Octreotide protects doxorubicin-induced cardiac toxicity via regulating oxidative stress. 2018

G-F Dai, and Z Wang, and J-Y Zhang
Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. zejs92@163.com.

To explore the role of octreotide in doxorubicin-induced (DOX) cardiac toxicity in rats, and to investigate its underlying mechanism. 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. 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. Octreotide improves the anti-oxidant capacity of cardiomyocytes via activating the Nrf2 pathway, thereby protecting doxorubicin-induced cardiac toxicity in rats.

UI MeSH Term Description Entries
D008297 Male Males
D004317 Doxorubicin Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN. Adriamycin,Adriablastin,Adriablastine,Adriblastin,Adriblastina,Adriblastine,Adrimedac,DOXO-cell,Doxolem,Doxorubicin Hexal,Doxorubicin Hydrochloride,Doxorubicin NC,Doxorubicina Ferrer Farm,Doxorubicina Funk,Doxorubicina Tedec,Doxorubicine Baxter,Doxotec,Farmiblastina,Myocet,Onkodox,Ribodoxo,Rubex,Urokit Doxo-cell,DOXO cell,Hydrochloride, Doxorubicin,Urokit Doxo cell
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015282 Octreotide A potent, long-acting synthetic SOMATOSTATIN octapeptide analog that inhibits secretion of GROWTH HORMONE and is used to treat hormone-secreting tumors; DIABETES MELLITUS; HYPOTENSION, ORTHOSTATIC; HYPERINSULINISM; hypergastrinemia; and small bowel fistula. Octreotide Acetate,Compound 201-995,Octreotide Acetate Salt,SAN 201-995,SM 201-995,SMS 201-995,Sandostatin,Sandostatine,Sandoz 201-995,Compound 201 995,Compound 201995,SAN 201 995,SAN 201995,SM 201 995,SM 201995,SMS 201 995,SMS 201995,Sandoz 201 995,Sandoz 201995
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D018384 Oxidative Stress A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). Anti-oxidative Stress,Antioxidative Stress,DNA Oxidative Damage,Nitro-Oxidative Stress,Oxidative Cleavage,Oxidative DNA Damage,Oxidative Damage,Oxidative Injury,Oxidative Nitrative Stress,Oxidative Stress Injury,Oxidative and Nitrosative Stress,Stress, Oxidative,Anti oxidative Stress,Anti-oxidative Stresses,Antioxidative Stresses,Cleavage, Oxidative,DNA Damage, Oxidative,DNA Oxidative Damages,Damage, DNA Oxidative,Damage, Oxidative,Damage, Oxidative DNA,Injury, Oxidative,Injury, Oxidative Stress,Nitrative Stress, Oxidative,Nitro Oxidative Stress,Nitro-Oxidative Stresses,Oxidative Cleavages,Oxidative DNA Damages,Oxidative Damage, DNA,Oxidative Damages,Oxidative Injuries,Oxidative Nitrative Stresses,Oxidative Stress Injuries,Oxidative Stresses,Stress Injury, Oxidative,Stress, Anti-oxidative,Stress, Antioxidative,Stress, Nitro-Oxidative,Stress, Oxidative Nitrative,Stresses, Nitro-Oxidative
D032383 Myocytes, Cardiac Striated muscle cells found in the heart. They are derived from cardiac myoblasts (MYOBLASTS, CARDIAC). Cardiomyocytes,Muscle Cells, Cardiac,Muscle Cells, Heart,Cardiac Muscle Cell,Cardiac Muscle Cells,Cardiac Myocyte,Cardiac Myocytes,Cardiomyocyte,Cell, Cardiac Muscle,Cell, Heart Muscle,Cells, Cardiac Muscle,Cells, Heart Muscle,Heart Muscle Cell,Heart Muscle Cells,Muscle Cell, Cardiac,Muscle Cell, Heart,Myocyte, Cardiac
D066126 Cardiotoxicity Damage to the HEART or its function secondary to exposure to toxic substances such as drugs used in CHEMOTHERAPY; IMMUNOTHERAPY; or RADIATION. Cardiac Toxicity,Cardiac Toxicities,Cardiotoxicities,Toxicity, Cardiac

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