Immunomodulatory effect of candesartan on indomethacin-induced gastric ulcer in rats.
Non steroidal anti-inflammatory drugs (NSAIDs) induce gastric mucosal lesions in part by induction of oxidative stress as well as the activation of inflammatory cells and the production of proinflammatory cytokines. In this study, we examined the protective effect of candesartan (2 and 5 mg/kg) on indomethacin-induced gastric mucosa damage. Pretreatment with candesartan for 10 days reduced significantly the ulcer index induced by indomethacin injection. The preventive index of 2 mg/kg (76.74%) was higher than that of 5 mg/kg (65.11%). Both doses of candesartan were able to reduce significantly the stomach malondialdehyde content compared to indomethacin-treated group. Myeloperoxidase, tumor necrosis factor-α, cytokine-induced neutrophil chemoattractant gastric levels were significantly reduced by 2 mg/kg of candesartan more than 5 mg/kg. The Th1 cytokine interferon γ was also significantly reduced by both doses of candesartan compared to indomethacin injected group. On the other hand, indomethacin significant decreased the anti-inflammatory cytokine IL-10 gastric level. Pretreatment with candesartan (2 and 5 mg/kg) reversed this effect. In conclusion, the present study indicates that pretreatment with candesartan, can protect against the stomach injury induced by indomethacin through its antioxidant and immunomodulatory effects.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Helwan University, Ein Helwan, Cairo, Egypt.
Rehab
R
Kamel
Engy M
EM
El Morsy
Azza S
AS
Awad
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000276:immunology / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D007155:Immunologic Factors / Q000494:pharmacology*; D007213:Indomethacin / Q000009:adverse effects* / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000276:immunology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013777:Tetrazoles / Q000494:pharmacology*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000959:Antihypertensive Agents; D000975:Antioxidants; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D016207:Cytokines; D007155:Immunologic Factors; D013777:Tetrazoles; D008315:Malondialdehyde; C081643:candesartan; D007213:Indomethacin