Evaluation of the protective effects of Ganoderma applanatum against doxorubicin-induced toxicity in Dalton's Lymphoma Ascites (DLA) bearing mice

Drug Chem Toxicol. 2022 May;45(3):1243-1253. doi: 10.1080/01480545.2020.1812630. Epub 2020 Aug 28.

Abstract

The toxic side effects of doxorubicin in cancer treatment are well established. Here we show that methanolic extract of the fungus Ganoderma applanatum offers protection against cardio- and hepatotoxicity induced by doxorubicin (DOX) in Dalton's Lymphoma Ascites (DLA) bearing mice. Treatment of DLA mice with 20 mg/kg of doxorubicin significantly increased the activities of serum toxicity markers including aspartate amino-transferase (AST), alanine amino-transferase (ALT) and lactate dehydrogenase (LDH). However, co-administration of doxorubicin (20 mg/kg) by intraperitoneal injection and G. applanatum (150 mg/kg) by oral gavage in DLA mice lowered the AST, ALT, and LDH activities when compared to DOX alone treatment. Treatment of DLA mice with DOX alone resulted in reduced GSH contents, and decreased the activities of glutathione-s-transferase (GST), catalase (CAT), and superoxide dismutase (SOD). Treatment of DOX-administered DLA mice with G. applanatum however increased the GSH content and elevated the activities of GST, CAT, and SOD. Among the various solvent extracts of G. applanatum, methanolic extract showed the highest phenolic (376.5 ± 15.24 mg GAE/g) and flavonoid (4717.79 ± 170.22 mg quercetin/g) contents compared to the aqueous (216.3 ± 7.33 mg GAE/g) and chloroform extracts (137.27 ± 1.03 mg GAE/g). Consistently, the methanolic extract was found to possess the highest free radical scavenging activities when compared to the aqueous and chloroform extracts as measured by ABTS and DPPH assays. Our results thus suggest that the protective roles of G. applanatum in DOX-induced toxicity could be an attribute of the antioxidant properties conferred by the high phenolic and flavonoid contents.

Keywords: Dalton’s Lymphoma Ascites; Ganoderma applanatum; antioxidants; cardioprotective; doxorubicin; hepatoprotective; oxidative stress.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Ascites / drug therapy
  • Ascites / pathology
  • Ascites / prevention & control
  • Chloroform / therapeutic use
  • Doxorubicin / toxicity
  • Flavonoids
  • Ganoderma*
  • Lymphoma* / drug therapy
  • Methanol
  • Mice
  • Phenols
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Superoxide Dismutase

Substances

  • Antioxidants
  • Flavonoids
  • Phenols
  • Plant Extracts
  • Chloroform
  • Doxorubicin
  • Superoxide Dismutase
  • Methanol