数字农科院2.0

C. Elegans as an in vivo model system for the phenotypic drug discovery for treating paraquat poisoning

文献类型： 外文期刊

作者： Ji P.; Li H.; Jin Y.; Peng Y.; Zhao L.; Wang X.

作者机构：

关键词： antidote; green fluorescent protein; malonaldehyde; reactive oxygen metabolite; ubidecarenone; animal experiment; animal model; Article; C57BL 6 mouse; Caenorhabditis elegans; controlled study; drug development; Escherichia coli; in vivo study; lifespan; lung parenchyma; male; mitochondrion; mouse; mouse model; nonhuman; paraquat poisoning; pharynx; phenotype; survival rate; validity; Biological organs; Coenzymes; Herbicides; Mitochondria; C elegan; Coenzyme Q10; Drug discovery; Elegans; In-vivo; Malondialdehyde; Mice models; Paraquat; Phenotypic drug discovery; Reactive oxygen species; Mammals

期刊名称： PeerJ

ISSN： 2167-8359

年卷期： 2022 年 10.0 卷

页码：

收录情况： SCIE（2022版）

摘要： Background. Paraquat (PQ) is an effective and widely used herbicide and causes numerous fatalities by accidental or voluntary ingestion. However, neither the final cytotoxic mechanism nor effective treatments for PQ poisoning have been discovered. Phenotypic drug discovery (PDD), which does not rely on the molecular mechanism of the diseases, is having a renaissance in recent years owing to its potential to address the incompletely understood complexity of diseases. Herein, the C. elegans PDD model was established to pave the way for the future phenotypic discovery of potential agents for treating PQ poisoning. Methods. C. elegans were treated with PQ-containing solid medium followed by statistical analysis of worm survival, pharyngeal pumping, and movement ability. Furthermore, coenzyme Q10 (CoQ10) was used to test the C. elegans model of PQ poisoning by measuring the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), mitochondrial morphology, and worm survival rate. Additionally, we used the classic mice model of PQ intoxication to evaluate the validity of the C. elegans model of PQ poisoning by measuring the effect of CoQ10 as a potential antidote for PQ poisoning. Results. In the C. elegans model of PQ poisoning, 5 mg/mL PQ increased the levels of ROS, MDA content, mitochondrial fragments, which significantly shortened the lifespan, while CoQ10 alleviated these phenotypes. In the mice model of PQ poisoning, CoQ10 increased the chance of survival in PQ poisoned mice while reducing ROS, MDA content in lung tissue and inhibiting PQ-induced lung edema. Moreover, CoQ10 alleviated the lung morphopathological changes induced by PQ. Conclusion. Here we established a C. elegans model of PQ poisoning, whose validity was confirmed by the classic mice model of PQ intoxication. Copyright © 2022 Ji et al.

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