Trial for decreasing ifosfamide-induced hematological toxicity, oxidative stress, inflammation, and hepatotoxicity by beetroot extract in male albino rats

Hepatotoxicity restricts the therapeutic benefit of many anti-tumor agents in clinic. Ifosfamide is a widely used antineoplastic drug which could cause toxicity of normal cells due to its toxic metabolites mainly via induction of oxidative stress. Regarding established antioxidant and anti-inflammatory potential of beetroot extract, we aimed to investigate its possible protective effect against ifosfamide-induced hepatotoxicity in the rat model through hematological, histopathological, biochemical, and immunohistochemical evaluation of oxidative and inflammatory biomarkers. A total of twenty-four male albino rats were divided into four groups: Group 1: served as control (Cont); Group II: beetroot extract (BRE); Group III: ifosfamide only (IFOS); Group IV: ifosfamide + beetroot extract (IFOS + BRE). Results of the present study revealed that ifosfamide administration caused hematological toxicity and liver injury evidenced by elevated serum ALT, AST, and ALP and decreased TP, and marked elevation of liver MDA and NO levels with depletion of GSH and reduction of SOD and CAT activities along with several deleterious histopathological and immunohistochemical alterations in liver tissue compared to control rats. Our findings suggest that co-treatment with BRE has showed considerable protection but not full protection against ifosfamide-induced toxicity and all markers showed a regression trend towards control values. The mechanism of this protection seems to be partially based on antioxidant and anti-inflammatory properties. Therefore, it is recommended to use beetroot extract as dietary natural supplement in the clinic to approve its benefit in patients undertaking ifosfamide therapy to minimize its toxicity. © 2022, The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.