S-542 Indomethacin aggravates the renal injury by inhibition of adenosine-medited renal protection in AKI = S-542 Indomethacin aggravates the renal injury by inhibition of adenosine-medited renal protection in AKI

다국어 초록 (Multilingual Abstract)

Background: Ischemia-reperfusion injury (IRI) is a leading cause of acute kidney injury with high morbidity and mortality due to limited therapy. AKI emerges in various clinical settings and is complex with outcome linking oxidative stress, inflammation, and cell death. Therefore protection of AKI is still an unsolved problem. Indomethacin is generally known that it inhibits the production of prostaglandins through the inhibition both cyclooxygenase (COX) 1 and 2. Prostaglandins have a wide variety of effect such as regulation of vasodilation, inflammation, regeneration, pain, fever. Therefore effect of indomethacin in AKI is different according to injury model. We investigated whether indomethacin which inhibits the production of prostaglandins aggravate the renal injury in AKI mouse model. Methods: Male C57/BL6 mice (8-10 weeks old, weight 20~25 g) were used. Acute kidney injury is induced by bilateral kidneys pedicle clamping which were subjected to 20 min or 30 min at both kidneys. Mice were treated with indomethacin at before and after injury. Blood and kidney samples were collected at 24 hr after IRI. The expression level of creatinine, N-gal & Kim-1 were detected in serum. And the expression level of PGE2, cAMP and adenosine were detected in kidney. Kidney Injury score were measured by HE staining and TUNEL. Results: In bilateral AKI model, Serum NGAL level and creatinine level were significantly highest in indomethacin treated group compared to non-treated group (NGAL, p＜0.05; creatinine, p＜0.01). Indomethacin treated group showed significantly more necrosis and apoptosis compared to non-treated group. Furthermore, Indomethacine inhibited the production of prostaglandins, cAMP and adenosine. Conclusions: Indomethacin inhibits adenosine-mediated renal protection by inhibition of prostaglandin production in AKI. Therefore Indomethacin worsened renal injury by inhibition of prostaglandin production in AKI. * This research was supported by a grant of the Korea Health Technology R&D Project through the KHIDI, funded by the Ministry of Health & Welfare, Republic of Korea (grant number :H15C2212)