Peroxynitrite-induced toxicity in cultured astrocytes.

The exposure of cultured astrocytes to peroxynitrite (ONOO-) for 40 min resulted in a concentration-dependent increase in the release of lactate dehydrogenase from the cells into the bathing medium over the following 24 h. Control experiments showed that the breakdown products of ONOO- contribute, to some extent, to its ability to cause cell death but that the drug vehicle (0.3 M NaOH), which increased the pH of the bathing medium to 9.4, had little effect. The cytotoxic action of ONOO- was mimicked by 3-morpholinosydnonimine (SIN-1) which liberates both nitric oxide (NO) and superoxide but not by S-nitrosoglutathione which liberates only NO. SIN-1-induced cytotoxicity was reversed in a concentration-dependent manner by superoxide dismutase and attenuated by haemoglobin suggesting that the effect of SIN-1 is due, at least in part, to the formation of ONOO-.