Melatonin Protects against the Side-Effects of 5-Fluorouracil on Hippocampal Neurogenesis and Ameliorates Antioxidant Activity in an Adult Rat Hippocampus and Prefrontal Cortex
Melatonin is an endogenous hormone that exhibits antioxidant functions and neuroprotective effects. The hippocampus and the prefrontal cortex (PFC) play an important role linked to working memory. 5-fluorouracil (5-FU) can induce oxidative stress and reduce neurogenesis in the subgranular zone (SGZ)...
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MDPI AG
2021-04-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/4/615 |
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| author | Kornrawee Suwannakot Nataya Sritawan Ram Prajit Anusara Aranarochana Apiwat Sirichoat Wanassanun Pannangrong Peter Wigmore Jariya Umka Welbat |
| author_facet | Kornrawee Suwannakot Nataya Sritawan Ram Prajit Anusara Aranarochana Apiwat Sirichoat Wanassanun Pannangrong Peter Wigmore Jariya Umka Welbat |
| author_sort | Kornrawee Suwannakot |
| collection | DOAJ |
| description | Melatonin is an endogenous hormone that exhibits antioxidant functions and neuroprotective effects. The hippocampus and the prefrontal cortex (PFC) play an important role linked to working memory. 5-fluorouracil (5-FU) can induce oxidative stress and reduce neurogenesis in the subgranular zone (SGZ) of the dentate gyrus in a rat hippocampus and these alterations are related to working memory deficits. This study aimed to determine the effect of melatonin on 5-FU-induced oxidative stress that interferes with the antioxidant enzymes and protein expression levels in a rat hippocampus and PFC. A total of 68 male Sprague Dawley rats were divided into four groups: vehicle, 5-FU, melatonin and melatonin+5-FU groups. Rats were administered 5-FU (25 mg/kg, i.v.) on days 9, 12, 15, 18 and 21 and received melatonin (8 mg/kg, i.p.) at 19:00 from day 1 to day 21 of the experiment. Lipid peroxidation was assessed by measuring malondialdehyde (MDA) levels. Antioxidant enzyme levels including glutathione peroxidase (GPX), catalase (CAT) and superoxide dismutase (SOD) were determined. p21 immunofluorescence staining and Western blotting were used to detect the cell cycle arrest and protein expression of the nuclear factor erythroid 2-related factor 2 (Nrf2), doublecortin (DCX) and brain derived neurotrophic factor (BDNF), respectively. The results showed that melatonin reduced the number of p21-positive cells in the SGZ of the dentate gyrus and increased Nrf2, DCX and BDNF protein expression in rats treated with 5-FU. Moreover, melatonin restored antioxidant enzyme levels and reduced oxidative stress in the hippocampus and PFC caused by 5-FU. These findings reveal a mechanism of the neuroprotective properties of melatonin against 5-FU in a rat hippocampus and PFC. |
| first_indexed | 2024-03-10T12:15:38Z |
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| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T12:15:38Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-af1093f4937344cc8f3112093421fcb82023-11-21T15:53:50ZengMDPI AGAntioxidants2076-39212021-04-0110461510.3390/antiox10040615Melatonin Protects against the Side-Effects of 5-Fluorouracil on Hippocampal Neurogenesis and Ameliorates Antioxidant Activity in an Adult Rat Hippocampus and Prefrontal CortexKornrawee Suwannakot0Nataya Sritawan1Ram Prajit2Anusara Aranarochana3Apiwat Sirichoat4Wanassanun Pannangrong5Peter Wigmore6Jariya Umka Welbat7Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, ThailandDepartment of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, ThailandDepartment of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, ThailandDepartment of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, ThailandDepartment of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, ThailandDepartment of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, ThailandQueen’s Medical Centre, School of Life Sciences, Medical School, University of Nottingham, Nottingham NG7 2RD, UKDepartment of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, ThailandMelatonin is an endogenous hormone that exhibits antioxidant functions and neuroprotective effects. The hippocampus and the prefrontal cortex (PFC) play an important role linked to working memory. 