PROTECTIVE EFFECT OF EXOGENOUS REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE (NADPH) ON DOXORUBICIN INDUCED CARDIOTOXICITY IN ADULT ALBINO RATS Fatma Fawzi Hendawy1 Rabab Fawzy Hindawy2, and Abeer A. Abdelhameed1 Pharmacology Department1, and Forensic Medicine & Clinical Toxicology Department2, Faculty of Medicine, Benha University, Egypt.

Hendawy, Fatma Fawzi; Hindawy, Rabab fawzy; Abdelhameed, Abeer attia

doi:10.21608/ejfsat.2023.164695.1272

	PROTECTIVE EFFECT OF EXOGENOUS REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE (NADPH) ON DOXORUBICIN INDUCED CARDIOTOXICITY IN ADULT ALBINO RATS Fatma Fawzi Hendawy1 Rabab Fawzy Hindawy2, and Abeer A. Abdelhameed1 Pharmacology Department1, and Forensic Medicine & Clinical Toxicology Department2, Faculty of Medicine, Benha University, Egypt.
The Egyptian Journal of Forensic Sciences and Applied Toxicology
Article 9, Volume 23, Issue 2, June 2023, Page 83-99 PDF (895.97 K)
Document Type: Original Article
DOI: 10.21608/ejfsat.2023.164695.1272
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Authors
Fatma Fawzi Hendawy¹; Rabab fawzy Hindawy ²; Abeer attia Abdelhameed¹
¹pharmacology, faculty of medicine, benha university, Egypt
²Forensic medicine and clinical toxicology ,faculty of medicine, Benha university, Benha, Egypt
Abstract
Background: Doxorubicin (DOX) is a potent chemotherapeutic drug that was widely used for treatment of various types of cancer. It produces free radicals which result in extreme dose-limiting cardiotoxicity. Objective: the present study was aimed to investigate the potential cardioprotective effect of exogenous NADPH, against doxorubicin-induced cardiotoxicity in albino rats. Material and Methods: thirty six adult albino rats (180–200 g) were divided into five groups which consist of negative control (group I), positive solvent control (group II), which subdivided into Subgroup IIa (saline): they received normal saline (0.9% NaCl) (solvent of Doxorubicin), and Subgroup IIb (modified saline): they received modified saline with PH:8 (normal saline +10% NaOH) (solvent of exogenous NADPH) Group III (exogenous NADPH): it was given in a dose (8 mg/kg/day) it was given iv/day for 7 days Group IV (Doxorubicin): rats received Doxorubicin in a dose (25 mg/kg), it was given (single dose); i.p. on the 7th day. Group V (Doxorubicin + exogenous NADPH): rats of this group received combination of Doxorubicin which was given in a dose (25 mg/kg) (single dose) i.p. on the 7th day and exogenous NADPH which was given in a dose (8mg/kg/day); iv/day for 7 days. Results: ECG analysis was done before and after treatment. On the 8th day, besides ECG analysis, cTnI, CK-MB, LDH, IL1 β, TNF α, Caspase-3, MDA and GSH were analyzed. Also, histopathological evaluation of isolated hearts was performed by light microscopy. DOX had significantly altered ECG, cTnI, CK-MB, LDH, IL1β, TNFα , Caspase-3, MDA and GSH Pre-treatment with NADPH significantly alleviated DOX-induced ECG changes and also guarded against DOX-induced rise of cTnI, CK-MB, LDH,IL1β, TNF α ,and Caspase-3 levels. NADPH also alleviated histopathological alteration in DOX-treated rats. Moreover, it significantly inhibited DOX-induced GSH depletion and elevation of MDA. Conclusion: It can be mentioned that exogenous NADPH alleviates the doxorubicin-induced cardiotoxicity. NADPH exerts these cardioprotective effects through different mechanisms of antioxidant, antiapoptotic, and anti-inflammatory effects.
Keywords
Cardiotoxicity; Doxorubicin; Exogenous NADPH and Rats


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