Amifostine ameliorates cerebral ischaemia-reperfusion injury via p38-mediated oxidative stress and mitochondrial dysfunction

Amifostine is a cytoprotective compound that is beneficial in ischaemic stroke cases. However, the neuroprotective effect of amifostine on ischaemia/reperfusion (I/R)-induced brain injury and its underlying mechanism are still poorly understood. Herein, we constructed an animal model of middle cereb...

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Main Authors: Huifeng Cheng, Miaojun Lv, Rulin Mi, Guofang Xue
Format: Article
Language:English
Published: Termedia Publishing House 2021-01-01
Series:Folia Neuropathologica
Subjects:
Online Access:https://www.termedia.pl/Amifostine-ameliorates-cerebral-ischaemia-reperfusion-injury-r-nvia-p38-mediated-oxidative-stress-and-mitochondrial-dysfunction,20,42964,1,1.html
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spelling doaj-7d4f514118e84426923f44a3552a56f02021-10-06T10:22:37ZengTermedia Publishing HouseFolia Neuropathologica1641-46401509-572X2021-01-0158433434610.5114/fn.2020.10243642964Amifostine ameliorates cerebral ischaemia-reperfusion injury via p38-mediated oxidative stress and mitochondrial dysfunctionHuifeng ChengMiaojun LvRulin MiGuofang XueAmifostine is a cytoprotective compound that is beneficial in ischaemic stroke cases. However, the neuroprotective effect of amifostine on ischaemia/reperfusion (I/R)-induced brain injury and its underlying mechanism are still poorly understood. Herein, we constructed an animal model of middle cerebral artery occlusion and reperfusion (MCAO/R) injury and an in vitro model of oxygen and glucose deprivation and reperfusion (OGD/R) injury. After administration of amifostine, we found significant improvements in neurological deficits, infarct size, and cerebral oedema. Moreover, amifostine alleviated histopathological alteration and increased the number of surviving neurons. Biochemical analysis showed that treatment with amifostine obviously improved the brain damage of MCAO/R mice, as manifested by a decrease in reactive oxygen species (ROS) and malondialdehyde (MDA) generation, and an increase in superoxide dismutase (SOD) activity. Moreover, amifostine decreased the mitochondrial membrane potential (m) loss, and cytochrome c escaping to cytoplasm, but increased the ATP level. In vitro, amifostine also showed an antioxidant effect, which was reflected by the reduced ROS generation, decreased mitochondrial superoxide generation, increased total SOD, SOD1 (Cu/Zn SOD, cytoplasmic SOD), and SOD2 (mitochondrial SOD) activities, and decreased m loss. Furthermore, amifostine suppressed neuronal apoptosis, accompanied by the reduction of Bax, cleaved caspase-9, cleaved caspase-3, and Bcl-2 upregulation. Amifostine also reduced the expression of p-p38 (Thr 180/Tyr 182) in vivo and in vitro. In short, amifostine exhibits a protective effect on cerebral I/R damage through modulating p38-related oxidative stress, mitochondrial dysfunction, and apoptosis.https://www.termedia.pl/Amifostine-ameliorates-cerebral-ischaemia-reperfusion-injury-r-nvia-p38-mediated-oxidative-stress-and-mitochondrial-dysfunction,20,42964,1,1.htmlamifostine ischaemia-reperfusion injury brain mitochondrial dysfunction neuron.
collection DOAJ
language English
format Article
sources DOAJ
author Huifeng Cheng
Miaojun Lv
Rulin Mi
Guofang Xue
spellingShingle Huifeng Cheng
Miaojun Lv
Rulin Mi
Guofang Xue
Amifostine ameliorates cerebral ischaemia-reperfusion injury via p38-mediated oxidative stress and mitochondrial dysfunction
Folia Neuropathologica
amifostine
ischaemia-reperfusion injury
brain
mitochondrial dysfunction
neuron.
author_facet Huifeng Cheng
Miaojun Lv
Rulin Mi
Guofang Xue
author_sort Huifeng Cheng
title Amifostine ameliorates cerebral ischaemia-reperfusion injury via p38-mediated oxidative stress and mitochondrial dysfunction
title_short Amifostine ameliorates cerebral ischaemia-reperfusion injury via p38-mediated oxidative stress and mitochondrial dysfunction
title_full Amifostine ameliorates cerebral ischaemia-reperfusion injury via p38-mediated oxidative stress and mitochondrial dysfunction
title_fullStr Amifostine ameliorates cerebral ischaemia-reperfusion injury via p38-mediated oxidative stress and mitochondrial dysfunction
title_full_unstemmed Amifostine ameliorates cerebral ischaemia-reperfusion injury via p38-mediated oxidative stress and mitochondrial dysfunction
title_sort amifostine ameliorates cerebral ischaemia-reperfusion injury via p38-mediated oxidative stress and mitochondrial dysfunction
publisher Termedia Publishing House
series Folia Neuropathologica
issn 1641-4640
1509-572X
publishDate 2021-01-01
description Amifostine is a cytoprotective compound that is beneficial in ischaemic stroke cases. However, the neuroprotective effect of amifostine on ischaemia/reperfusion (I/R)-induced brain injury and its underlying mechanism are still poorly understood. Herein, we constructed an animal model of middle cerebral artery occlusion and reperfusion (MCAO/R) injury and an in vitro model of oxygen and glucose deprivation and reperfusion (OGD/R) injury. After administration of amifostine, we found significant improvements in neurological deficits, infarct size, and cerebral oedema. Moreover, amifostine alleviated histopathological alteration and increased the number of surviving neurons. Biochemical analysis showed that treatment with amifostine obviously improved the brain damage of MCAO/R mice, as manifested by a decrease in reactive oxygen species (ROS) and malondialdehyde (MDA) generation, and an increase in superoxide dismutase (SOD) activity. Moreover, amifostine decreased the mitochondrial membrane potential (m) loss, and cytochrome c escaping to cytoplasm, but increased the ATP level. In vitro, amifostine also showed an antioxidant effect, which was reflected by the reduced ROS generation, decreased mitochondrial superoxide generation, increased total SOD, SOD1 (Cu/Zn SOD, cytoplasmic SOD), and SOD2 (mitochondrial SOD) activities, and decreased m loss. Furthermore, amifostine suppressed neuronal apoptosis, accompanied by the reduction of Bax, cleaved caspase-9, cleaved caspase-3, and Bcl-2 upregulation. Amifostine also reduced the expression of p-p38 (Thr 180/Tyr 182) in vivo and in vitro. In short, amifostine exhibits a protective effect on cerebral I/R damage through modulating p38-related oxidative stress, mitochondrial dysfunction, and apoptosis.
topic amifostine
ischaemia-reperfusion injury
brain
mitochondrial dysfunction
neuron.
url https://www.termedia.pl/Amifostine-ameliorates-cerebral-ischaemia-reperfusion-injury-r-nvia-p38-mediated-oxidative-stress-and-mitochondrial-dysfunction,20,42964,1,1.html
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