Alteration of Kupffer cell function and morphology by low melt point paraffin wax in female Fischer-344 but not Sprague-Dawley rats

This study was conducted to compare the effects of 60-day dietary exposure (2%) to low melt point paraffin wax (LMPW) on both general liver morphology and Kupffer cell (KC) function and morphology in female F-344 and Sprague- Dawley (SD) rats. Livers from only F-344 rats fed LMPW had granuloma format ion/lymphoid cell aggregates with small areas of necrosis. Significant incr eases in serum alanine and aspartate aminotransferase as well as gamma-glut amyltransferase activities were detected only in treated F-344 rats. Additi onally, detectable amounts of LMPW were present only in livers of treated F -344 rats. Because KC can be involved in granuloma formation, their morphol ogy and function were examined. Electron microscopy revealed the presence o f large, irregularly shaped, membrane-asssociated vacuoles in cells isolate d from F-344 rats exposed to LMPW. These vacuoles were not seen in KC from control rats and rarely detected in KC isolated from LMPW-exposed SD rats. Moreover, indices of ECC function including phagocytic activity and nitric oxide and superoxide anion production were significantly increased by KC is olated from F-344 rats exposed to LMPW (1.6-, 36-, and 2.2-fold increases, respectively) over untreated controls. In contrast, LPS-stimulated producti on of TNF and LTB4 was significantly decreased only in KC of LMPW-fed F-344 rats. No significant changes in these functions were observed in KC isolat ed from SD rats exposed to LMPW or from KC isolated from control F-344 or S D rats. These data provide evidence that dietary LMPW alters the morphology and functional capacity of KC of F-344 but not SD rats and these changes m ay ultimately lead to granuloma formation. (C) 1998 Society of Toxicology.