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. 2020 May;28(5):574-581.
doi: 10.1016/j.jsps.2020.03.009. Epub 2020 Mar 20.

Possible combined effect of perindopril and Azilsartan in an experimental model of dementia in rats

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Possible combined effect of perindopril and Azilsartan in an experimental model of dementia in rats (V体育安卓版)

Yahya M Alzahrani et al. Saudi Pharm J. 2020 May.

Abstract (VSports注册入口)

Renin-angiotensin system exerted deleterious effects on learning and cognitive functions through different mechanisms. The present study has been designed to evaluate the protective effect of perindopril and azilsartan as monotherapy or in combination on aluminum chloride (AlCl3) induced neurobehavioral and pathological changes in Alzheimeric rats. Male Wistar rats were divided into nine groups (n = 6); negative control, AlCl3 treated, vehicle, AlCl3 and Azilsartan (3. 5 mg/kg, 7 mg/kg) co-treated, AlCl3 and perindopril (0. 5 mg/kg, 1 mg/kg) co-treated, AlCl3 and (Azilsartan 3. 5 mg/kg + perindopril 0. 5 mg/kg), and AlCl3 and (Azilsartan 7 mg/kg + perindopril 1 mg/kg), all groups were treated for consecutive 60 days. Then, memory function was evaluated by the Y- maze test VSports手机版. Amyloid Peptide - 42 (Aβ-42), Acetylcholinesterase (AChE), Malondialdehyde (MDA), Tumor necrosis factor (TNF-α) and Nitric Oxide (NO) levels in the hippocampus were assessed with (ELISA) kits. The histopathological studies of the hippocampal dentate gyrus (DG) and Cornu Ammonis-3 (CA3) were also performed. Oral administration of either azilsartan and perindopril alone or in combined for 60 days have shown; improvement of cognitive function, significant reduction in the hippocampal levels of Aβ-42, Acetylcholinesterase, Malondialdehyde (MDA), Tumor necrosis factor (TNF-α) and reserved most of histopathological changes in dentate gyrus (DG) and Cornu Ammonis-3 (CA3) that mediated by Alcl3. Our behavioral, biochemical, and histopathological studies indicate that perindopril and azilsartan have neuroprotective effects on the AD model of rats induced by AlCl3, suggesting that perindopril and azilsartan may be a candidate drugs for the treatment of AD. .

Keywords: Azilsartan; Dementia; Memory; Perindopril; Renin-angiotensin system. V体育安卓版.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

"V体育安卓版" Figures

Fig. 1
Fig. 1
Photomicrographs showing the hippocampus at the DG in the negative control group (a & b) with its layers; molecular (M) Granular (G) & Polymorphic (P). The granular cells are polyhedral with vesicular nuclei. In the positive control group (c & d), granular cells are vacuolated (dashed arrows), or shrunken with pyknotic nuclei (arrows). Neurofibrillary tangles (NFTs) and amyloid plaques (AP) are noted. Figure (A) shows low magnification of the hippocampus with DG marked (×4) (H&E stain. a & c ×200) (b &d × 600).
Fig. 2
Fig. 2
Photomicrographs of sections of the hippocampus at DG showing a normal histological structure, and normal granular cells with vesicular nuclei in groups treated with Perindopril dose 1 (0.5 mg/kg) (a & b) and perindopril dose 2 (1 mg/kg) (c & d) compared to sections hippocampus from the positive control group (e&f). (H &E stain . a,c &e × 200) (b,d &f × 600).
Fig. 3
Fig. 3
Photomicrographs of sections of the hippocampus at DG showing few scattered NFTs in groups treated with azilsartan dose 1 (3.5 mg/kg) (a &b) and only vacuolated cells (arrows) in group treated with azilsartan dose 2 (7 mg/kg) (c& d) compared to sections hippocampus from the positive control group (e&f). (H&E stain. a,c &e × 200) (b,d &f ×600).
Fig. 4
Fig. 4
Photomicrographs of sections of the hippocampus at DG showing scattered NFTs and vacuolated cells (dashed arrows) among the normal granular cells in combined Group 1 (azilsartan 3.5 mg/kg + perindopril 0.5 mg/kg) (a &b), on administrating (azilsartan 7 mg/kg + perindopril 1 mg/kg) in combined group 2 multiple NFTs were noted (c&d). This was in comparison to sections hippocampus from the positive control group (e&f). (H &E stain. a,c &e ×200) (b,d &f ×600).
Fig. 5
Fig. 5
Photomicrographs showing hippocampus at the CA3 in the negative control group (a&b) with its layers; molecular (M), pyramidal (py) & Polymorphic (p). The main polyhedral pyramidal cells show vesicular nuclei. In the positive control group (c&d), pyramidal cells are vacuolated (dashed arrows), or shrunken with pyknotic nuclei (arrows). NFTs and AP are noted. Figure (A) shows low magnification of the hippocampus with CA3 marked (H&E stain. a&c ×200) (b&d ×600).
Fig. 6
Fig. 6
Photomicrographs of sections of the hippocampus at CA3 showing a normal histological structure in groups treated with Perindopril dose 1 (0.5 mg/kg) (a &b) and perindopril dose 2 (1 mg/kg) (c & d) compared to sections hippocampus from the positive control group (e&f). (H &E stain . a,c &e ×200) (b,d &f ×600).
Fig. 7
Fig. 7
Photomicrographs of sections of the hippocampus at CA3 showing few scattered NFTs in groups treated with azilsartan dose 1 (3.5 mg/kg) (a &b). While, in group treated with azilsartan dose 2 (7 mg/kg) (c& d) pyramidal cells retained vesicular nuclei compared to sections hippocampus from the positive control group (e&f). (H &E stain. a,c &e ×200) (b,d &f ×600).
Fig. 8
Fig. 8
Photomicrographs sections of the hippocampus at CA3 in the combined group 1 (azilsartan 3.5 mg/kg + perindopril 0.5 mg/kg) (a &b) and combined group 2 (azilsartan 7 mg/kg + perindopril 1 mg/kg) (c&d) showing few NFT (arrows) among normal pyramidal cells .This is in comparison to sections of hippocampus in the positive control group (e&f). (H&E stain. a,c &e × 200) (b,d &f × 600).

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