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  • Title: Thromboxane A2 synthase inhibition ameliorates endothelial dysfunction, memory deficits, oxidative stress and neuroinflammation in rat model of streptozotocin diabetes induced dementia.
    Author: Bhatia P, Singh N.
    Journal: Physiol Behav; 2021 Nov 01; 241():113592. PubMed ID: 34534530.
    Abstract:
    RATIONALE: Vascular dementia (VaD) is the second leading cause of dementia worldwide. It is very important to find the possible pharmacological agents which may be useful in management and therapy of VaD. OBJECTIVES: The present study investigates the effect of ozagrel, a selective thromboxane A2 (TXA2) synthase inhibitor, in a rat model of VaD. METHODS: Single intraperitoneal injection of streptozotocin [STZ, (50 mg/kg)] was administered to Wistar rats to induced diabetes-associated vascular endothelial dysfunction and memory impairment. Morris water maze (MWM) test was employed to assess learning and memory. Endothelial dysfunction was assessed in the isolated aorta by observing endothelial-dependent vasorelaxation and levels of serum nitrite. Various biochemical and histopathological estimations were also performed. RESULTS: STZ treatment produced endothelial dysfunction, impairment of learning and memory, reduction in body weight and serum nitrite/nitrate, and increase in serum glucose, brain oxidative stress (increased brain thiobarbituric acid reactive species and decreased reduced glutathione levels), brain acetylcholinesterase activity and brain myeloperoxidase activity. Further a significant rise in brain tumor necrosis factor-α & interleukin-6 levels and brain neutrophil infiltration were also observed. Treatment of ozagrel (10 & 20 mg/kg, p. o.)/donepezil (0. 5 mg/kg, i.p., serving as standard) ameliorated STZ induced endothelial dysfunction; memory deficits; biochemical and histopathological changes. CONCLUSIONS: It may be concluded that ozagrel markedly improved endothelial dysfunction; learning and memory; biochemical and histopathological alteration associated with STZ induced dementia and that TXA2 can be considered as an important therapeutic target for the management of VaD.
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