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Background and objectives: Methotrexate is a chemotherapy drug used to treat many different cancers. Several studies have reported that methotrexate has neurotoxic effects, leading to memory impairments. Hesperidin is a natural compound which exhibits anti-inflammatory and antioxidant properties. Furthermore, hesperidin enhances learning and memory. Therefore, the aim of this study was to investigate the effect of hesperidin on memory impairment caused by methotrexate.
Methods: Twenty-four male Sprague Dawley rats (age: 4-5 weeks) were divided into 4 groups (6 animals/group). Vehicle group received saline and propylene glycol. Hesperidin group received hesperidin only. Finally, methotrexate group received only methotrexate and methotrexate+hesperidin group received both methotrexate and hesperidin. A single dose of methotrexate (75 mg/kg) was administered by intravenous injection on day 8 and 15. Hesperidin (100 mg/kg) was administered per oral for 21 days. Three days after the end of drug administration, memory was tested using the novel object location and novel object recognition.
Results: The results showed that total exploration time was not significantly different among groups in both novel object location and novel object recognition tests (p>0.05). In novel object location test, rats in vehicle, hesperidin and methotrexate+hesperidin groups could significantly discriminate between the objects placed in the novel and familiar locations (p< 0.05). Similar, in the novel object recognition test, rats in vehicle, hesperidin and methotrexate+hesperidin groups could significantly discriminate between the novel and familiar objects, whereas rats in methotrexate group did not discriminate between the novel and familiar objects (p<0.05).
Conclusion: The results of this experiment indicated that hesperidin is able to prevent and improve the memory impairments induced by methotrexate in adult rats.
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