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.