Melatonin Attenuates Methotrexate-Induced Reduction of Antioxidant Activity Related to Decreases of Neurogenesis in Adult Rat Hippocampus and Prefrontal Cortex.

Autor: Suwannakot K; Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.; Neurogenesis Research Group, Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand., Sritawan N; Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.; Neurogenesis Research Group, Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand., Naewla S; Department of Basic Medical Science, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand., Aranarochana A; Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.; Neurogenesis Research Group, Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand., Sirichoat A; Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.; Neurogenesis Research Group, Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand., Pannangrong W; Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand., Wigmore P; School of Life Sciences, Medical School, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2RD, UK., Welbat JU; Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.; Neurogenesis Research Group, Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
Jazyk: angličtina
Zdroj: Oxidative medicine and cellular longevity [Oxid Med Cell Longev] 2022 Jul 15; Vol. 2022, pp. 1596362. Date of Electronic Publication: 2022 Jul 15 (Print Publication: 2022).
DOI: 10.1155/2022/1596362
Abstrakt: Previous studies have revealed that the side effects of anticancer drugs induce a decrease of neurogenesis. Methotrexate (MTX), one of anticancer drugs, can induce lipid peroxidation as an indicator of oxidative stress in the brain. Melatonin has been presented as an antioxidant that can prevent oxidative stress-induced neuronal damage via the activation of antioxidant enzymes associated with the increase of neurogenesis. The aims of the present study are to examine the neuroprotective effect of melatonin on the neurotoxicity of MTX on neurogenesis and the changes of protein expression and antioxidant enzyme levels in adult rat hippocampus and prefrontal cortex (PFC). Male Sprague-Dawley rats were assigned into four groups: vehicle, MTX, melatonin, and melatonin+MTX groups. The vehicle group received saline solution and 10% ethanol solution, whereas the experimental groups received MTX (75 mg/kg, i.v.) and melatonin (8 mg/kg, i.p.) treatments. After the animal examination, the brains were removed for p21 immunofluorescence staining. The hippocampus and PFC were harvested for Western blot analysis and biochemical assessments of malondialdehyde (MDA), catalase (CAT), glutathione peroxidase (GPX), and superoxide dismutase (SOD). The immunofluorescence result showed that coadministration with melatonin diminished p21-positive cells in the hippocampal dentate gyrus, indicating a decrease of cell cycle arrest. Melatonin reduced the levels of MDA and prevented the decline of antioxidant enzyme activities in rats receiving MTX. In the melatonin+MTX group, the protein expression results showed that melatonin treatment significantly upregulated synaptic plasticity and an immature neuron marker through enhancing brain derived neurotrophic factor (BDNF) and doublecortin (DCX), respectively. Moreover, melatonin ameliorated the antioxidant defense system by improving the nuclear factor erythroid 2-related factor 2 (Nrf2) in rats receiving MTX. These findings suggested that the effects of melatonin can ameliorate MTX toxicity by several mechanisms, including an increase of endogenous antioxidants and neurogenesis in adult rat hippocampus and PFC.
Competing Interests: The authors declare no conflict of interests.
(Copyright © 2022 Kornrawee Suwannakot et al.)
Databáze: MEDLINE
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