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Dyslipidemic Effect of Doxorubicin and Etoposide: A Predisposing Factor for the Antineoplastic Drugs-induced Cardiovascular Diseases

Abstract

Antineoplastic drugs are well known for their abilities to induce varying degrees of toxicities and predispose to cardiovascular related disease states.

This study, therefore evaluates the effects of Doxorubicin (Dox) (3 mg/kg body weight) and Etoposide (Etop) (3 mg/kg body weight) alone and in combinations at 12 and 24 h intervals on plasma lipid profiles and paraoxonase-1. Lipid peroxidation, superoxide dismutase (SOD), glutathione peroxidase (Gpx) and reduced glutathione (GSH) in selected male rat organs were also evaluated. The results were analyzed using One-way ANOVA followed by post hoc tests.

Hypocholesterolemia characterized the effects of Etop alone and in combination with Dox at 12 h, while at 24 h interval hypercholesterolemia was observed in the combined group. Both drugs induced significant hypertriglyceridemia except at 12 h combination with significant hypotriglyceridemia. Individually, the drugs significantly reduced HDL-cholesterol (HDL-C) contrarily to up-regulation when combined. HDL-triacylglycerol, phospholipids and paraoxonase- 1 activities were significantly reduced in all the treated groups, compared with the control. Dox markedly elevated lipid peroxidation in liver and heart, but repressed by Etoposide in the heart and erythrocyte. In combination, Etop at both time intervals ameliorated Dox-induced lipid peroxidation. All treatments elicited significant reduction in liver and erythrocyte GSH levels except heart with significant increase. The treatments significantly depressed hepatic SOD activities while moderating GPx activities in all the organs studied.

This study shows that the derangements in the lipid profile are a common factor for the potential of the both drugs to predispose to cardiovascular diseases than the observed antioxidant status.

Fatoki JO, Adedosu OT, Afolabi OK, Adeleke GE, Adedeji AL, Ige SF, Adesope EO, Oyewole OV, Daramola AD, Badmus JA

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