The Carbon Number-specific Impact of Mineral Oil Saturated Hydrocarbons on Inducing Colonic Inflammation in Female and Male Fischer 344 Rats

This study investigated the effects of mineral oil saturated hydrocarbon (MOSH) sub-fractions (C 20-30 and C 30-50 ) on the colon of male and female F344 rats and the underlying mechanisms. Due to its specific accumulation in the colon, the C 20-30 sub-fraction, particularly at a high dose (15 g/kg), elicited mucosal epithelial detachment and loss of intestinal glands in both sexes after 6 months of exposure. These pathological changes were accompanied by corresponding shifts in biomarkers indicative of increased inflammation (IL-1β, IL-2, TNF-α), oxidative stress (SOD, MDA), and impaired tight junction function (ZO-1, claudin-1, occludin), potentially mediated by the suppression of the Keap1/Nrf2 signaling pathway. Fecal metabolomics further revealed that exposure to either sub-fraction altered metabolites and metabolic pathways in a sex- and dose-dependent manner. The most significantly enriched differential pathways were cysteine and methionine metabolism in females and glutathione metabolism in males. Collectively, these findings provide new evidence for the colon-specific risks of MOSH sub-fractions.