Short-Term 6PPD-Q Exposure alters Tight-Junction-Related Gene Expression Without Acute Lethality in Japanese Medaka...

6PPD-quinone (6PPD-Q), a transformation product of the tire antioxidant 6PPD, causes acute mortality in several salmonid species, but its toxicity varies markedly among fish species. Disruption of vascular-barrier integrity and inflammatory signaling has been proposed as a key mechanism of 6PPD-Q toxicity. However, it remains unclear whether related transcriptional responses are specific to lethal effects. In this study, juvenile Japanese medaka (Oryzias latipes) aged 30-35 days post-hatch, an insensitive species, were exposed to 6PPD-Q at 31-500 μg/L to examine acute lethality and the expression of selected genes related to tight-junction function, inflammation, antioxidant defense, and neurotoxicity. No mortality or abnormal behavior was observed after 48 h of exposure at nominal concentrations up to 500 μg/L. After 24 h of exposure, the tight-junction-related genes cldn7, cldn15, and zo1 generally showed concentration-dependent increases at concentrations ranging from 62.5 to 500 μg/L. In contrast, the inflammation-related gene il1b was downregulated, whereas il8 was unaffected. Antioxidant- and neurotoxicity-related genes showed modest or nonmonotonic responses, including decreases in cat, gpx1, and ache. These results demonstrate that 6PPD-Q can alter tight-junction- and epithelial-barrier-related genes and other stress-response genes in medaka without causing overt acute toxicity. Thus, transcriptional changes in these genes alone are not sufficient predictors of acute lethality, although functional vascular-barrier disruption may remain a critical key event in sensitive salmonids.