Comparative study on changes in serum amino acid metabolic profiles in mice exposed to perfluorooctanoic acid and sodium ρ-perfluorous nonenoxybenzene sulfonate

Perfluorinated compounds (PFCs) such as perfluorooctanoic acid (PFOA) and sodium ρ-perfluorous nonenoxybenzene sulfonate (OBS) are toxic to organisms, but their toxicological differences in affecting serum amino acid metabolism remain unclear. To investigate the effects of subchronic PFOA and OBS exposure on mice’s serum amino acid metabolic profile and explore their toxicological differences. Fifteen healthy male C57BL/6N mice were randomly divided into three groups: control (CON) group, PFOA group (exposed to 3 mg/(kg·d) PFOA), and OBS group (exposed to 3 mg/(kg·d) OBS). The experiment was conducted continuously for four weeks. After the exposure period, serum samples were collected, and the concentrations of free amino acids and their derivatives in the serum were determined using an automatic amino acid analyzer. Principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) were used for data analysis. PCA and OPLS-DA results showed distinct intra-group clustering and clear inter-group separation of the serum amino acid metabolic profiles. A total of 23 differential amino acids and their derivatives were identified with the criterion of variable importance in projection (VIP) > 1.0. Quantitative analysis indicated that neither PFOA nor OBS exposure significantly altered the total serum amino acid levels in mice, but both selectively disrupted the metabolic homeostasis of specific amino acids and their derivatives. For essential amino acids, exposure to either PFOA or OBS significantly increased serum leucine levels; serum threonine levels were significantly decreased in the PFOA group but increased in the OBS group. For non-essential amino acids, the levels of serine, asparagine, and glutamine in the OBS group were significantly higher than those in both the CON and PFOA groups. Regarding amino acid derivatives, 11 compounds showed highly significant differences (P < 0.01) and 3 showed significant differences (P < 0.05) among the three groups. Subchronic exposure to both PFOA and OBS significantly disrupts the serum amino acid metabolic profile in mice. However, the two compounds exhibited distinct effects: OBS exerted a broader impact on non-essential amino acids (serine, asparagine, glutamine), while PFOA showed a stronger association with cardiovascular and muscle toxicity markers (homocysteine, 1-methylhistidine). These findings suggest that PFOA and OBS may exert toxic effects through different molecular mechanisms.