In vitro and in vivo studies of the toxic effects of perfluorononanoic acid on rat hepatocytes and Kupffer cells

This study investigated the toxic effects of perfluorononanoic acid (PFNA), a persistent organic pollutant, on rat hepatocytes and Kupffer cells in vitro and in vivo. The results showed that administration of 5 μM PFNA increased the viabilities of the hepatocytes and the Kupffer cells. An exposure of 50 μM PFNA did not alter the viabilities of both cells, as well as the release of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) from the primary cultured hepatocytes or the hepatocytes co-cultured with Kupffer cells. An exposure of 100 μM PFNA only decreased the viability of the hepatocytes. The administration of PFNA changed the hepatocyte expression of several genes related to lipid metabolism in vitro and in vivo. Oil Red O Staining revealed that 5 mg PFNA/kg/D treatment lead to dramatic accumulation of lipids in rat liver. At the same dose PFNA damaged hepatocytes histopathologically. Up-regulated expressions of the inflammatory cytokines occurred in the Kupffer cells treated with 50 μM PFNA and in the livers of the rat receiving a 5 mg PFNA/kg/D treatment. In addition, these cytokines also increased in serum of the rat receiving higher dose of PFNA. In summary, on the one hand, PFNA exposure affected the viability of the hepatocytes, hepatic lipid metabolism and lead to lipid accumulation in liver. On the other hand, for the first time, PFNA exposure was demonstrated to affect the viability of the Kupffer cells as well as their expression of cytokines, which involved in regulation of various liver functions. Therefore, we conclude that both the hepatocyte and the Kupffer cell contribute to the observed hepatotoxicity of PFNA.

► An exposure of 100 μM PFNA decreased the viability of the hepatocytes, but not the Kupffer cells, in vitro.
► 5 mg/kg/D PFNA treatment increased the inflammatory cytokines in serum of rats.
► The exposure of PFNA altered the expression of genes related to lipid metabolism and inflammation.