Gender-related Histological Changes in the Thymus Gland After Pinealectomy and Short-term Melatonin Treatment in Rats

Susko, Irfan; Aličelebić, Selma; Ćosović, Esad; Šahinović, Maida; Kapić, Dina; Custovic, Samra; Muzika, Visnja

doi:10.5455/medarh.2017.71.385-390

Cited by 7 publications

(3 citation statements)

References 23 publications

(27 reference statements)

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“…Melatonin (Sigma-Aldrich, St. Louis, MO, USA) was immediately dissolved in 10% ethanol solution (RCI Labscan, Bangkok, Thailand) and kept in a falcon tube wrapped with aluminum foil to prevent light-induced melatonin deterioration. 10% ethanol solution was chosen according to previous studies without any toxicity [33,37,38]. MTX and leucovorin (LCV) were purchased from Pharmachemie B.V., Haarlem, Netherlands.…”

Section: Methodsmentioning

confidence: 99%

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

Suwannakot

Sritawan

Naewla

et al. 2022

Oxidative Medicine and Cellular Longevity

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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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Section: Methodsmentioning

confidence: 99%

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

Suwannakot

Sritawan

Naewla

et al. 2022

Oxidative Medicine and Cellular Longevity

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show abstract

“…Melatonin (8 mg/kg) was dissolved in 10% ethanol (RCI Labscan, Bangkok, Thailand) just before administration. Ethanol (10%) has been used to dissolve melatonin without any toxicity as described in several studies [ 7 , 11 , 32 , 33 ]. Animals were randomly assigned into four groups: vehicle, 5-FU, melatonin and melatonin+5-FU.…”

Section: Methodsmentioning

confidence: 99%

Melatonin Protects against the Side-Effects of 5-Fluorouracil on Hippocampal Neurogenesis and Ameliorates Antioxidant Activity in an Adult Rat Hippocampus and Prefrontal Cortex

et al. 2021

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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.

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“…Why did we study this particular question? In animals sex-related histological differences in the thymus after ectopic pineal gland was established [9].…”

Section: Resultsmentioning

confidence: 99%

Sex-Related Differences in the Levels of Urine 6-Sulfatoxymelatonin in Very Low Birth Weight Infants

Kuzienkova

2022

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Background. The sex-related differences of the urinary 6-sulfatoxymelatonin have not been studied in premature infants yet. The purpose of the work was to measure the daily urinary 6-sulfatoxymelatonin in premature infants with a very low birth weight. Materials and Methods. Fifty premature infants (28 males and 22 females) with gestational age less than 33 weeks and body weight from 999 g to 1499 g were involved in the study. Urine 6-sulfatoxymelatonin was assessed using urine collection on the 1st day and on the 10th‒14th days of life. Results. The level of urine 6-sulfatoxymelatonin on the 1st day of life showed a significant increase in its excretion in females compared to males. The median values in males were 202.0 (95% CI 77.1–390.9) pg/ml and in females 437.0 (279.6–501.0) pg/ml, p=0.0103. Its level on the 10th–14th days of life significantly decreased both in males 57.0 (95 % СІ 45,0–99.7) pg/ml, p=0.0028 and in females 90.0 (51.9–160.7) pg/ml, p=0.0021 without differences in sex-related distribution, p=0.3940. Conclusions. The melatonin metabolite as urinary 6-sulfatoxymelatonin in premature infants with a very low birth weight demonstrates sex-related differences with significant increase in females compared to males on the 1st day of life and no sex-related difference on the 10th–14th days of life. The trend of reduced pineal function is a key point in understanding the neuroendocrine reactivity in male preterms. Future investigation of sex-related aspects of urinary 6-sulfatoxymelatonin excretion in children, especially premature infants, is required.

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Gender-related Histological Changes in the Thymus Gland After Pinealectomy and Short-term Melatonin Treatment in Rats

Cited by 7 publications

References 23 publications

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

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

Melatonin Protects against the Side-Effects of 5-Fluorouracil on Hippocampal Neurogenesis and Ameliorates Antioxidant Activity in an Adult Rat Hippocampus and Prefrontal Cortex

Sex-Related Differences in the Levels of Urine 6-Sulfatoxymelatonin in Very Low Birth Weight Infants

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