Phoenix Dactylifera L (Aracaceae) Dried Fruits Methanol Extract Protects Doxorubicin Induced Cardiotoxicity by Abrogation of Oxidative Stress and Inflammation in Rats

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Abstract

Doxorubicin (DOX), a cardiotoxic antineoplastic, disrupts both cancerous and non-cancerous cells. Phoenix dactylifera extracts are used to treat various ailments including cancer in Southern Nigeria. This study investigated the chemoprotective properties of P. dactylifera dried fruit methanol extract (PDDFME) on free radical scavenging, cardiac integrity, oxidative stress, and inflammation in DOX-mediated cardiotoxicity. Rats were pre-treated orally for seven days with two doses (1,000 and 2,000 mg/kg) of PDDFME before single DOX (20 mg/kg, i.p.) administration. The rats were euthanized; blood and hearts were removed, and assessed for serum enzymes, histological dynamics, oxidative stress, and inflammatory biomarkers. PDDFME total phenolic contents were 9 times more than the total flavonoid contents. The IC50 for scavenging 2,2’-azinobis-(3-ethylbenzothiazoline-6-sulphonic acid) radical cation and nitric oxide radical, were 2.67 mg and 0.28 mg, respectively. Pre-treatment of PDDFME (at both doses) significantly (p<0.05) attenuated DOX-mediated increases in the activities of serum creatine kinase (CK) and lactate dehydrogenase (LDH); cardiac levels of CK, LDH, malondialdehyde, NO, and TNF-α; and significantly (p<0.05) reversed DOX-induced decreases in the cardiac activities of glutathione-S-transferase, superoxide dismutase, catalase and glutathione peroxidase; and interleukin-10 level. Only the 1,000 mg/kg PDDFME significantly (p<0.05) mitigated the DOX-induced decreases in cardiac glutathione level and glutathione reductase activity. Distinct improvements in cardiac architecture and integrity were observed in PDDFME pre-treatment when compared with the group that received DOX alone. Finally, different doses of PDDFME can prevent DOX-induced free radical generation, cardiomyocyte dysfunction, oxidative stress as well as inflammatory perturbations in rats when pre-administered

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