Toxicokinetic and liver proteomic study of the Chinese rare minnow (Gobiocypris rarus) exposed to F-53B

Abstract

Perfluorooctane sulfonic acid (PFOS) and its alternative 6:2 chlorinated polyfluoroethersulfonate (6:2 Cl-PFESA, also known as F-53B), are frequently detected in a variety of environmental and human samples. These substances have been associated with hepatotoxic effects, including disorders in lipid metabolism and oxidative stress. However, the molecular mechanisms underlying the causal relationship between exposure to F-53B and hepatotoxicity remain inadequately understood. This study investigated the toxicokinetics and mechanisms of hepatotoxicity associated with prolonged exposure to F-53B in adult Chinese rare minnows. Specifically, 5-month-old adult Chinese rare minnow was exposed to concentrations of 10 μg/L and 200 μg/L of F-53B for a duration of 28 days for bioaccumulation assessment, followed by a 14-day period for metabolic evaluation. The findings indicated that the bioaccumulation of F-53B in the tissues was positively correlated with the exposure concentrations. The logarithmic bioconcentration factor (Log BCF28d) was determined to be 2.67 ± 0.02 for the low concentration group and 2.27 ± 0.01 for the high concentration group. The calculated half-lives (t_1/2) were 18.50 ± 1.67 days and 21.38 ± 0.31 days for the respective concentration groups. F-53B protein exhibited a distinct tissue-specific distribution in adult Chinese rare minnow, with the following order of enrichment: Blood > Liver > Gonad > Gill > Intestine > Brain > Muscle. F-53B was primarily concentrated in the blood and liver, where the protein content was significantly higher. Exposure to F-53B for 28 days significantly elevated biochemical levels associated with lipid metabolism and increased the activities of the enzymes FAS, PPARα, and ACC in the liver. This exposure also resulted in impairment of the hepatic oxidative system in the Chinese rare minnow, with F-53B significantly reducing most of the measured markers related to oxidative stress (e.g., GSH, SOD, CAT, and MDA). Proteomic analysis indicated that the toxicity of F-53B regulates the expression of proteins across several functional classes. Based on the functional information of the differential proteins provided in UniProt and KEGG, they were categorized into five main categories: Cellular Processes, Environmental Information Processing, Genetic Information Processing, Metabolism, and Organismal Systems. This study indicate that F-53B is bioaccumulative and persistent in Chinese rare minnow, and can further induce oxidative stress and lipid metabolism disorders. Combined with proteomic research methods, the toxicological effects of F-53B on Chinese rare minnow can be better explained.