PMID- 33020931
OWN - NLM
STAT- MEDLINE
DCOM- 20211220
LR  - 20211220
IS  - 1472-8206 (Electronic)
IS  - 0767-3981 (Linking)
VI  - 35
IP  - 4
DP  - 2021 Aug
TI  - Ameliorative effect of ozagrel, a thromboxane A2 synthase inhibitor, in 
      hyperhomocysteinemia-induced experimental vascular cognitive impairment and 
      dementia.
PG  - 650-666
LID - 10.1111/fcp.12610 [doi]
AB  - 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. x 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-alpha 
      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.
CI  - (c) 2020 Societe Francaise de Pharmacologie et de Therapeutique.
FAU - Bhatia, Pankaj
AU  - Bhatia P
AD  - CNS Research Lab., Pharmacology Division, Department of Pharmaceutical Sciences 
      and Drug Research, Faculty of Medicine, Punjabi University, Patiala, Punjab, 
      147002, India.
FAU - Singh, Nirmal
AU  - Singh N
AUID- ORCID: 0000-0001-6143-5284
AD  - Pharmacology Division, Department of Pharmaceutical Sciences and Drug Research, 
      Faculty of Medicine, Punjabi University, Patiala, Punjab, 147002, India.
LA  - eng
PT  - Journal Article
DEP - 20201205
PL  - England
TA  - Fundam Clin Pharmacol
JT  - Fundamental & clinical pharmacology
JID - 8710411
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Methacrylates)
RN  - 57576-52-0 (Thromboxane A2)
RN  - 8SSC91326P (Donepezil)
RN  - L256JB984D (ozagrel)
SB  - IM
MH  - Animals
MH  - Dementia, Vascular/*drug therapy
MH  - Donepezil/administration & dosage/pharmacology/therapeutic use
MH  - Endothelium, Vascular/drug effects
MH  - Enzyme Inhibitors/administration & dosage/*pharmacology/therapeutic use
MH  - Female
MH  - Hyperhomocysteinemia/*drug therapy
MH  - Male
MH  - Maze Learning/drug effects
MH  - Methacrylates/administration & dosage/*pharmacology/therapeutic use
MH  - Rats
MH  - Rats, Wistar
MH  - Thromboxane A2/antagonists & inhibitors
OTO - NOTNLM
OT  - memory
OT  - oxidative stress
OT  - ozagrel
OT  - thromboxane A2
OT  - vascular dementia
EDAT- 2020/10/07 06:00
MHDA- 2021/12/21 06:00
CRDT- 2020/10/06 05:34
PHST- 2020/09/24 00:00 [revised]
PHST- 2020/06/22 00:00 [received]
PHST- 2020/09/29 00:00 [accepted]
PHST- 2020/10/07 06:00 [pubmed]
PHST- 2021/12/21 06:00 [medline]
PHST- 2020/10/06 05:34 [entrez]
AID - 10.1111/fcp.12610 [doi]
PST - ppublish
SO  - Fundam Clin Pharmacol. 2021 Aug;35(4):650-666. doi: 10.1111/fcp.12610. Epub 2020 
      Dec 5.