LCCP exposure leads to skin cell senescence damage by triggering oxidative stress mediated by mitochondrial Ca²⁺...

Currently, LCCP is widely present in environmental media as well as animal and human samples, suggesting that exposure to LCCP may have posed a threat to the health of animals and humans. Skin is one of the important pathways for LCCP exposure. To clarify the effects of LCCP exposure on the skin, we have utilized two skin cell models, HaCaT and L929, to investigate the complex impacts of LCCP exposure on skin cell senescence and its potential regulatory mechanism(s). Firstly, the expression of senescence-related markers, including SA-β-Gal staining, p16, p21, and p53 proteins, were evaluated, and the results showed that skin cell senescence occurred under the treatment of LCCP. Moreover, our findings revealed that LCCP exposure triggered the activation of the NF-κB signaling pathway, prompting an inflammatory response in skin cells. To further understand the potential molecular mechanism of skin cell senescence induced by LCCP, according to our preliminary experimental results, we hypothesized that mtROS and Ca²⁺ might have played an important role in the LCCP-induced senescence of skin cells. Based on this hypothesis, the use of mtROS and Ca²⁺ inhibitors revealed a reduction in LCCP-triggered cell senescence and oxidative stress, validating our speculation. Similarly, in vivo experiments showed that LCCP enhanced the expression of inflammatory factors in mouse skin tissue, inhibiting skin proliferation and collagen level. This discovery was consistent with the findings from in vitro experiments. In summary, our experiments emphasized that both in vitro and in vivo, exposure to LCCP could induce skin aging, potentially through oxidative stress mediated by Ca²⁺ overload, leading to skin aging damage. The research presented here establishes an important foundation for continued examination of the toxicology characteristics of LCCP.