Retinaldehyde Dehydrogenase Inhibition-Related Adverse Outcome Pathway: Potential Risk of Retinoic Acid Synthesis Inhibition during Embryogenesis
Retinoic acid (RA) is one of the factors crucial for cell growth, differentiation, and embryogenesis; it interacts with the retinoic acid receptor and retinoic acid X receptor to eventually regulate target gene expression in chordates. RA is transformed from retinaldehyde via oxidization by retinald...
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MDPI AG
2021-10-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/13/11/739 |
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| author | Kichul Cho Sang-Moo Lee Jina Heo Yong Min Kwon Dawoon Chung Woon-Jong Yu Seung Seob Bae Grace Choi Dae-Sung Lee Youngjun Kim |
| author_facet | Kichul Cho Sang-Moo Lee Jina Heo Yong Min Kwon Dawoon Chung Woon-Jong Yu Seung Seob Bae Grace Choi Dae-Sung Lee Youngjun Kim |
| author_sort | Kichul Cho |
| collection | DOAJ |
| description | Retinoic acid (RA) is one of the factors crucial for cell growth, differentiation, and embryogenesis; it interacts with the retinoic acid receptor and retinoic acid X receptor to eventually regulate target gene expression in chordates. RA is transformed from retinaldehyde via oxidization by retinaldehyde dehydrogenase (RALDH), which belongs to the family of oxidoreductases. Several chemicals, including disulphiram, diethylaminobenzaldehyde, and SB-210661, can effectively inhibit RALDH activity, potentially causing reproductive and developmental toxicity. The modes of action can be sequentially explained based on the molecular initiating event toward key events, and finally the adverse outcomes. Adverse outcome pathway (AOP) is a conceptual and theoretical framework that describes the sequential chain of casually liked events at different biological levels from molecular events to adverse effects. In the present review, we discussed a recently registered AOP (AOP<sub>297</sub>; inhibition of retinaldehyde dehydrogenase leads to population decline) to explain and support the weight of evidence for RALDH inhibition-related developmental toxicity using the existing knowledge. |
| first_indexed | 2024-03-10T05:01:43Z |
| format | Article |
| id | doaj.art-fb1ab93652a04703b866a2e1d40a8c86 |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-03-10T05:01:43Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-fb1ab93652a04703b866a2e1d40a8c862023-11-23T01:48:17ZengMDPI AGToxins2072-66512021-10-01131173910.3390/toxins13110739Retinaldehyde Dehydrogenase Inhibition-Related Adverse Outcome Pathway: Potential Risk of Retinoic Acid Synthesis Inhibition during EmbryogenesisKichul Cho0Sang-Moo Lee1Jina Heo2Yong Min Kwon3Dawoon Chung4Woon-Jong Yu5Seung Seob Bae6Grace Choi7Dae-Sung Lee8Youngjun Kim9Department of Genetic Resources Research, National Marine Biodiversity Institute of Korea (MABIK), Seocheon 33662, KoreaDepartment of Applied Bioscience, Dong-A University, Busan 49315, KoreaDepartment of Growth Engine Research, Chungbuk Research Institute (CRI), Chungju 28517, KoreaDepartment of Genetic Resources Research, National Marine Biodiversity Institute of Korea (MABIK), Seocheon 33662, KoreaDepartment of Genetic Resources Research, National Marine Biodiversity Institute of Korea (MABIK), Seocheon 33662, KoreaDepartment of Genetic Resources Research, National Marine Biodiversity Institute of Korea (MABIK), Seocheon 33662, KoreaDepartment of Genetic Resources Research, National Marine Biodiversity Institute of Korea (MABIK), Seocheon 33662, KoreaDepartment of Genetic Resources Research, National Marine Biodiversity Institute of Korea (MABIK), Seocheon 33662, KoreaDepartment of Genetic Resources Research, National Marine Biodiversity Institute of Korea (MABIK), Seocheon 33662, KoreaEnvironmental Safety Group, Korea Institute of Science and Technology (KIST) Europe, Campus E 7.1, 66123 Saarbrücken, GermanyRetinoic acid (RA) is one of the factors crucial for cell growth, differentiation, and embryogenesis; it interacts with the retinoic acid receptor and retinoic acid X receptor to eventually regulate target gene expression in chordates. RA is transformed from retinaldehyde via oxidization by retinaldehyde dehydrogenase (RALDH), which belongs to the family of oxidoreductases. Several chemicals, including disulphiram, diethylaminobenzaldehyde, and SB-210661, can effectively inhibit RALDH activity, potentially causing reproductive and developmental toxicity. The modes of action can be sequentially explained based on the molecular initiating event toward key events, and finally the adverse outcomes. Adverse outcome pathway (AOP) is a conceptual and theoretical framework that describes the sequential chain of casually liked events at different biological levels from molecular events to adverse effects. In the present review, we discussed a recently registered AOP (AOP<sub>297</sub>; inhibition of retinaldehyde dehydrogenase leads to population decline) to explain and support the weight of evidence for RALDH inhibition-related developmental toxicity using the existing knowledge.https://www.mdpi.com/2072-6651/13/11/739adverse outcome pathwayretinaldehyde dehydrogenaseretinoic acidembryogenesistoxicity |
| spellingShingle | Kichul Cho Sang-Moo Lee Jina Heo Yong Min Kwon Dawoon Chung Woon-Jong Yu Seung Seob Bae Grace Choi Dae-Sung Lee Youngjun Kim Retinaldehyde Dehydrogenase Inhibition-Related Adverse Outcome Pathway: Potential Risk of Retinoic Acid Synthesis Inhibition during Embryogenesis Toxins adverse outcome pathway retinaldehyde dehydrogenase retinoic acid embryogenesis toxicity |
| title | Retinaldehyde Dehydrogenase Inhibition-Related Adverse Outcome Pathway: Potential Risk of Retinoic Acid Synthesis Inhibition during Embryogenesis |
| title_full | Retinaldehyde Dehydrogenase Inhibition-Related Adverse Outcome Pathway: Potential Risk of Retinoic Acid Synthesis Inhibition during Embryogenesis |
| title_fullStr | Retinaldehyde Dehydrogenase Inhibition-Related Adverse Outcome Pathway: Potential Risk of Retinoic Acid Synthesis Inhibition during Embryogenesis |
| title_full_unstemmed | Retinaldehyde Dehydrogenase Inhibition-Related Adverse Outcome Pathway: Potential Risk of Retinoic Acid Synthesis Inhibition during Embryogenesis |
| title_short | Retinaldehyde Dehydrogenase Inhibition-Related Adverse Outcome Pathway: Potential Risk of Retinoic Acid Synthesis Inhibition during Embryogenesis |
| title_sort | retinaldehyde dehydrogenase inhibition related adverse outcome pathway potential risk of retinoic acid synthesis inhibition during embryogenesis |
| topic | adverse outcome pathway retinaldehyde dehydrogenase retinoic acid embryogenesis toxicity |
| url | https://www.mdpi.com/2072-6651/13/11/739 |
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