Anti‐oxidant Activity Mediated Neuroprotective Potential of Trimetazidine on Focal Cerebral Ischaemia–reperfusion Injury in Rats

Dhote, Vipin; Balaraman, R

doi:10.1111/j.1440-1681.2008.04845.x

Cited by 30 publications

(19 citation statements)

References 58 publications

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“…In addition to natural extracts, studies have found that commonly used cardiovascular drugs such as simvastatin (transfusion of lipids) and trimetazidine (anti-angina drugs) have anti-CIRI effects, and that the mechanism involves anti-oxidative activity (Dhote and Balaraman, 2008;Beretta et al, 2011;Anthony Jalin et al, 2015). Lipophilic simvastatin can significantly improve the antioxidant capacity of ischemic brain tissue, while hydrophilic simvastatin has no obvious brain protection properties (Beretta et al, 2011), suggesting that increasing bloodcerebrospinal fluid barrier permeability could be an effective way to improve the treatment of CIRI with existing drugs.…”

Section: Synthetic Antioxidantmentioning

confidence: 99%

Targeting Oxidative Stress and Inflammation to Prevent Ischemia-Reperfusion Injury

Xiong

et al. 2020

Front. Mol. Neurosci.

326

197

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The cerebral ischemia injury can result in neuronal death and/or functional impairment, which leads to further damage and dysfunction after recovery of blood supply. Cerebral ischemia/reperfusion injury (CIRI) often causes irreversible brain damage and neuronal injury and death, which involves many complex pathological processes including oxidative stress, amino acid toxicity, the release of endogenous substances, inflammation and apoptosis. Oxidative stress and inflammation are interactive and play critical roles in ischemia/reperfusion injury in the brain. Oxidative stress is important in the pathological process of ischemic stroke and is critical for the cascade development of ischemic injury. Oxidative stress is caused by reactive oxygen species (ROS) during cerebral ischemia and is more likely to lead to cell death and ultimately brain death after reperfusion. During reperfusion especially, superoxide anion free radicals, hydroxyl free radicals, and nitric oxide (NO) are produced, which can cause lipid peroxidation, inflammation and cell apoptosis. Inflammation alters the balance between pro-inflammatory and anti-inflammatory factors in cerebral ischemic injury. Inflammatory factors can therefore stimulate or exacerbate inflammation and aggravate ischemic injury. Neuroprotective therapies for various stages of the cerebral ischemia cascade response have received widespread attention. At present, neuroprotective drugs mainly include free radical scavengers, anti-inflammatory agents, and anti-apoptotic agents. However, the molecular mechanisms of the interaction between oxidative stress and inflammation, and their interplay with different types of programmed cell death in ischemia/reperfusion injury are unclear. The development of a suitable method for combination therapy has become a hot topic.

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Section: Synthetic Antioxidantmentioning

confidence: 99%

Targeting Oxidative Stress and Inflammation to Prevent Ischemia-Reperfusion Injury

Xiong

et al. 2020

Front. Mol. Neurosci.

326

197

View full text Add to dashboard Cite

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“…SOD converts superoxide into oxygen and hydrogen peroxide. Similar to glutathione, many treatments that ameliorate stroke damage are accompanied by an increase in SOD [113, 114]. Furthermore, rodents overexpressing SOD1 have significantly smaller injuries after both focal and global ischemia [115, 116], while mice with decreased SOD1 have larger infarcts [117].…”

Section: Astrocyte Support Of Neurons After Strokementioning

confidence: 99%

Astrocytes: Targets for Neuroprotection in Stroke

Barreto¹,

White²,

Ouyang³

et al. 2011

CNSAMC

256

179

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In the past two decades, over 1000 clinical trials have failed to demonstrate a benefit in treating stroke, with the exception of thrombolytics. Although many targets have been pursued, including antioxidants, calcium channel blockers, glutamate receptor blockers, and neurotrophic factors, often the focus has been on neuronal mechanisms of injury. Broader attention to loss and dysfunction of non-neuronal cell types is now required to increase the chance of success. Of the several glial cell types, this review will focus on astrocytes. Astrocytes are the most abundant cell type in the higher mammalian nervous system, and they play key roles in normal CNS physiology and in central nervous system injury and pathology. In the setting of ischemia astrocytes perform multiple functions, some beneficial and some potentially detrimental, making them excellent candidates as therapeutic targets to improve outcome following stroke and in other central nervous system injuries. The older neurocentric view of the central nervous system has changed radically with the growing understanding of the many essential functions of astrocytes. These include K+ buffering, glutamate clearance, brain antioxidant defense, close metabolic coupling with neurons, and modulation of neuronal excitability. In this review, we will focus on those functions of astrocytes that can both protect and endanger neurons, and discuss how manipulating these functions provides a novel and important strategy to enhance neuronal survival and improve outcome following cerebral ischemia.

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“…Recently, some reports indicate the neuroprotective effects of trimetazidine in various experimental models. These effects have been suggested to be due to its antioxidant property (Mironovan et al 2001;Dhote and Balaraman 2008;Serarslan et al 2009). Baltalarli et al (2000) and Iqbal et al (2002) showed that administration of trimetazidine during the period of ischemia-reperfusion injury reduced the number of damaged cells in cerebral tissue and preserved neurological function in transient global ischemia model in rats and gerbils, respectively.…”

Section: Introductionmentioning

confidence: 95%

Anticonvulsant and antioxidant actions of trimetazidine in pentylenetetrazole-induced kindling model in mice

Jain

Bharal

Khurana

et al. 2011

Naunyn-Schmied Arch Pharmacol

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The present study was carried out to investigate the effect of trimetazidine on the course of pentylenetetrazole (PTZ)-induced chemical kindling and oxidative stress markers in PTZ-kindled mice. Kindling was induced by repeated injections of a subconvulsive dose of PTZ (30 mg⁄kg, i.p.) on alternate days for 5 weeks or until stage 4 of the seizure score was evoked on three consecutive administrations. Trimetazidine was administered daily in three doses (5, 10 and 20 mg/kg) per orally (p.o.) along with alternate-day PTZ. Following PTZ kindling, oxidative stress parameters, i.e. levels of malondialdehyde (MDA) and reduced glutathione (GSH), were assessed in isolated homogenized whole brain tissue. The results showed that PTZ treatment progressively increased the seizure score in control mice. Biochemical analysis revealed a significant increase in MDA levels and decreased GSH levels in the brain homogenate of PTZ-kindled mice. Daily treatment with trimetazidine in doses of 10 and 20 mg/kg significantly decreased the PTZ-induced seizure score. However, a low dose of trimetazidine (5 mg/kg) failed to improve the seizure score. Pretreatment of trimetazidine in all doses showed an ameliorating effect on biochemical alteration induced by PTZ treatment. The results of the present study indicate the potential anticonvulsant activity of trimetazidine against PTZ-induced kindling in mice.

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Anti‐oxidant Activity Mediated Neuroprotective Potential of Trimetazidine on Focal Cerebral Ischaemia–reperfusion Injury in Rats

Cited by 30 publications

References 58 publications

Targeting Oxidative Stress and Inflammation to Prevent Ischemia-Reperfusion Injury

Targeting Oxidative Stress and Inflammation to Prevent Ischemia-Reperfusion Injury

Astrocytes: Targets for Neuroprotection in Stroke

Anticonvulsant and antioxidant actions of trimetazidine in pentylenetetrazole-induced kindling model in mice

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