Tropisetron ameliorates ischemic brain injury in an embolic model of stroke

Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran.
Brain research (Impact Factor: 2.84). 03/2011; 1392:101-9. DOI: 10.1016/j.brainres.2011.03.053
Source: PubMed


Tropisetron is widely used to counteract chemotherapy-induced emesis. Evidence obtained from human and animal studies shows that tropisetron possesses anti-inflammatory properties. In this study, we assessed the effect of tropisetron on brain damage in a rat thromboembolic model of stroke. Stroke was rendered in rats by introduction of an autologous clot into the middle cerebral artery (MCA). Tropisetron (1 or 3mg/kg); m-chlorophenylbiguanide (mCPBG), a selective 5-HT(3) receptor agonist (15 mg/kg); tropisetron (3mg/kg) plus mCPBG (15 mg/kg); granisetron (3mg/kg); tacrolimus (1mg/kg); or tacrolimus (1mg/kg) plus tropisetron (3mg/kg) were administered intraperitoneally 1h prior to embolization. Behavioral scores and infarct volume as well as myeloperoxidase (MPO) activity and tumor necrosis factor-alpha (TNF-α) level were determined in the ipsilateral cortex 4h and 48 h following stroke induction. Forty-eight hours after embolization, tropisetron (1 or 3mg/kg), tropisetron (3mg/kg) plus mCPBG (15 mg/kg), tacrolimus (1mg/kg), or tacrolimus (1mg/kg) plus tropisetron (3mg/kg) significantly curtailed brain infarction, improved behavioral scores, diminished elevated tissue MPO activity, and reduced TNF-α levels compared to control group (n=6; P<0.05). mCPBG or granisetron had no effect on the mentioned parameters. Tropisetron attenuates brain damage after a thromboembolic event. Beneficial effects of tropisetron in this setting are receptor independent.

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Available from: Reza Rahimian
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    • "In this context, we showed that tropisetron is able to attenuate O&NS as well as inflammatory responses in animal models of Alzheimer's disease and stroke [26] [27]. In addition, recent studies have reported the antidepressant-like properties of 5-HT3 antagonists (including tropisetron) in both non-stressed and stressed animals [28] [29] [30]. "
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    ABSTRACT: Background: Early social isolation stress (SIS) is associated with the occurrence of anxiety behaviors. It seems interaction between the nitrergic system and mitochondrial function plays a role in mediating the anxiety-like behaviors. In this study, we aimed to investigate the anxiolytic effects of tropisetron in animal model of SIS and we try to illustrate the possible role of nitrergic system and mitochondrial function. Methods: We applied early social isolation paradigm to male NMRI mice. Animals treated with various doses of tropisetron, nitric oxide agents or their combination and anxiety-like behaviors of animals were assessed using valid behavioral tests including elevated plus maze (EPM), open-field test (OFT) and hole-board test (HBT) in their adulthood. Effects of housing conditions and drug treatments on the mitochondrial function were investigated in the hippocampus by assessing the ATP, GSH, ROS and nitrite levels. Results: anxiogenic effects of early SIS were assessed in the EPM, OFT, and HBT. Also, SIS disrupted mitochondrial function and caused oxidative stress in the hippocampus of stressed animals. Tropisetron showed an anxiolytic effect in the stressed mice. Also, these effects were mediated by nitrergic system by affecting mitochondrial function and modulating the oxidative stress. L-arginine, a nitric oxide precursor, abolished the anxiolytic effects of tropisetron in the behavioral tasks and blocked the protective effects of it against mitochondrial and oxidative challenge. Conclusions and general significance: Our results demonstrated tropisetron attenuated the anxiogenic effects of SIS by mitigation of the negative effects of nitric oxide on mitochondrial function.
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    • "20 (TBST) and 2% skim milk for 1.15 h. The PVDF was then incubated overnight at 4 °C with anti-iNOS enzyme (Rahimian et al., 2011). "
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    • "20 (TBST) and 2% skim milk for 1.15 h. The PVDF was then incubated overnight at 4 °C with anti-iNOS enzyme (Rahimian et al., 2011). "

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