Bilirubin-induced apoptosis in cultured rat neural cells is aggravated by chenodeoxycholic acid but prevented by ursodeoxycholic acid.

作者: Rui F.M. Silva , Cecı́lia M.P. Rodrigues , Dora Brites

DOI: 10.1016/S0168-8278(01)00015-0

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摘要: Abstract Background/Aims : Unconjugated bilirubin (UCB) can be neurotoxic in jaundiced neonates and patients with Crigler–Najjar syndrome. UCB toxicity may culminate cell death, however, the occurrence of apoptosis has never been investigated. Ursodeoxycholic acid (UDCA) is a strong modulator apoptotic threshold both hepatic nonhepatic cells. The aims this study were to determine whether plays role neural death induced by UCB, investigate ability UDCA prevent death. Methods Cultured rat astrocytes incubated (17 86 μ M) plus albumin (5.7 28.7 ;M) for 4–22 h. In addition, neurones treated either 50 M UDCA, or their combination 4 Cultures scored nonviable cells trypan blue dye exclusion. Apoptosis was assessed Hoechst staining terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labelling assay. Results concentration- time-dependent decrease astrocyte viability. 4- 7-fold increased after h exposure 17 ;M respectively ( P ). reduced Cholic not protective, chenodeoxyholic aggravated Finally, showed 1.5-fold greater sensitivity than while still protective. Conclusions toxic neurones, causing through an process. Moreover, inhibits UCB-induced could mimicked other bile acids.

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