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<p>Mycosporine-like amino acids (MAAs), nature’s most potent UV-absorbing substances, have antioxidant, anti-inflammatory, antiproliferative, and anti-aging properties. In the present study, we have isolated and characterized MAAs asterina-330, which conferred mitigating potential of the toxic effects of arsenic and fluoride in zebrafish hepatocytes. Exposure of Asterina-330 with toxicants arsenic and fluoride individually and in combination in zebrafish hepatocytes showed a significant decrease in reactive oxygen species (ROS), a subsequent increase in cell viability, and differential expression of Nrf2 and its related genes. The level of <i>nrf2</i> was up-regulated upon exposure to asterina-330. The Nrf2 activating capacity was also supported by the results of the cell viability assay by using an Nrf2 inhibitor, trigonelline, where trigonelline was found to neutralise the alleviating attribute of asterina-330. Further study revealed that asterina-330 could bind to the active residues of the DGR domain of Keap1 protein, which is responsible for the disruption of Nrf2-Keap1 interaction. Pharmacokinetic analysis shows drug-like properties of asterina-330, and it might be helpful as a beneficial ameliorating agent against arsenic and fluoride-induced toxic insults.</p>

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UV-absorbing compound asterina-330 mitigates the cytotoxic effect of arsenic and fluoride in zebrafish hepatocytes

  • 期刊论文

  • 发表日期：

    2025年6月25日

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  • Paritosh Mondal,
  • Animesh Sen,
  • Pallab Shaw,
  • Arpan Dey Bhowmik,
  • Sikha Mandal,
  • Ansuman Chattopadhyay,
  • Jnanendra Rath

摘要

Mycosporine-like amino acids (MAAs), nature’s most potent UV-absorbing substances, have antioxidant, anti-inflammatory, antiproliferative, and anti-aging properties. In the present study, we have isolated and characterized MAAs asterina-330, which conferred mitigating potential of the toxic effects of arsenic and fluoride in zebrafish hepatocytes. Exposure of Asterina-330 with toxicants arsenic and fluoride individually and in combination in zebrafish hepatocytes showed a significant decrease in reactive oxygen species (ROS), a subsequent increase in cell viability, and differential expression of Nrf2 and its related genes. The level of nrf2 was up-regulated upon exposure to asterina-330. The Nrf2 activating capacity was also supported by the results of the cell viability assay by using an Nrf2 inhibitor, trigonelline, where trigonelline was found to neutralise the alleviating attribute of asterina-330. Further study revealed that asterina-330 could bind to the active residues of the DGR domain of Keap1 protein, which is responsible for the disruption of Nrf2-Keap1 interaction. Pharmacokinetic analysis shows drug-like properties of asterina-330, and it might be helpful as a beneficial ameliorating agent against arsenic and fluoride-induced toxic insults.