The protective effect of ethanol leaf extract of Annona muricata against doxorubicin toxicity via modulations of hematological, serum biochemical, antioxidant enzymes, and lipid peroxidation

Abstract

BackgroundDoxorubicin (DOX)-induced organ toxicity is of critical concern in cancer therapy because of its contributions to morbidity and mortality of cancer patients. This study evaluated the beneficial effect of Annona muricata (A. muricata) ethanol leaf extract on the toxic effect of DOX. MethodsScavenging abilities of A. muricata fractions (chloroform, ethyl acetate, ethanol, methanol, and aqueous) were tested against 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals. Male rats (Rattus norvegicus) were randomly allotted into four groups of treatments. Group A served as a control, Group B was treated with 2.5 mg/kg body weight (b.w) DOX intraperitoneally (i.p) twice per week, Group C was treated with 200 mg/kg b.w extract (orally), once per day, and 2.5 mg/kg b.w DOX (i.p) twice per week. While Group D was treated with 200 mg/kg b.w. ethanol leaf extracts orally once daily for 2 weeks. Hematological indices (White blood cells (WBC), Red blood cells (RBC), Platelet (PLT), lymphocyte (LYM), hemoglobin (HGB), and hematocrit (HCT)), serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, lactate dehydrogenase (LDH), creatine kinase (CK), cholesterol, CA (SOD), catalase (CAT), reduced glutathione (GSH) and malondialdehyde (MDA) were evaluated. ResultsAqueous and ethanol fractions displayed significant DPPH (p < 0.05) and ABTS (P < 0.05) inhibitory activity respectively when compared with other fractions. Ethanol fraction was used for the in vivo study considering significant activity against ABTS. DOX-induced tissue toxicity was shown by significant (P < 0.05) hematological indices unsettling and elevated levels of serum ALT, AST, urea, LDH, CK, and MDA. Serum oxidative stress markers including SOD, CAT, and GSH were significantly (P < 0.05) reduced in DOX treated group. The leaf extract normalized hematological indices and activated levels of ALT, AST, urea, LDH, CK, and MDA due to DOX treatment. Significant elevations of SOD, CAT, and GSH were also observed following extract treatment compared to DOX exposed group. ConclusionThis study suggests that the extract potential to prevent the severity of DOX-induced toxicity may be through oxidative stress suppression.