Piperlongumine treatment impacts heart and liver development and causes developmental delay in zebrafish (Danio rerio) embryos

• Published in: Ecotoxicology and environmental safety 2023-06, Vol.258, p.114995-114995, Article 114995
• Main Authors: Jeon, Hwang-Ju, Kim, Chaeeun, Kim, Kyeongnam, Lee, Sung-Eun
• Format: Article
• Language: English
• Subjects: Abnormal heart development; Animals; Embryo, Nonmammalian; Humans; Liver; Pericardium; Piperlongumine; Transgenic zebrafish; Water Pollutants, Chemical - metabolism; Zebrafish - metabolism; Zebrafish embryos
• ISSN: 0147-6513; 1090-2414
• DOI: 10.1016/j.ecoenv.2023.114995

Piperlongumine (PL) and piperine (PP) are alkaloids presented in long pepper (Piper longum), and they exhibit various biological activities, especially anti-cancer properties. With these regards, they are considered as future medicines with high potential. Even they are exposed to humans such a long time, their potential toxicities in the environment have not been studied. Therefore, their ecological toxicities were assessed using zebrafish embryos. PP showed low mortality and no abnormal phenotype up to 10 µM. However, PL exhibited strong acute toxicity at the concentration of 5–10 µM ranges, and abnormal development were frequently found in the range of 1–2.5 µM with pericardial and yolk sac edemas. In transgenic zebrafish embryos, PL induced an increase in the number of intersegmental vessels and delayed the early-stage development. PL treatment affected heart formation and heart rate. The presence of PL induced the expression of cytokines, inflammatory markers, and inflammasome in the embryos. The PL treatment changed the mRNA levels of the ER stress and apoptosis-related genes. In addition, ROS production was observed during early-stage development of PL-treated zebrafish embryos. These results indicate that developing PL as a medicine would require extremely meticulous strategies to prevent potential toxicity. [Display omitted] •Piperlongumine (PL) showed strong acute toxicity from the treated concentration of 5 μM.•PL causes severe morphological changes as pericardial and yolk sac edema at 2.5 μM.•PL treatment refers abnormal cardiac formation and reduces heart beat rates.•PL treatment causes abnormal liver formation in a transgenic zebrafish line.•PL changed mRNA expression of genes in relation to ER stress and heart formation.