EFFECT OF AGENTS WHICH MODIFY RETICULOENDOTHELIAL SYSTEM FUNCTION ON ACUTE PHALLOIDIN-INDUCED LETHALITY AND HEPATOTOXICITY IN MICE

The relationship between reticuloendothelial system (RES) function and acute phalloidin intoxication was studied in mice. Pretreatment with compounds that stimulate (zymosan) or depress (methyl palmitate and pr aseodymium nitrate, Pr(NO3)(3)) the RES resulted in protection against phalloidin-induced lethality and hepatotoxicity, as assessed by morph ological analysis. However, triolein (which stimulates the RES) was in effective against phalloidin. The timing of pretreatment with the effe ctive compounds showed a correlation between modified in vivo RES func tion (phagocytosis) and protection against the toxin. The effects of p retreatment with zymosan and Pr(NO3)(3) were further characterized. He patic damage induced by phalloidin was significantly decreased by thes e agents, as judged by morphological analysis as well as by serum aspa rtate aminotransferase and alanine aminotransferase release. This stud y also showed that there was no correlation between the capacity of Ku pffer cells to produce nitrite and prophylaxis against phalloidin. How ever, liver cell proliferation was increased by zymosan and Pr(NO3)(3) in parallel with protection against the toxin. Furthermore, freshly i solated hepatocytes from zymosan- or Pr(NO3)(3)-treated mice were less sensitive to phalloidin in vitro. These results indicate that the pro tective effect of these agents against phalloidin-induced hepatotoxici ty may be mediated by their mitogenic properties. (C) 1995 Academic Pr ess, Inc.