Short-chain chlorinated paraffins may induce thymic aging in mice by activating PERK-CHOP.

Humans indirectly consume approximately 0.02 mg/kg/day of short-chained chlorinated paraffins (SCCPs) through the environment; however, the thymic senescence/damage induced by SCCPs has not been assessed. In this study, 16 female mice (4-week-old) per group were orally administered 0, 0.01, 0.1, and 1 mg/kg/day of SCCPs for 21 days, and the phenotypes and levels of superoxide dismutase (SOD), malondialdehyde (MDA), Tβ4, αβ TCR, SA-β-Gal, GRP78, PERK/CHOP, P53/P21, and CASPASE-1 of the thymus were assessed as indicators. Another group comprising 16 mice was killed at 4-week-old and these indicators were assessed. Thereafter, the thymuses cultured in vitro were exposed to 0, 14, 140, and 1400 μg/L SCCPs, respectively, and the above indicators were measured after 7-day. Based on the results, the oral administration of ≥0.01 mg/kg/day SCCPs to mice and ≥14 μg/L of SCCPs in medium caused thymic aging features, such as a decrease in the ratio of cortex to medulla, gradual blurring of the boundary between the cortex and medulla, dose-dependent oxidative stress (decreased SOD and increased MDA), and decreased levels of Tβ4 and αβ TCRs in the thymus. The oral administration of ≥1 mg/kg/day of SCCPs also impeded the growth and development of female mice and their thymuses. Exposure to the low levels of SCCPs activated PERK-CHOP in the mouse thymus, which modulated increases in SA-β-Gal, IL-1β, P53, and CASPASE-1 in vivo and in vitro. Overall, environmental levels and human blood concentrations (14.8-1400 μg/L) of SCCPs may induce mouse thymus senescence by activating PERK-CHOP in vivo and in vitro, respectively.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)