Dose-Dependent Protective Effects of Persea americana Mill. Seed Extract Against Doxorubicin Induced Multi-Organ Toxicity in Rats

Abstract

The most popular chemotherapeutic agent, Doxorubicin (DOX), is restricted by the dose-related multi-organ toxicity which is mediated mainly by oxidative stress and damage of cells. The paper assessed the dose-effective protective action of Persea americana ethanolic seed extract on the toxicity of DOX on Wistar rats. Forty two rats were randomly selected into six groups, namely, normal control, DOX control (5 mg/kg), DOX + Vitamin C (100 mg/kg), and DOX + P. americana extract at 500, 1000 and 1500 mg/kg. The treatments were given after four weeks. Standard methods were used to measure hematological parameters, indices of liver and renal functions, lipid profile, antioxidants enzyme activities, and cardiac biomarkers. The use of DOX led to a serious decrease in the number of RBC, hemoglobin, PCV, and platelets, and the simultaneous increase in the level of WBC (P < 0.05). Hepatic dysfunction was supported by high levels of AST, ALT, ALP, and bilirubin and low indices of protein levels whereas renal dysfunction was supported by high levels of urea, creatinine, and uric acid. DOX also caused dyslipidemia, lipid peroxidation (MDA), drop in antioxidant enzyme (GSH, SOD, CAT, GPx) and cardiac biomarker increase (LDH, CK-MB, troponin). Dose-dependently acute effects of P. americana extract had a significant effect in reducing these changes with the highest dose (1500 mg/kg) showing the highest inhibitory effect, which is similar to Vitamin C. The acute toxicity analysis showed no mortality up to 5000 mg/kg. Conclusively, Persea americana seed extract provides serious multi-organ coverage against DOX-induced toxicity, mainly due to the antioxidant and cytoprotective effects, which demonstrates its potential in the safe use as an adjunct in chemotherapy.