5-fluorouracil (5-FU) can induce oxidative stress and reduce neurogenesis in the subgranular zone (SGZ) of the dentate gyrus in a rat hippocampus and these alterations are related to working memory deficits. This study aimed to determine the effect of melatonin on 5-FU-induced oxidative stress that interferes with the antioxidant enzymes and protein expression levels in a rat hippocampus and PFC. A total of 68 male Sprague Dawley rats were divided into four groups: vehicle, 5-FU, melatonin and melatonin+5-FU groups. Rats were administered 5-FU (25 mg/kg, i.v.) on days 9, 12, 15, 18 and 21 and received melatonin (8 mg/kg, i.p.) at 19:00 from day 1 to day 21 of the experiment. Lipid peroxidation was assessed by measuring malondialdehyde (MDA) levels. Antioxidant enzyme levels including glutathione peroxidase (GPX), catalase (CAT) and superoxide dismutase (SOD) were determined. p21 immunofluorescence staining and Western blotting were used to detect the cell cycle arrest and protein expression of the nuclear factor erythroid 2-related factor 2 (Nrf2), doublecortin (DCX) and brain derived neurotrophic factor (BDNF), respectively. The results showed that melatonin reduced the number of p21-positive cells in the SGZ of the dentate gyrus and increased Nrf2, DCX and BDNF protein expression in rats treated with 5-FU. Moreover, melatonin restored antioxidant enzyme levels and reduced oxidative stress in the hippocampus and PFC caused by 5-FU. These findings reveal a mechanism of the neuroprotective properties of melatonin against 5-FU in a rat hippocampus and PFC.https://www.mdpi.com/2076-3921/10/4/615melatonin5-fluorouracilhippocampusprefrontal cortexneurogenesisantioxidant enzymes |
| spellingShingle | Kornrawee Suwannakot Nataya Sritawan Ram Prajit Anusara Aranarochana Apiwat Sirichoat Wanassanun Pannangrong Peter Wigmore Jariya Umka Welbat Melatonin Protects against the Side-Effects of 5-Fluorouracil on Hippocampal Neurogenesis and Ameliorates Antioxidant Activity in an Adult Rat Hippocampus and Prefrontal Cortex Antioxidants melatonin 5-fluorouracil hippocampus prefrontal cortex neurogenesis antioxidant enzymes |
| title | Melatonin Protects against the Side-Effects of 5-Fluorouracil on Hippocampal Neurogenesis and Ameliorates Antioxidant Activity in an Adult Rat Hippocampus and Prefrontal Cortex |
| title_full | Melatonin Protects against the Side-Effects of 5-Fluorouracil on Hippocampal Neurogenesis and Ameliorates Antioxidant Activity in an Adult Rat Hippocampus and Prefrontal Cortex |
| title_fullStr | Melatonin Protects against the Side-Effects of 5-Fluorouracil on Hippocampal Neurogenesis and Ameliorates Antioxidant Activity in an Adult Rat Hippocampus and Prefrontal Cortex |
| title_full_unstemmed | Melatonin Protects against the Side-Effects of 5-Fluorouracil on Hippocampal Neurogenesis and Ameliorates Antioxidant Activity in an Adult Rat Hippocampus and Prefrontal Cortex |
| title_short | Melatonin Protects against the Side-Effects of 5-Fluorouracil on Hippocampal Neurogenesis and Ameliorates Antioxidant Activity in an Adult Rat Hippocampus and Prefrontal Cortex |
| title_sort | melatonin protects against the side effects of 5 fluorouracil on hippocampal neurogenesis and ameliorates antioxidant activity in an adult rat hippocampus and prefrontal cortex |
| topic | melatonin 5-fluorouracil hippocampus prefrontal cortex neurogenesis antioxidant enzymes |
| url | https://www.mdpi.com/2076-3921/10/4/615 |
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