Protective effects of perindopril against indomethacin-induced gastric mucosal damage through modulation of DDAH-1/ADMA and ACE-2/ANG-(1-7) signaling pathways.
Drug Chem Toxicol
; 45(6): 2509-2518, 2022 Nov.
Article
em En
| MEDLINE
| ID: mdl-34384315
ABSTRACT
Indomethacin is a widely used nonsteroidal anti-inflammatory drug; however, its clinical utility is accompanied by serious adverse reactions including peptic ulcers. The current study aims to investigate the protective potential of perindopril against indomethacin-induced gastric injury in rats. Perindopril (4 mg/kg) was administered orally for 7 days and indomethacin (60 mg/kg, single oral dose) was administered on the 7th day, 1 h after perindopril administration. Pantoprazole was used as a standard agent. Ulcer index (UI), preventive index ratio (PI), histopathological examination, oxidative stress, and inflammatory biomarkers were investigated. Perindopril significantly decreased UI while increased PI and counteracted histopathological aberrations induced by indomethacin. It alleviated indomethacin-induced oxidative stress by lowering NO while increasing GSH content and superoxide dismutase activity. Perindopril significantly downregulated TNF-α and asymmetric dimethylarginine (ADMA), while significantly upregulated COX-2, PGE-2, dimethylarginine dimethylaminohydrolase-1 (DDAH-1), ANG-(1-7), and ACE-2 expression. Together, these findings suggest the gastroprotective effects of perindopril through modulation of DDAH-1/ADMA and ACE-2/ANG-(1-7) signaling.HIGHLIGHTSPerindopril attenuated gastric histopathological damage.It increased GSH content and SOD activity while decreased NO content.It modulated gastric ADMA and DDAH-1 activity.It reduced TNF-α, while increased COX-2 and PGE-2 expression.It upregulated ACE-2 activity and ANG-(1-7) protein expression.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Indometacina
/
Perindopril
Limite:
Animals
Idioma:
En
Revista:
Drug Chem Toxicol
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Egito