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The effects of glycolipids and carbohydrates on bilirubin cytotoxicity in vitro.

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 microM bilirubin was incubated with 40-80 microM gangliosides (GM1, galactosyl-N-acetylgalactosaminyl-(N-acetylneuraminyl) galactosylglucosylceramide; GM2, N-acetylgalactosaminyl-(N-acetylneuraminyl)galactosylglucosylceramide; GM3, N-acetylneuraminylgalactosylglucosylceramide, and GD1a, N-acetylneuraminylgalactosyl-N-acetylgalactosaminyl-(N-acetylneura minyl) 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 greater than trihexosyl ceramide greater than lactosyl ceramide greater than 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.