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

被引:19
作者
Suwannakot, Kornrawee [1 ,2 ]
Sritawan, Nataya [1 ,2 ]
Naewla, Salinee [3 ]
Aranarochana, Anusara [1 ,2 ]
Sirichoat, Apiwat [1 ,2 ]
Pannangrong, Wanassanun [1 ]
Wigmore, Peter [4 ]
Welbat, Jariya Umka [1 ,2 ]
机构
[1] Khon Kaen Univ, Fac Med, Dept Anat, Khon Kaen 40002, Thailand
[2] Khon Kaen Univ, Fac Med, Dept Anat, Neurogenesis Res Grp, Khon Kaen 40002, Thailand
[3] Navamindradhiraj Univ, Fac Med Vajira Hosp, Dept Basic Med Sci, Bangkok, Thailand
[4] Univ Nottingham, Sch Life Sci, Med Sch, Queens Med Ctr, Nottingham NG72RD, Notts, England
关键词
SPATIAL MEMORY IMPAIRMENT; OXIDATIVE STRESS; CELL-PROLIFERATION; SIGNALING PATHWAY; SYNAPTIC PLASTICITY; DAMAGE; NEUROTROPHINS; ACTIVATION; EXPRESSION; APOPTOSIS;
D O I
10.1155/2022/1596362
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
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页数:13
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