Developmental toxicity of Nafion byproduct 2 (NBP2) in the Sprague-Dawley rat with comparisons to hexafluoropropylene oxide-dimer acid (HFPO-DA or GenX) and perfluorooctane sulfonate (PFOS)

Comparative Hepatotoxicity of a Novel Perfluoroalkyl Ether Sulfonic Acid, Nafion Byproduct 2 (H-PFMO2OSA), and Legacy Perfluorooctane Sulfonate (PFOS) in Adult Male Mice

“…Various toxicological studies have reported hepatomegaly in rodents, accompanied by increased ALT and AST levels, after exposure to legacy PFOS and novel PFESAs. ,− For example, compared with PFOS, 5 mg/kg/d 6:2 fluorotelomer sulfonic acid (6:2 FTSA) exposure in adult male CD1 mice for 28 days can induce moderate hepatotoxicity with increased relative liver weight and elevated serum AST . Then, exposure to H-PFMO2OSA (10 and 30 mg/kg/d) in pregnant Sprague–Dawley rats (from GD 8 to postnatal day 2) induces hepatocyte hypertrophy in maternal livers . Furthermore, exposure to PFOS in humans is positively associated with markers of liver function, including ALT and total bilirubin. , In the current study, both H-PFMO2OSA and PFOS exposure resulted in liver enlargement in male mice, with greater hepatomegaly induced by H-PFMO2OSA than PFOS.…”

“…Many studies have shown that PFASs, such as perfluorooctanoic acid and PFOS, can disturb lipid metabolism in rodents. − Of concern, PFASs exposure in humans may perturb TG and TC homeostasis. Multiple human epidemiological studies have reported positive associations between PFASs exposure and serum TC and TG concentrations, which are common comorbidities associated with NAFLD. ,, Furthermore, previous research has shown that changes in genes in maternal and fetal livers are associated with lipid metabolism in pregnant Sprague–Dawley rats following H-PFMO2OSA exposure (30 mg/kg) . In the current study, based on KEGG pathway analysis of shared proteins between the 1 mg/kg/d PFOS and H-PFMO2OSA groups, lipid metabolism, including fatty acid biosynthesis, degradation, and elongation, was the most significantly altered biological pathway.…”

“…33,34 Previous research has shown that exposure of pregnant Sprague−Dawley rats to H-PFMO2OSA from gestation day 14−18 can alter gene expression in the liver. 35 In this study, 24 DEPs involved in hepatic lipid metabolism were PPARα-dependent regulatory genes (Figure 3E). 36,37 In total, 13 DEPs were controlled by PPARγ (Figure S7), including nine DEPs shared with PPARα regulatory genes.…”

“…In contrast, TC content increased in the 5 mg/kg/d H-PFMO2OSA group (Table S2). Because of the structural similarity between PFASs and fatty acids, peroxisome proliferator-activated receptors (PPARs, including PPARα, PPARβ, and PPARγ), which are natural ligands of fatty acids, are the preferred targets of PFASs. , Previous research has shown that exposure of pregnant Sprague–Dawley rats to H-PFMO2OSA from gestation day 14–18 can alter gene expression in the liver . In this study, 24 DEPs involved in hepatic lipid metabolism were PPARα-dependent regulatory genes (Figure E). , In total, 13 DEPs were controlled by PPARγ (Figure S7), including nine DEPs shared with PPARα regulatory genes. − No lipid metabolism-related DEPs were regulated by PPARβ …”

“…45 Then, exposure to H-PFMO2OSA (10 and 30 mg/kg/d) in pregnant Sprague−Dawley rats (from GD 8 to postnatal day 2) induces hepatocyte hypertrophy in maternal livers. 35 Furthermore, exposure to PFOS in humans is positively associated with markers of liver function, including ALT and total bilirubin. 47,48 In the current study, both H-PFMO2OSA and PFOS exposure resulted in liver enlargement in male mice, with greater hepatomegaly induced by H-PFMO2OSA than PFOS.…”