The Effects of Glycolipids and Carbohydrates on Bilirubin Cytotoxicity in vitro

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Abstract
We have studied the inhibitory effects of various glycolipids including gangliosides and carbohydrates on bilirubin cytotoxicity towards human glia cells using a 51Cr release assay. All cytotoxic activity was abolished when 100 μM bilirubin was incubated with 40–80 μM gangliosides (GM1 galactosyl-N-acetylgalactosaminyl-(N-acetylneuraminyl)galactosylglucosylceramide; GM2, N-acetylgalactosaminyl-(N-acetylneuraminyl)galactosylglucosylceramide; GM3, N-acetylneuraminylgalactosylglucosylceramide, and GD1 a, N-acetylneuraminylgalactosyl-N-acetylgalactosaminyl -(N-acetylneuraminyl)galactosylglucosylceramide). On the other hand, inhibition by asialoglycolipids was less effective than that by gangliosides, but became more effective with increasing numbers of sugars per molecule, the efficacy of inhibition being as follows: globoside > trihexosyl ceramide > lactosyl ceramide > glucosyl ceramide. Glucosyl ceramide and the carbohydrates of neuramine lactose or N-acetylneuraminic acid (NANA) did not have inhibitory effects. These results suggest that the terminal acidic group of NANA and the numbers of sugar chains in glycolipids play important roles in the inhibition of bilirubin cytotoxicity.