Background and Purpose Doxorubicin is a broad-spectrum antineoplastic
agent; however, however, its genotoxic/cytotoxic effects limit its
clinical application. Dimethyl fumarate (DMF) is an FDA-approved oral
drug shown to have antioxidant, anti-inflammatory and antimutagenic
effects via activating Nrf2 antioxidant pathway. The present study aimed
to investigate the possible protective effect of DMF against
doxorubicin-induced chromosomal and DNA damage in rat bone marrow cells.
Experimental Approach Wistar Albino rats of both sexes were administered
DMF orally (15mg/kg once daily for 14 days) alone or with doxorubicin
which was injected as a single dose (90 mg/kg at day 14) to induce
toxicity. The blood samples were collected 24 hours after doxorubicin’s
injection from all groups to measure the serum levels of MDA, GSH, SOD,
and GPx1 and bone marrow was harvested to assess chromosomal aberration,
micronucleus, and comet assays. Key Results The rats in the
doxorubicin-only group exhibited a significant decrease in mitotic index
and depleted GSH and antioxidants enzymes serum levels with a
significant elevation in MDA serum level, % DNA in Tail, micronucleus
appearance and chromosomal aberrations compared to the control group;
DMF pretreatment prior to doxorubicin exposure, significantly-reduced %
DNA in Tail, micronucleus appearance, and chromosomal aberrations,
improved mitotic index, restored GSH level and antioxidant enzymes
activity compared doxorubicin-only group. Conclusion and Implication
This study revealed that DMF alone has no DNA-damaging or clastogenic
activities; DMF has protective effects against the genotoxicity induced
by doxorubicin; thus, DMF might be a potential chemoprotective agent
against doxorubicin-induced toxicity in cancer chemotherapy