Morin attenuates ifosfamide-induced neurotoxicity in rats via suppression of oxidative stress, neuroinflammation and neuronal apoptosis

Abstract

Ifosfamide (IFA), a commonly used chemotherapeutic drug, has been frequently associated with encephalopathy and central nervous system toxicity. The present study aims to investigate whether morin could protect against acute IFA-induced neurotoxicity. Morin was administered to male rats once daily for 2 consecutive days at doses of 100 and 200 mg/kg body weight (BW) orally. IFA (500 mg/kg BW; i.p.) was administered on second day. The results showed that morin markedly inhibited the production of acetylcholinesterase (AChE), butrylcholinesterase (BChE), carbonic anhydrase (CA), glial fibrillary acidic protein (GFAP), brain-derived neurotrophic factor (BDNF) and nuclear factor erythroid 2-related factor 2 (Nrf-2) induced by IFA. Morin ameliorated IFA-induced lipid peroxidation, glutathione (GSH) depletion, and decrease antioxidant enzyme activities, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx). Histopathological changes and immunohistochemical expressions of c-Jun N-terminal kinase (JNK) and c-Fos in the IFA-induced brain tissues were decreased after administration of morin. Furthermore, morin was able to down regulate the levels of inflammatory and apoptotic markers such as nuclear factor kappa B (NF-κB), neuronal nitric oxide synthase (nNOS), tumor necrosis factor-α (TNF-α), p53, cysteine aspartate specific protease-3 (caspase-3) and B-cell lymphoma-2 (Bcl-2). Taken together, our results demonstrated that morin elicited a typical chemoprotective effect on IFA-induced acute neurotoxicity. © 2019 Elsevier B.V.