Ganoderma applanatum (Pers.) Pat. augments antitumor activity of doxorubicin and provides chemoprevention to murine tumor model

Abstract

Doxorubicin (DOX) is a chemotherapeutic drug, used widely in the treatment of a variety of solid and hematological malignancies. However, its clinical utility is markedly reduced by dose-dependent cardiotoxicity. In the present study, Dalton lymphoma Ascites (DLA) cell line was administered to create a solid tumor in a murine model. DOX (25 mg/kg body wt.) was administered intraperitoneally in overnight fasted Swiss albino mice to induce cardiac toxicity and hepatotoxicity. Thirty minutes before administering the chemotherapeutic drug, water-alcohol extract of the medicinal mushroom Ganoderma applanatum (GAWE) was administered to allotted groups. After five days, the extent of heart damage was analyzed by Electrocardiogram (ECG), further blood serum parameters, such as SGOT, SGPT, ALP, CK-MB, and LDH as well as antioxidants, such as GSH, GPx and tissue peroxidation by MDA level was determined for both liver and heart tissues. The mode of prevention by the mushroom extract from the damage caused by DOX at the molecular level and aberrations in tissue morphology by histopathology was also analyzed. The increase in blood serum parameters and MDA levels were significantly reduced with the GAWE administration. GAWE also upregulated heart and liver antioxidant enzymes and reduces ST, QT interval, and QRS complex, and increased heart rate as compared to DOX treated group. GAWE dose-dependently mitigated DOX-induced cellular discrepancies as evidenced by gene expression study and histological analysis. Hence, it can be concluded that the water-alcohol extract of Ganoderma applanatum (GAWE), is a potent candidate for adjuvant chemotherapy in cancer treatment as it effectively mitigated organ system drug-induced toxicities.