Aggravating effect of atorvastatin on indomethacin-induced gastric injury: Focus on PGE(2), TNF-alpha, neutrophils and iNOS

作者：Yildirim F Ilkay Alp; Uyanik Ozge; Ozyogurtcu Hande; Gurel Aydin; Atukeren Pinar; Gumustas Koray; Ozdemir Osman; Uydes Dogan Sonmez^*

来源：Prostaglandins & Other Lipid Mediators, 2015, 121: 53-62.

DOI：10.1016/j.prostaglandins.2015.07.002

• Atorvastatin
• Indomethacin-induced gastric ulcer
• PGE(2)
• TNF-a
• Neutrophil infiltration
• iNOS

Statins are suggested to possess healing properties due to their antioxidant and antiinflammatory effects in animal ulcer models. In contrary, a clinical report indicated the formation of gastric ulcer by the use of atorvastatin. In this study, we aimed to investigate the effects of atorvastatin (0.5, 5 and 50 mg/kg, p.o.) after single (acute) and multiple (subchronic, 5 days) applications on indomethacin-induced gastric ulcer in rats. In both acute and subchronic models high dose atorvastatin (50 mg/kg), unlike to lower doses (0,5 and 5 mg/kg), significantly aggravated ulcer lesions induced by indomethacin (30 mg/kg) although, a direct ulcerogenic influence was lacking. Proulcerogenic effect of atorvastatin are likely to be associated with decreased mucosal defense mechanisms (GSH and PGE(2)), and increased neutrophil infiltration and proinflammatory factors (TNF-a and iNOS) possibly via independently from mevalonate pathway. Thus, atorvastatin therapy should be monitorized in patients for an increased risk of gastric ulcer particularly when used concomitantly with NSAIDs.

• 出版日期2015-9