Current Science

Li-juan Shen ¹, Yong-hua Zhou ², Jin-gui Wang ³, Lan Li ⁴, Shu Lu ⁵

Affiliations
1 Department of ICU, Wuxi Hospital of Traditional Chinese Medicine, Wuxi Affiliated Hospital Nanjing University of Traditional Chinese Medicine, Wuxi 214071, Jiangsu, CN
2 Jiangsu Institute of Parasitic Diseases, Key Laboratory on Technology for Parasitic Disease Prevention and Control, Ministry of Health, Jiangsu Provincial Key Laboratory on Molecular Biology of Parasites, Jiangsu Provincial Key Subject on Parasitic Diseases, Wuxi 214064, CN
3 Department of Medical Affairs, Wuxi Hospital of Traditional Chinese Medicine, Wuxi Affiliated Hospital Nanjing University of Traditional Chinese Medicine, Wuxi 214071, Jiangsu, CN
4 Department of Ultrasonography, Wuxi Hospital of Traditional Chinese Medicine, Wuxi Affiliated Hospital Nanjing University of Traditional Chinese Medicine, Wuxi 214071, Jiangsu, CN
5 Department of Cardiology, Wuxi Hospital of Traditional Chinese Medicine, Wuxi Affiliated Hospital Nanjing University of Traditional Chinese Medicine, Wuxi 214071, Jiangsu, CN

Abstract

The present study aimed to observe the effect of perindopril on cardiac function in doxorubicin-induced cardiotoxicity rats and explore the underlying molecular mechanisms. We constructed a doxoru-bicin-induced cardiotoxicity rat model (1.0 mg kg^–1, biweekly) for six weeks. Rats in the doxorubicin-induced cardiotoxicity group exhibited impaired car-diac function, disorganized sarcomeres and increased levels of brain serum natriuretic peptide, creatine kinase isozyme MB and troponin I. In addition, com-pared to normal hearts, doxorubicin-induced cardio-toxicity hearts exhibited significantly higher levels of angiotensinogen, angiotensin II (Ang II), angiotensin II type 1 receptor, protein kinase C, reactive oxygen species (ROS), high mobility group box 1 (HMGB1), nuclear factor kappa B, tumour necrosis factor-, interleukin-6 as well as interleukin-1. Positive corre-lation was found among Ang II, ROS and HMGB1. After treatment with an angiotensin-converting enzyme inhibitor perindopril, cardiac function and inflammation induced by doxorubicin had distinctly improved. Intriguingly, the levels of Ang II, ROS and HMGB1 decreased significantly. Our findings suggest that perindopril improves cardiac function in doxoru-bicin-induced cardiotoxicity rats, which might be related with Ang II/ROS/HMGB1.

Keywords

Cardiac Function, Doxorubicin-Induced Cardiotoxicity, Myocardial Injury, Perindopril, Rat Model, Reactive Oxygen Species.

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