ABSTRACT
Objectives To provide theoretical basis for the clinical rational using of drugs, biochemical characteristics of the liver injuries induced by the atorvastatin, simvastatin and lovastatin were analyzed and compared by replicating the rats model of liver injuries induced by statins, Methods 80 SPF SD rats (8 weeks of age), half male and half female, were divided into four groups randomly: control group, simvastatin group, lovastatin group, atorvastatin group. Human equivalent doses were administered to the latter three groups of rats which were sacrificed to draw blood on the 10 th, 35 th and 55 th day respectively (via the femoral artery) for testing liver function index, including total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), aspartateaminotransferase (AST), alanineaminotransferase (ALT), alkalinephosphatase (ALP). Results (1) The increases in TBIL, DBIL, IBIL for treatment group in comparison with control group had statistical significance (P＜0.01).2) At the 55 th day of administration, there was a significant statistical difference between the simvastatin group and the lovastatin group in AST (P＜0.05);3) Meanwhile, there was great statistical difference between the atorvastatin group and lovastatin group in ALP (P＜0.01). Conclusion The rats in the three experimental groups suffered from minor to moderate liver injuries, most of which being cholestasis type. It is speculated that this kind of liver injuries are closely related to the obstacle of transfering bile.
ABSTRACT
Objective To provide theoretical basis for the rational use of drugs in clinic, the biochemical characteristics of liver injury induced by Atorvastatin Combined with HRZ (Isoniazid Rifampicin and Pyrazinamide) were analyzed in animal model. Me thods Eighty 8 week old SPF SD rats with half males and females were divided into four groups: control group, atorvastatin group, HRZ group, atorvastatin+HRZ group. According to the human mouse drug dose conversion, mice were given corresponding drugs by gavage.Hepatic function index of rats (the Total bilirubin, Direct bilirubin, Indirect bilirubin, Aspartate aminotransferase, Alanine aminotransferase, Alkaline phosphatase) were detected by blood from the femoral artery and hepatic function index of rats in each group on 10 d, 20 d, 40 d.Re s ults There were significant difference in the anmmistrated group on 10, 20, 40 days with higher TBIL, DBIL, IBIL than that in control group; in the admimistrated group on Day 10, combined treatment group was higher than that in cotrol group and there were significant differences in ALT;in the process of treatmen, there was statistical difference; ALP was administered for 20 days and the 40 day, atorvastatin there was HRZ group was statistically different in groupHRZ, severe injury, combination group compared with HRZ group had statistically significant difference. Conclus ions The liver injury in the three experimental groups is mild and moderate, and the liver damage is mainly cholestasis type. The most severe hepatic injury caused by Atorvastatin Combined with HRZ is aggravated by the prolonged use of drugs.