Ibuprofen Augments Bilirubin Toxicity in Rat Cortical Neuronal Culture

摘要: Premature infants are at risk for bilirubin-associated brain damage. In cell cultures bilirubin causes neuronal apoptosis and necrosis. Ibuprofen is used to close the ductus arteriosus, often given when hyperbilirubinemia its maximum. Ibu- profen known interfere with bilirubin-albumin binding. We hypothesized that toxicity cultured rat embryonic cortical neurons augmented by coincubation ibuprofen. Incubation ibuprofen above a concentration of 125 g/mL reduced viability, measured methylthiazole tetrazolium reduction, 68% controls (p 0.05). Lactate dehydrogenase (LDH) release in- creased from 29 38% 0.01). The vehicle solution did not affect viability. Coincubation 10 M unconjugated (UCB)/human serum albumin in molar ratio 3:1 250 caused additional loss viability increased LDH 0.01), DNA fragmentation, activated caspase-3. Preincubation pan-caspase inhibitor z-val-ala- asp-fluoromethyl ketone abolished ibuprofen- UCB-induced fragmentation. study demonstrates low reduces neuron increases this effect. Apoptosis underlying death mech- anism. (Pediatr Res 65: 392-396, 2009)