#6485 UNI-494 LOWERS URINARY B2-MICROGLOBULIN LEVELS IN RATS

Abstract Background and Aims Mitochondrial dysfunction in renal cells play a critical role the pathophysiology of acute kidney injury (AKI) chronic disease (CKD). The proximal tubule is primary sensor effector CKD progression AKI. measurement urine Β2-microglobulin (Β2M) sensitive assay for injury. Nicorandil, selective mitochondrial ATP-sensitive potassium channel activator, may be promising AKI treatment, but its clinical use limited by serious gastrointestinal side effects rapid absorption elimination. UNI-494, novel nicorandil prodrug designed to improve pharmacologic properties, increase short half-life safety profile nicorandil. This study presents efficacy data on UNI-494 rat ischemia-reperfusion (I/R) model, evaluating biomarkers Method 49 male Sprague-Dawley rats were randomly assigned 4 groups evaluate vivo bilateral model. Group 1, Sham group, consisted 10 subjects while 2–4 each had 13. 1 received no 2 vehicle, 3 10mg/kg 20mg/kg UNI-494. Treatments administered as single dose Day 0, hour prior modeling. Body weights measured Days -1, 1. Urine Β2M levels urinary albumin-to-creatinine ratio (UACR) samples collected within 24 hours after surgery using metabolic cages. Serum blood urea nitrogen (BUN) creatinine -1 (pre-modeling) T-tests used statistical differences between groups. Results significantly lower 20 mg/kg group compared vehicle content both (10 mg/kg) was (Fig. 1). than There difference body weight changes group. statistically significant among all serum BUN pre-modeling UACR. Conclusion Lower higher other indicate that have renoprotective effect. Additionally, dose-response trend. Our results are consistent with previously published similar model I/R. potential effect should further investigated.