Effects of L-cysteine and reduced glutathione on the toxicities of microcystin LR: the effect for acute liver failure and inhibition of protein phosphatase 2A activity

We investigated the effects of L-cysteine (Cys) and reduced glutathione (GS H) on the liver toxicities of microcystin LR (MCLR). Ten milli-molar MCLR i n 10 mM Cys solution did not show acute liver toxicity of MCLR in mice. How ever, 10 mM MCLR in 10 mM GSH solution showed weaker acute toxicity of MCLR than intact MCLR. The CyS and GSH mixtures did not inhibit the activity of protein phosphatase 2A (PP 2A). In particular, the GSH mixture stimulated the acivity of PP 2A. These results refute the theory that inhibition of pr otein phosphatases by microcystins (MCs) leads to liver cell neucrosis. We concluded that the mechanism of acute toxicity in liver cells by MCs was di fferent from the mechanism of liver tumor promotion by MCs. Our findings sh ow the effects of Cys and GSH on acute liver toxicity of activity by MCLR ( C) 2000 Elsevier Science B.V. All rights reserved.