New mechanism of immune damage in marine medaka induced by pentachlorophenol exposure

Pentachlorophenol (PCP) is a persistent organic pollutant commonly found in marine environments, and recent studies have confirmed its detrimental effects on the immune systems of aquatic organisms. To date, however, the potential molecular mechanisms and subsequent downstream damage caused by PCP remain poorly understood.

In a study published in KeAi's Journal of Environmental Chemistry and Ecotoxicology, a team of researchers from China proposed a novel immunotoxicity mechanism for PCP in marine organisms. They found that PCP induces immune-inflammatory responses in marine medaka by activating the TLR signaling pathway, and they discussed the associated downstream damage.

"This is the first effort to reveal the impact of PCP on the immune system of marine medaka," says senior and corresponding author Professor Zhang Huanxin. "We discovered that PCP triggers inflammatory responses in the immune system by activating the Toll-like receptor signaling pathway. At the same time, it disrupts metabolic processes and induces oxidative stress, leading to liver damage and, ultimately, compromising immune function."

The study combines transcriptomics, metabolomics, biochemical and histopathological analyses, as well as molecular docking and kinetic simulations, to investigate the immunotoxic effects of PCP.

"The results showed that PCP, even at environmentally relevant concentrations (1 and 10 µg/L), activates the TLR signaling pathway, significantly upregulating pro-inflammatory cytokines and triggering inflammatory responses," says Zhang.

Using the adverse outcome pathway (AOP) framework, the binding of PCP to TLR5 was identified as the molecular initiating event. This event triggers a cascade of key events, including activation of the TLR signaling pathway, enhanced inflammation, increased oxidative stress, disrupted amino acid metabolism, liver injury, and ultimately, impaired immune system function.

By introducing the AOP framework, the team analyzed the immunotoxic process of PCP in marine medaka. "In addition to the previously reported immunotoxicity of PCP in marine algae and invertebrates, our findings further demonstrates that environmentally relevant concentrations of PCP can also cause significant immune damage to marine fish, providing new theoretical insights into the mechanisms of PCP-induced immunotoxicity across different trophic levels in marine organisms," adds Zhang.

Contact author name, affiliation, email address:

Huanxin Zhang, College of Geography and Environment, Shandong Normal University, Jinan, 250014, Shandong, China.

E-mail: qshdzhhx@sdnu.edu.cn

Funder:

This study was financially supported by the National Natural Science Foundation of China (No. 42471081); the Shandong Province Young Taishan Scholar, China (No. tsqn202507153); the Shandong Provincial Natural Science Foundation, China (No. ZR2021YQ22); and the Shandong Province Young Taishan Scholar, China (No. tsqn202312155).

Conflict of 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.

See the article:

Zhang, Y.; Chu, J.; Cui, S.; Kong, Q.; Cui, L.; Zhou, Y.; Yao, S.; Zhang, Y.; Zhang, H. Deciphering the TLR-Mediated Immunotoxic Adverse Outcome Pathway of Pentachlorophenol in Marine Medaka (Oryzias Melastigma). Environmental Chemistry and Ecotoxicology 2026, 8, 486–496. https://doi.org/10.1016/j.enceco.2025.11.039.