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. To evaluate this hypothesis, this study was designed to investigate the effect of stimulating Kupffer cells on basal as well as induced peroxisomal enzyme activity. Twenty four hours following treatment of male Sprague-Dawley rats with the peroxisome proliferating agent perfluorooctanoic acid (PFOA), in corn oil or with corn oil alone, hepatic peroxisomal beta-oxidation was 4.6 +/- 0.2 and 1.8 +/- 0.1 U/g liver, respectively. As expected, PFOA did not influence the catalase activity. Stimulating Kupffer cells in vivo by zymosan A (25 mg/kg, i.v.) prior to treatment with corn oil or PFOA diminished basal as well as PFOA-induced 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 its administration. The data suggest that activation of Kupffer cells exerts a negative effect on basal as well as PFOA-induced peroxisomal enzyme activities. Data also suggest that PFOA inhibits Kupffer cells. Activated Kupffer cells may indeed produce factors which interfere with normal hepatic peroxisomal functions and responses.