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Hepatic Biotransformation of 2,2′,5-Trichlorobiphenyl (PCB18) Is Comparable in Germ-Free and Conventional Mice (Abstract ID: 274305)
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Hepatic Biotransformation of 2,2′,5-Trichlorobiphenyl (PCB18) Is Comparable in Germ-Free and Conventional Mice (Abstract ID: 274305)

Sean Brobston, Xuehsu Li, Youjun Suh, Hans-Joachim Lehmler and Julia Cui
The Journal of pharmacology and experimental therapeutics, Vol.393(5), 104883
05/2026
DOI: 10.1016/j.jpet.2026.104883

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Abstract

Polychlorinated biphenyls (PCBs) are persistent environmental contaminants with known toxicological effects. PCBs such as 2,2',5‑trichlorobiphenyl (PCB18) are metabolized by cytochrome P450-mediated hydroxylation primarily in the liver. However, the influence of the gut microbiome's metabolomic impact on PCBs has not been well characterized. Germ-free (GF) mice, which lack a native gut microbiome, are a common and effective method for assessing microbial significance. This study quantified PCB18 and its hydroxylated metabolites found in the livers of male and female conventional (CV) and GF C57BL/6 mice following oral exposure to PCB18 (6 mg/kg body weight for 3 consecutive days). Liver samples were homogenized and extracted using liquid-liquid extraction, and then analyzed using GC‑MS/MS. In addition to PCB18 and the metabolite 4′‑OH‑PCB18 (4′‑18), two unknown mono‑hydroxylated metabolites (X1‑18 and X2‑18) were consistently detected in the liver of both CV and GF mice. X2‑18 and 4′‑18 were the major metabolites, while X1‑18 appeared as a minor component. Although metabolite concentrations differed slightly across enterotypes, these differences did not show statistically significant differences in hepatic levels of PCB18 or its metabolites across sex or microbiome status. Quality assurance and control measures confirmed that the PCB extractions were efficient, reproducible, and accurate. These findings suggest that PCB18 undergoes similar degrees of hepatic biotransformation in CV and GF mice under the tested conditions.

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