Salimi_2023_Hum.Exp.Toxicol_42_9603271221147883

BACKGROUND: Ifosfamide (IFO) is a widely used antineoplastic drug with broad-spectrum efficacy against various types of cancer. However, different toxicities associated with IFO has limited its use. This study was to establish the prophylactic effects of betanin, chrysin and ellagic acid against IFO-induced neurotoxicity in rats. METHODS: Animals were randomly divided into eight groups, control, IFO, IFO + betanin, IFO + chrysin, IFO + ellagic acid, betanin, chrysin and ellagic acid groups. Betanin (50 mg/kg, i.p.), chrysin (25 mg/kg, i.p.) and ellagic acid (25 mg/kg, i.p.) were administered to rats once daily for two consecutive days. IFO (500 mg/kg, i.p.) was administered on third day. RESULTS: Results demonstrated that only ellagic acid markedly decreased the activity of acetylcholinesterase (AChE) and butrylcholinesterase (BChE) compared with IFO alone, while chrysin was only effective on BChE activity. Also, ellagic acid ameliorated IFO-induced lipid peroxidation and glutathione (GSH) depletion, while chrysin only decreased GSH depletion. Histopathological alteration in the IFO-induced brain tissues were decreased especially after administration of ellagic acid. Intraperitoneal pretreatment with betanin, followed by IFO resulted in death of all treated animals. In addition, all mitochondrial toxicity parameters induced by IFO in the rat brain tissue were ameliorated by ellagic acid, chrysin and even betanin. CONCLUSION: Taken together, our results demonstrated that especially ellagic acid and to some extent chrysin show a typical neuroprotective effect on IFO-induced acute neurotoxicity through mitochondrial protection and antioxidant properties. Also, the results of our studies showed that pretreatment with betanin followed by IFO was lethal.