Neuroprotection of taurine against bilirubin-induced elevation of apoptosis and intracellular free calcium ion in vivo.

Abstract

Previous work has shown that taurine protected neurons against unconjugated bilirubin (UCB)-induced neurotoxicity by preventing cell apoptosis and maintaining intracellular Ca²⁺ homeostasis in primary neuron culture. This study investigates the neurotoxicity of hyperbilirubinemia and neuroprotection of taurine in a clinically relevant murine model in vivo. A hyperbilirubinemia baby mice model was established by intraperitoneal injection with UCB. After 24 h, the neural apoptotic level, transcriptional activity of caspase-3, and iCa²⁺ concentration were detected. It was found that UCB injection significantly increased both intracellular free Ca²⁺ concentrations and the activities of proapoptosis protease caspase-3, which is related to the elevation of neural apoptosis level. When baby mice were pretreated with 7.5 or 15 mg/kg body weight (bw) taurine for 4 h and then exposed to UCB, apoptotic death was significantly attenuated through down-regulation of activity of caspase-3 and i[Ca²⁺] in the brain. From these observations, it was concluded that taurine limits bilirubin-induced neural damage by inhibiting iCa²⁺ overload as well as decreasing activation of proapoptotic proteases caspase-3. This study might contribute to the development of taurine as a broad-spectrum agent for preventing and/or treating neural damage in neonatal jaundice.