Thymol exposure mediates pro-oxidant shift by regulating Nrf2 and apoptotic events in zebrafish (Danio rerio) embryos

Manigandan Krishnan1, Dae Kwang Kim2, Se Gie Kim3

  • 1Department of Biotechnology, College of Engineering, Daegu University Kyoungsan, Kyoungbook 712-714, Republic of Korea.

Insights

Thymol (THY) exposure causes toxicity and teratogenic effects in zebrafish embryos by increasing reactive oxygen species (ROS) and disrupting cellular defense mechanisms and apoptosis. This study highlights ROS as a key mediator of THY-induced oxidative damage.

Area of Science:

  • Biochemistry
  • Toxicology
  • Developmental Biology

Background:

  • Oxidative stress is a key mechanism in chemical toxicity and disease.
  • Thymol (THY) has therapeutic uses, but its signaling pathways require further elucidation.
  • Understanding THY's impact on reactive oxygen species (ROS) is crucial for its mechanism of action.

Purpose of the Study:

  • To investigate the impact of Thymol (THY) on zebrafish embryos, focusing on ROS production.
  • To assess THY's toxicity, including teratogenic effects, survival rates, and cardiac function.
  • To analyze the molecular mechanisms underlying THY's effects on cellular defense and apoptotic pathways.

Main Methods:

  • Zebrafish embryos were exposed to varying concentrations of THY (25, 50, 100μM) for 96 hours post-fertilization.
  • Assessed survival rate (LC50), hatching, morphology, and cardiac function.
  • Measured ROS levels, mitochondrial membrane potential (ΔΨm), and expression of Nrf2, SOD-1, CAT, CYP450, and apoptotic markers (AIF, p53, Bax, Bcl-2, Casp-3, Casp-9).

Main Results:

  • THY exhibited significant toxicity, causing teratogenic effects and reducing survival rates (LC50 = 42.35μM).
  • THY exposure altered ROS levels, mitochondrial membrane potential, and the expression of key antioxidant and apoptotic proteins.
  • Significant modulatory effects were observed on cellular defense and apoptotic pathways.

Conclusions:

  • Reactive oxygen species (ROS) are identified as the primary mediators of Thymol (THY)-induced oxidative damage in zebrafish embryos.
  • THY disrupts cellular defense mechanisms and induces apoptotic events.
  • Findings provide insights into the toxicological mechanisms of THY and its impact on embryonic development.

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