg),the remaining five groups' rats were given by gavage INH(50 mg/kg)and RFP(50 mg/kg)once a day,and after two hours,C group was given by gavage silybin 22.1mg/kg,D group was given SCCOPs 346mg/kg.bw,E group was given SCCOPs 692 mg /kg.bw,F group was given SCCOPs 1038mg/kg.bw;the A?B groups were given by gavage physiological saline(20ml/kg),persist for 4 weeks.Then use HE staining to observe the histomorphology and histopathologic grading of liver tissue.Testing alanine aminotransferase(ALT),aspartate transaminase(AST),alkaline phosphatase(ALP),liver index,and the oxidative stress index of rat liver homogenate.Western Blot test was used to detect the expression of TLR4 and NF-kappa B(p65)protein in liver tissues of each group.ELISA was used to detect the concentrations of IL-6,IL-10,TNF-alpha and serum LPS in liver tissue and multiple linear regression analysis was performed on Influencing Factors of liver injury.Results After 4 weeks of anti tuberculosis drugs RFP and INH,the liver tissues of rats(group B)were significantly damaged.Compared with the normal control rats(group A),the average levels of ALT,AST and ALP in the serum of B rats increased by 6.46%,4.80%,and 17.65%,respectively,and the difference was statistically significant(P<0.05).After 4 weeks of collagen oligopeptide(SCCOPs)supplementation,low dose(D),medium dose(E)and high dose(F)SCCOPs supplementation in rats were significantly improved in anti tuberculosis drug liver injury.Compared with group B,the average level of ALT in D and E dose groups decreased by 28.89% and 27.77%respectively(P< 0.05).The expression of TLR4/NF-kappa B(p65)protein in the liver showed that the protein expression in the rat model group,the positive control(C)group and the low,medium and high SCCOPs dose rats were significantly higher than that of the normal control group.Compared with the B group,the protein expression of the low,middle and high SCCOPs doses and the positive control group(silybin supplementation)in the rat was all compared with the B group.Significantly decreased(P<0.05).The results of inflammatory response showed that compared with the normal rats(group A),the levels of IL-6,TNF-alpha and serum LPS increased by 70.12%,75.92%,36.49%,and 91.06% of IL-10 in the model group,and the difference was statistically significant(P <0.05).Compared with the model group,the low,middle and high SCCOPs dose and the positive control group were compared with the model group.The levels of IL-6,TNF-and LPS in liver tissue of rats were significantly decreased(P<0.05),and IL-10 level increased significantly(P <0.05).Multiple linear regression analysis showed that the increase of liver TNF-alpha and serum LPS level in rats was positively correlated with the increase of ALP in liver injury.Conclusion Collagen oligopeptides of sea cucumber can obviously improve the liver injury induced by anti tuberculosis drug.The results of multiple linear regression analysis showed that the level of TNF-alpha and serum LPS in the liver of rats was positively correlated with liver injury.