Ameliorative effect of ozagrel, a thromboxane A2 synthase inhibitor, in hyperhomocysteinemia-induced experimental vascular cognitive impairment and dementia
© 2020 Société Française de Pharmacologie et de Thérapeutique..
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 vom: 06. Aug., Seite 650-666 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bhatia, Pankaj [VerfasserIn] |
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| Links: |
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| Themen: |
57576-52-0 |
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| Anmerkungen: |
Date Completed 20.12.2021 Date Revised 20.12.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/fcp.12610 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM315911506 |
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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 © 2020 Société Française de Pharmacologie et de Thérapeutique. | ||
| 520 | |a 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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