Plausibility of Daphnia magna as an alternative experimental model to evaluate effects on eicosanoid synthesis

Sangwoo Lee; Gun Tae Jung; Mina Cho; Jae Won Lee; Kojo Eghan; Jieon Lee; Seokjoo Yoon; Kwang Pyo Kim; Woo-Keun Kim

doi:10.1016/j.ecoenv.2023.115119

Plausibility of Daphnia magna as an alternative experimental model to evaluate effects on eicosanoid synthesis

Ecotoxicol Environ Saf. 2023 Jun 14:262:115119. doi: 10.1016/j.ecoenv.2023.115119. Online ahead of print.

Authors

Sangwoo Lee¹, Gun Tae Jung², Mina Cho¹, Jae Won Lee³, Kojo Eghan⁴, Jieon Lee¹, Seokjoo Yoon⁴, Kwang Pyo Kim⁵, Woo-Keun Kim⁶

Affiliations

¹ Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon 34114, the Republic of Korea.
² Department of Biomedical Science and Technology, Kyung Hee Medical Science Research Institute, Kyung Hee University, Seoul 02453, the Republic of Korea.
³ Department of Applied Chemistry, Institute of Natural Science, Global Center for Pharmaceutical Ingredient Materials, Kyung Hee University, Yongin 17104, the Republic of Korea.
⁴ Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon 34114, the Republic of Korea; Human and Environmental Toxicology, University of Science and Technology, Daejeon 34113, the Republic of Korea.
⁵ Department of Biomedical Science and Technology, Kyung Hee Medical Science Research Institute, Kyung Hee University, Seoul 02453, the Republic of Korea; Department of Applied Chemistry, Institute of Natural Science, Global Center for Pharmaceutical Ingredient Materials, Kyung Hee University, Yongin 17104, the Republic of Korea. Electronic address: kimkp@khu.ac.kr.
⁶ Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon 34114, the Republic of Korea; Human and Environmental Toxicology, University of Science and Technology, Daejeon 34113, the Republic of Korea. Electronic address: wookkim@kitox.re.kr.

PMID: 37327520
DOI: 10.1016/j.ecoenv.2023.115119

Abstract

Eicosanoids play important roles in inflammation, allergy, fever, and immune responses. In the eicosanoid pathway, cyclooxygenase (COX) catalyzes the conversion of arachidonic acid to prostaglandins and is a crucial target of nonsteroidal anti-inflammatory drugs (NSAIDs). Thus, toxicological studies on the eicosanoid pathway are important for drug discovery and the evaluation of adverse health outcomes due to environmental contaminants. However, experimental models are limited owing to concerns regarding ethical standards. Thus, new alternative models for evaluating toxic effects on the eicosanoid pathway must be developed. To this end, we adopted an invertebrate species, Daphnia magna, as an alternative model. D. magna was exposed to ibuprofen, a major NSAID, for 6 and 24 h. Transcription of eicosanoid-related genes (pla2, cox, pgd synthase, pgd2r2, ltb4dh, and lox) was analyzed by qPCR, eicosanoids (arachidonic acid, prostaglandin F2, dihydroxy prostaglandin F2, and 5-hydroxyeicosatetraenoate) were quantified by multiple reaction monitoring, and enzyme-linked immunosorbent assay was used to determine protein levels of arachidonic acid and prostaglandin E2 (PGE2). After 6 h of exposure, transcription of the pla2 and cox genes was downregulated. In addition, the whole-body level of arachidonic acid, an upstream of COX pathway, increased by over 1.5-fold. The levels of PGE2, a downstream of COX pathway, decreased after 24 h of exposure. According to our results, it is expected that the eicosanoid pathway might be conserved in D. magna, at least partially. This indicates the plausibility of D. magna as an alternative model for the screening of new drugs or chemical toxicity.

Keywords: COX inhibitor; Cladoceran; Daphnid; Eicosanoid pathway; Invertebrate.