Toxicology letters · 2025
Research on the therapeutic effects of recombinant protein PON1Q/R192 intervention on mice poisoned by different categories of organophosphorus compounds.
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Zhou Shuang, Cui Yue, Li Lu, Zhang Pengsi, Zhu Zhe, Yuan Li, Zhao Min
Аннотация
Organophosphorus compounds are widely used in agriculture, but their poisoning poses a great threat. This study focuses on exploring the therapeutic effects of rePON1Q192 and rePON1R192 on mice poisoned with different types of organophosphorus compounds. These two recombinant proteins are prepared via gene synthesis into the pET - 32a vector and expression in E. coli BL21.Organophosphorus compounds are divided into two groups by structure: one group contained a pyrimidine ring (similar in structure to diazinon), and the other group contained multiple chlorine atoms (similar in structure to chlorpyrifos). Each group included a control group, a rePON1Q/R192 control group, a poisoned group, and a rePON1Q/R192 treatment group. Kaplan-Meier survival analysis assessed the 12-h survival proportion of mice per group. Use ELISA to detect IL - 6 expression, HE staining to assess lung and brain injuries, TUNEL staining to observe apoptosis in brain and lung tissues, and electron microscopy to examine mitochondrial structural changes in brain tissues and alterations in lung tissues of each group. The results showed that rePON1Q/R192 could improve the clinical manifestations of mice with organophosphorus poisoning, increase the survival proportion, reduce the release of the inflammatory factor IL - 6, alleviate the pathological damage of brain and lung tissues, as well as mitochondrial damage. The number of apoptotic cells in the brain and lung tissues of mice in the rePON1Q/R192 treatment group was significantly reduced. In animal experiments, the therapeutic effects vary: rePON1Q192 is better for diazinon poisoning, while rePON1R192 is better for chlorpyrifos-like poisoning. Thus, the therapeutic effects of rePON1Q192 and rePON1R192 vary depending on the type of organophosphorus poison, likely due to differences in their molecular structures.