Ulinastatin reduces myocardial injury induced by doxorubicin in SD rats

J.-G. Zhu, K. Jin, Y. Ren

Department of Cardiology, Taizhou People’s Hospital, Jiangsu, China. xhdyzjg@post.usts.edu.cn

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• Pharmacology

OBJECTIVE: The aim of this study was to observe the protective effect of Ulinastatin on myocardial injury induced by doxorubicin (DOX) in rats.

MATERIALS AND METHODS: 30 male Sprague Dawley (SD) rats were divided into control group, DOX group, and Ulinastatin group by random number table method. The control group was intraperitoneally injected with saline, while the DOX group and the Ulinastatin group were injected intraperitoneally with DOX (2 mg/kg) once every other day to establish an acute myocardial injury (AMI) model. In the Ulinastatin group, Ulinastatin (1500 IU/100 mg) was injected intraperitoneally once a day for 2 weeks after the model was established. The changes in cardiac structure were observed with a light microscope, the changes in cardiac function in rats were detected with biochemical kits, and expression of oxidative stress and inflammatory response-related factors were detected by Western blotting, enzyme-linked immunosorbent assay (ELISA), and quantitative Real Time-Polymerase Chain Reaction (qRT-PCR).

RESULTS: Myocardial tissues in the control group were neatly arranged and dense, with complete and clear structure. The myocardial tissues in the DOX group were disorderly arranged, the interstitial fibrosis was evident, and the myocardial transverse striations broke and disappeared. The structure of tissues in Ulinastatin group was dramatically relieved compared with DOX group. The serum SOD and GSH-Px levels of the DOX groups were significantly lower than those of the control group, while the levels of MDA and ROS were dramatically higher than those of the control group. The serum SOD and GSH-Px level of Ulinastatin group were higher than that of DOX group, and the levels of MDA and ROS were lower than those of DOX group. LDH, AST, ALT, and CK levels were dramatically higher than those in the control group, while the above-mentioned serum myocardial zymogram levels in the Ulinastatin group were decreased. The expressions of IL-1β, IL-6, TNF-α, and iNOS in the DOX and Ulinastatin groups were dramatically higher than those in the control group, while the expressions of the above inflammatory factors in the Ulinastatin group were all inhibited.

CONCLUSIONS: Ulinastatin intervention can reduce myocardial injury in rats with DOX. The protective effect may be due to the elimination of oxygen free radicals, enhanced antioxidant enzyme activity, reduced lipid peroxidation and inflammatory responses, and thus repaired myocardial injury.

 

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