Please use this identifier to cite or link to this item: http://cmuir.cmu.ac.th/jspui/handle/6653943832/55155
Title: Melatonin improves methamphetamine-induced blood brain barrier impairment through NADPH oxidase-2 in primary rat brain microvascular endothelium cells
Authors: Pichaya Jumnongprakhon
Piyarat Govitrapong
Chainarong Tocharus
Jiraporn Tocharus
Keywords: Biochemistry, Genetics and Molecular Biology
Medicine
Neuroscience
Issue Date: 1-Sep-2016
Abstract: © 2016 Elsevier B.V. Melatonin is a neurohormone and has high potent of antioxidant that is widely reported to be active against methamphetamine (METH)-induced toxicity to neuron, glial cells, and brain endothelial cells. However, the role of melatonin on the inflammatory responses which are mostly caused by blood-brain barrier (BBB) impairment by METH administration has not been investigated. This study used the primary rat brain microvascular endothelial cells (BMVECs) to determine the protective mechanism of melatonin on METH-induced inflammatory responses in the BBB via nuclear factor-KB (NF-κB) and nuclear factor erythroid 2-related factor-2 (Nrf2) signaling. Herein, we demonstrated that melatonin reduced the level of the inflammatory mediators, including intercellular adhesion molecules (ICAM)-1, vascular cell adhesion molecules (VCAM)-1, matrix metallopeptidase (MMP)-9, inducible nitric oxide synthase (iNOS), and nitric oxide (NO) caused by METH. These responses were related to the decrease of the expression and translocation of the NF-κB p65 subunit and the activity of NADPH oxidase (NOX)-2. In addition, melatonin promoted the antioxidant processes, modulated the expression and translocation of Nrf2, and also increased the level of heme oxygenase (HO)-1, NAD (P) H: quinone oxidoreductase (NQO)-1, γ-glutamylcysteine synthase (γ-GCLC), and the activity of superoxide dismutase (SOD) through NOX2 mechanism. In addition, we found that the protective role of melatonin in METH-induced inflammatory responses in the BBB was mediated through melatonin receptors (MT1/2). We concluded that the interaction of melatonin with its receptor prevented METH-induced inflammatory responses by suppressing the NF-κB signaling and promoting the Nrf2 signaling before BBB impairment.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84976612023&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/55155
ISSN: 18726240
00068993
Appears in Collections:CMUL: Journal Articles

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