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Terminalia muelleri Attenuates the Accumulation of Excess Iron, Inhibition of Topoisomerase 2ß and Oxidative Cardiac Damage in Doxorubicin-Induced Cardiotoxicity in Rats

Terminalia muelleri Attenuates the Accumulation of Excess Iron, Inhibition of Topoisomerase 2ß and Oxidative Cardiac Damage in Doxorubicin-Induced Cardiotoxicity in Rats

Nadia A Eltablawy1, Ibrahim El Tantawy El Sayed2, Hamed Mohamed Abdel Barry2, Marwa A. Ibrahim3*, Maha Nageib Ahmed Serag ElDein2 

1Biochemistry Division, National Organization for Drug Control and Research (NODCAR Egyptian Drug Authority), Egypt; 2Chemistry Department, Faculty of Science, Menoufia University, Shibin El Kom, Egypt; 3Biochemistry and Molecular Biology Dept. Faculty of Veterinary Medicine, Cairo university, Egypt.

*Correspondence | Marwa A Ibrahim, Biochemistry and Molecular biology dept. Faculty of veterinary medicine, Cairo university, Egypt; Email: [email protected] 

ABSTRACT

Background: This work aims to evaluate the protective and attenuating effect of Terminalia Muelleri ethanol extract (TME) against doxorubicin-induced cardiac toxicity. Methods: Total phenolic content (TPC), total flavonoid content (TFC), DPPH. radical scavenging, FRAP and FRAC were determined in the TME extract. Forty-eight adult male Wistar rats were divided equally into six groups: control non-treated, Doxorubicin (DOX) challenge (rats were injected with 2.5 mg/kg of DOX in six injections over 2 weeks), TME was solely administered for four weeks, two weeks pre and two weeks co-administration of TME (100 mg/kg) with DOX as well as TME (100 mg/kg) and TME (200 mg /kg) were administered after two weeks of DOX injection. Results: A relatively high TPC and TFC with considerable antioxidant capacity as evaluated by DPPH, FRAP, and FRAC examinations were recorded. DOX significantly increased serum AST, LDH, CK-MB activities, Troponin1, iron accumulation, and oxidative stress as evidenced by the increased MDA, and NO in association with significant reduction of GSH content in cardiac tissue. Furthermore, mRNA expression of iNOS was significantly upregulated and eNOS and Top 2 ß mRNA expression levels were downregulated. The pre and concomitant administration of TME with DOX as well as the post-administration of TME at 100 and 200 mg /kg suppress the harmful effect of DOX on heart tissue. Conclusion: TME is a potent cardiac protective agent that protects and preserves the heart tissue against the deleterious effect of doxorubicin.

Keywords | Terminalia Muelleri; Doxorubicin; iNOS; eNOS; Top 2 ß 

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Advances in Animal and Veterinary Sciences

December

Vol. 12, Iss. 12, pp. 2301-2563

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