Naringin ameliorates 5-fluorouracil elicited neurotoxicity by curtailing oxidative stress and iNOS/NF-ĸB/caspase-3 pathway

Abstract

This study evaluated the protective effects of naringin (NRG) against 5-fluorouracil (5-FU)-elicited neurotoxicity. The animals were orally administered with NRG and subsequently injected with 5-FU. Injection of 5-FU caused depression in cerebral antioxidant enzymes, including glutathione peroxidase, superoxide dismutase, catalase, reduced glutathione and total protein levels, whereas malondialdehyde and acetylcholinesterase levels/activities were considerably upregulated. In addition, 5-FU-triggered cerebral pro-inflammation was shown via significantly increased levels of pro-inflammatory cytokines, inducible nitric oxide synthase, nuclear factor-ĸB, and caspase-3. Furthermore, necrotic and inflammatory histopathological lesions were observed in the cerebral tissues. Interestingly, the NRG administration considerably inhibited 5-FU-instigated cerebral oxido-inflammatory and apoptotic parameters in the treated animals. Thus, NRG could mitigate the neurotoxicity of 5-FU via the inhibition of oxido-inflammation and apoptosis in rats. These results suggested that NRG may have a relevant therapeutic importance in the management of 5-FU-elicited neurotoxicity.

Keywords

• oxidative stress
• naringin
• 5-fluorouracil
• cancer
• apoptosis
• inflammation