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Abstract
Pharmaceutical Care and Research: 2019; 19(2):98-101,110
DOI: 10.5428/pcar20190205
Liver injury induced by statins combined with anti-tuberculosis drugs in rats
1. YU Mingli(Department of Pharmacy,Third People’s Hospital of Kunming,Kunming 650041,China 13529017398@163.com)
2. LIU Mengxing(Department of Pharmacy,Third People’s Hospital of Kunming,Kunming 650041,China )
3. LUO Ji(Department of Pharmacy,Third People’s Hospital of Kunming,Kunming 650041,China )
4. CHEN Jie(Department of Pharmacy,Third People’s Hospital of Kunming,Kunming 650041,China )
5. PENG Jiangli(Department of Pharmacy,Third People’s Hospital of Kunming,Kunming 650041,China pengjiangli110@163.com)
ABSTRACT  Objective: To study the characteristics and mechanism of liver injury induced by statins combined with anti-tuberculosis drugs(isoniazid,rifampicin,pyrazinamide),so as to provide theoretical basis for clinical rational use of drugs. Methods:Eighty SD rats were randomly divided into 4 groups by random cluster method: the blank control group,the atorvastatin combined with anti-tuberculosis drugs (isoniazid,rifampicin,pyrazinamide,IRP) group,the simvastatins+IRP group,the lovastatins+IRP group,each consisting 20 rats.The rats in the blank control group were gavaged with normal saline and the rats in the other groups were gavaged with statins combined with anti-tuberculosis drugs according to the dosage conversion table between humans and rats.Blood samples were taken at days 10,35,55 of medication to determine biochemical indexes of liver functions such as aspartate aminotransferase(AST),glutamate aminotransferase(ALT),total bilirubin(TBil),direct bilirubin(DBil),indirect bilirubin(IBil) and alkaline phosphatase(ALP).Meanwhile,hepatic tissues were taken to observe the ultrastructure of hepatic cells under electron microscopy and to analyze the damage of organelles.Results:Compared with the blank control group,the levels of biochemical indexes of liver functions,such as TBil,DBil,IBil in the combination treatment groups increased significantly(P<0.01).In the simvastatin+IRP group and the atorvastatin+IRP group,the levels of AST at 10,35,55 days,the level of ALT at 35 days,the levels of ALP at 35,55 days increased significantly compared with those of the blank control group(P<0.01).With the lengthening of medication time,only the levels of ALP at 35 and 55 days increased significantly(P<0.01) in the simvastatin+IRP group and the lovastatin+IRP group,compared with those of the atorvastatin+IRP group.No statistical significance could be seen,when comparisons were made between the two in the other groups.Electron microscopic observation showed that with the lengthening of medication time,the rats in the statins combined with anti-tuberculosis drugs groups displayed different degrees of hepatic cell damage.Conclusion:Atorvastatin,simvastatin and lovastatin combined with anti-tuberculosis drugs could respectively induce different degrees of liver injury in rats,with cholestasis as the main type,and liver injury tended to be aggravated with the lengthening of medication time.
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Please cite this article as:
YU Mingli,LIU Mengxing,LUO Ji,CHEN Jie,PENG Jiangli,. Liver injury induced by statins combined with anti-tuberculosis drugs in rats[J]. Pharmaceutical Care and Research / yao xue fu wu yu yan jiu. 2019; 19(2): 98-101,110.
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