title: Pentoxifylline abrogates cardiotoxicity induced by the administration of a single high dose or multiple low doses of doxorubicin in rats.
abstract: Doxorubicin (DOX) possesses a broad-spectrum antineoplastic activity; however, its clinical application is impeded by cardiotoxicity. This study aimed to investigate the protective effect of pentoxifylline (PXF), which possesses antioxidant and anti-inflammatory properties against cardiotoxicity induced by a single high dose (15 mg/kg, i.p.) or multiple low doses (2.5 mg/kg, i.p., three times per week for 2 weeks) of DOX. At the end of the experimental period, the serum creatine kinase (CK)-MB and lactate dehydrogenase (LDH) activities were measured. The hearts were then removed for evaluating TNF-α, NO, malondialdehyde (MDA), and reduced glutathione (GSH) levels, superoxide dismutase (SOD) and catalase (CAT) activities, and the expression of iNOS, NF-κB, Fas ligand (FasL), and caspase-3. The administration of DOX in both dose regimens caused increases in serum CK-MB and LDH activities, in cardiac TNF-α, NO and MDA levels, as well as in the cardiac expression of iNOS, NF-κB, FasL and caspase-3, whereas it significantly reduced the cardiac GSH level, as well as SOD and CAT activities (P < 0.05). Prophylactic treatment of rats with PXF diminished DOX-induced alterations in theses parameters. Our results warrant the clinical use of PXF as an adjuvant therapy to abrogate cardiotoxicity of DOX and extend its clinical applications.
authors.affiliation: a Department of Pharmacology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt.
authors.forename: Shimaa M
authors.initials: SM
authors.lastname: Elshazly
authors.affiliation: a Department of Pharmacology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt.
authors.forename: Amr A A
authors.initials: AAA
authors.lastname: Mahmoud
authors.affiliation: a Department of Pharmacology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt.|b Department of Pharmacology, Faculty of Pharmacy, Tabuk University, Tabuk 71491, Kingdom of Saudi Arabia.
authors.forename: Waleed
authors.initials: W
authors.lastname: Barakat
keywords: cardiotoxicity; cardiotoxicité; doxorubicin; doxorubicine; inflammation; oxidative stress; pentoxifylline; stress oxydatif