RETRACTED ARTICLE: Chemoprotective Effect of Daphnetin Against Benzene-induced Leukemia via Alteration of CYP2E1.

Abstract

Leukemia is the overproduction of a large number of immature blood cells entering into the peripheral blood due to the malignancy of blood-forming tissues. The modern treatment mechanisms that are associated with leukemia comprise chemotherapy, allogeneic cell transplantation, and radiation therapy that comes with adverse side effects. Thus, medicinal herbs and their bioactive compounds are gaining more attention nowadays toward the treatment of leukemia, owing to their minimal side effects. The current study was aimed to scrutinize the antileukemic effect of daphnetin against benzene-induced leukemia in rats and explore the underlying mechanism of its action. Benzene was used for the induction of leukemia in experimental rats. The rats were divided into different groups and body weight; hematological parameters, DNA fragmentation, and cell cycle regulatory parameter were also estimated. RT-PCR was used for the estimation of mRNA expression of cytochrome P450 2E1 (CYP2E1), a membrane protein widely found in liver cells. Daphnetin-treated rats showed upregulation of body weight as compared to other groups. Moreover, daphnetin reduced the blasts (67.8%) in leukemic rats. It also altered the hematological parameters such as RBC (69.8%), WBC (54.5%), lymphocytes (47.6%), neutrophils (48.9%), monocytes (44.7%), eosinophils (48.7%), and basophils (43.5%), respectively. Daphnetin-treated rats showed an increased level of proteins p21 and p53 and reduced level of cyclins D1 and E. RT-PCR showed an upregulated mRNA expression of CYP2E1 (48.4%) of the daphnetin-treated group as compared to other groups. The current study shows the antileukemic effect of daphnetin and highlights the possibility of its use in leukemia to minimize the side effect of the usual therapy.