Abstract
In this study, the protective role of grape seed and skin extract (GSSE) against doxorubicin-induced blood toxicity has been evaluated in rats. Rats were treated with the extract for 8 days and injected with doxorubicin (20 mg/kg) at the 4th day. At the end of the treatment, blood samples were collected for oxidative stress parameters determination and antioxidant enzymes. Doxorubicin increased erythrocytes and plasma malondialdehyde, free iron, H 2 O 2 and carbonylation, decreased calcium and also decreased erythrocytes catalase, peroxidase and superoxide dismutase (specially the Fe isoform). Doxorubicin also decreased plasma catalase and superoxide dismutase (Cu/Zn and Fe isoforms) but increased peroxidase. Doxorubicin increased plasma alanine aminotransferase and aspartate aminotransferase but decreased them within erythrocytes. GSSE co-treatment counteracted almost all deleterious effects induced by doxorubicin. In conclusion, doxorubicin induced a pro-oxidative stress into rat erythrocytes and plasma and GSSE exerted antioxidant properties which can be attributed to free iron and calcium modulation.
Highlights
Doxorubicin (Dox) (Adriamycin) has been used in oncologic practice since the late 1960s
We evaluated the effect of an acute administration of Dox on oxidative stress induced in the blood compartment as well as the putative protection offered by grape seed and skin extract (GSSE)
We found that Dox provoked a drastic oxidative stress status within erythrocytes and plasma as assessed by high MDA and carbonyl protein, elevated AST and ALT within plasma and a drastic depression of anti-oxidant enzymes in both compartments
Summary
Doxorubicin (Dox) (Adriamycin) has been used in oncologic practice since the late 1960s. It held promise as a powerful drug in the fight against cancer (Singal et al, 1998). The clinical efficacy of this drug is limited due to damages toxicity in adults and pediatric cancer patients (Buzdar et al, 1985). The exact causal mechanism of Dox induced toxicity remains unclear, but most of the evidence indicates that free radicals are involved (Singal et al, 1987; Sinha et al, 1987a). Dox administration is associated with a decrease in endogenous anti-oxidants responsible for the scavenging of free radicals (Singal et al, 1995) leading to increased oxidative stress, which is followed by damages in organism (Doroshow et al, 1980)
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