ACTIVATED KUPFFER CELLS ATTENUATE THE LIVER RESPONSE TO THE PEROXISOME PROLIFERATOR PERFLUOROOCTANOIC ACID

It has been suggested that peroxisome proliferators stimulate Kupffer cells, an effect which may be involved in their mechanism of action. T o evaluate this hypothesis, this study was designed to investigate the effect of stimulating Kupffer cells on basal as well as induced perox isomal enzyme activity. Twenty four hours following treatment of male Sprague-Dawley rats with the peroxisome proliferating agent perfluoroo ctanoic acid (PFOA), in corn oil or with corn oil alone, hepatic perox isomal beta-oxidation was 4.6 +/- 0.2 and 1.8 +/- 0.1 U/g liver, respe ctively. As expected, PFOA did not influence the catalase activity. St imulating Kupffer cells in vivo by zymosan A (25 mg/kg, iv) prior to t reatment with corn oil or PFOA diminished basal as well as PFOA-induce d peroxisomal beta-oxidation by 20-35%. Activation of Kupffer cells by zymosan A also diminished catalase activity by over 60%. Furthermore, PFOA reduced blood colloidal carbon clearance by 35% within 2 h of it s administration. The data suggest that activation of Kupffer cells ex erts a negative effect on basal as well as PFOA-induced peroxisomal en zyme activities. Data also suggest that PFOA inhibits Kupffer cells. A ctivated Kupffer cells may indeed produce factors which interfere with normal hepatic peroxisomal functions and responses.