Octreotide protects doxorubicin-induced cardiac toxicity via regulating oxidative stress

G.-F. Dai, Z. Wang, J.-Y. Zhang

Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. zejs92@163.com

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• Pharmacology

OBJECTIVE: To explore the role of octreotide in doxorubicin-induced (DOX) cardiac toxicity in rats, and to investigate its underlying mechanism.

MATERIALS AND METHODS: A total of 24 male Sprague Dawley (SD) rats were randomly assigned into 3 groups, including: the control group (NS group), the DOX-induced cardiac toxicity group (DOX group) and the OCT pretreatment + DOX-induced cardiac toxicity group (OCT group). Each group had 8 experimental SD rats. Electrocardiogram was performed in each rat before and after animal procedure, respectively. The serum and heart samples of each rat were collected 10 days after the surgical procedure. Cardiomyocyte apoptosis in the myocardial ischemic area of rats was determined by hematoxylin and eosin (HE) staining and Terminal Deoxynucleotidyl Transferase dUTP Nick-end Labeling (TUNEL) staining. DOX-induced oxidative stress was evaluated by detecting the activities of SOD (superoxide dismutase), MDA (malondialdehyde), GSH (glutathione), T-AOC (total antioxidant capacity) and CAT (catalase). The expression levels of nuclear factor E2 related factor-2 (Nrf2), heme oxygenase-1 (HO-1) and quinone oxidoreductase 1 (NQO1) were detected by Western blot and immunohistochemistry.

RESULTS: Compared with the NS group, heart rate and voltage of QRS wave were both significantly reduced in the DOX group, whereas Q-T interval was significantly prolonged (p < 0.05). Arrhythmia was even found in some rats of the DOX group. However, rats in the OCT group had significantly higher heart rate and voltage of QRS wave, as well as shorter Q-T interval when compared with those of the DOX group (p < 0.05). The levels of plasma CK-MB and LDH were remarkably lower in the OCT group than those of the DOX group. The activities of SOD, GSH, CAT and T-AOC in cardiac homogenate of the OCT group were higher than those of the DOX group. However, MDA activity and ROS level in cardiac homogenate were remarkably reduced in the OCT group when compared with those of the DOX group (p < 0.05). Cardiac pathological lesions were alleviated by OCT pretreatment. Moreover, the expression levels of Nrf2, HO-1 and NQO1 were significantly upregulated in the OCT group than those of the DOX group.

CONCLUSIONS: Octreotide improves the anti-oxidant capacity of cardiomyocytes via activating the Nrf2 pathway, thereby protecting doxorubicin-induced cardiac toxicity in rats.

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