Ameliorative effect of ozagrel, a thromboxane A2 synthase inhibitor, in hyperhomocysteinemia‐induced experimental vascular cognitive impairment and dementia
Abstract The present study investigates the effect of ozagrel, a selective thromboxane A2 (TXA2) inhibitor, in rat model of hyperhomocysteinemia (HHcy)‐induced vascular cognitive impairment and dementia (VCID). Wistar rats were administered L‐methionine (1.7 g/kg/day; p.o. × 8 weeks) to induce VCID. 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. L‐methionine produced significant impairment in endothelium‐dependent vasorelaxation and decreases serum nitrite levels indicating endothelial dysfunction. Further, these animals performed poorly on MWM, depicting impairment of learning and memory. Further, a significant rise in brain oxidative stress level (indicated by increase in brain thiobarbituric acid‐reactive species and decrease in reduced glutathione levels), brain acetylcholinesterase activity, brain myeloperoxidase activity, brain TNF‐α and IL‐6 levels, and brain leukocyte (neutrophil) infiltration was also observed. Treatment of ozagrel (10 and 20 mg/kg, p. o.)/donepezil (0.5 mg/kg, i.p., serving as standard) ameliorated L‐methionine‐induced endothelial dysfunction, memory deficits, and biochemical and histopathological changes. It may be concluded that ozagrel markedly improved endothelial dysfunction, learning and memory, and biochemical and histopathological alteration associated with L‐methionine‐induced VCID and that TXA2 can be considered as an important therapeutic target for the management of VCID..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:35 |
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| Enthalten in: |
Fundamental & Clinical Pharmacology - 35(2021), 4, Seite 650-666 |
| Beteiligte Personen: |
Bhatia, Pankaj [VerfasserIn] |
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| BKL: |
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| Anmerkungen: |
© 2021 John Wiley & Sons, Ltd. |
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| Umfang: |
17 |
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| doi: |
10.1111/fcp.12610 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Ameliorative effect of ozagrel, a thromboxane A2 synthase inhibitor, in hyperhomocysteinemia‐induced experimental vascular cognitive impairment and dementia |
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| 520 | |a Abstract The present study investigates the effect of ozagrel, a selective thromboxane A2 (TXA2) inhibitor, in rat model of hyperhomocysteinemia (HHcy)‐induced vascular cognitive impairment and dementia (VCID). Wistar rats were administered L‐methionine (1.7 g/kg/day; p.o. × 8 weeks) to induce VCID. 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. L‐methionine produced significant impairment in endothelium‐dependent vasorelaxation and decreases serum nitrite levels indicating endothelial dysfunction. Further, these animals performed poorly on MWM, depicting impairment of learning and memory. Further, a significant rise in brain oxidative stress level (indicated by increase in brain thiobarbituric acid‐reactive species and decrease in reduced glutathione levels), brain acetylcholinesterase activity, brain myeloperoxidase activity, brain TNF‐α and IL‐6 levels, and brain leukocyte (neutrophil) infiltration was also observed. Treatment of ozagrel (10 and 20 mg/kg, p. o.)/donepezil (0.5 mg/kg, i.p., serving as standard) ameliorated L‐methionine‐induced endothelial dysfunction, memory deficits, and biochemical and histopathological changes. It may be concluded that ozagrel markedly improved endothelial dysfunction, learning and memory, and biochemical and histopathological alteration associated with L‐methionine‐induced VCID and that TXA2 can be considered as an important therapeutic target for the management of VCID. | ||
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