Dietary antioxidants alleviate antibiotic-induced mitochondrial dysfunction through protein kinase AMP-activated

Jingyan Zhao1,2,3, Bing Shang2,3, Sha Xu2,3

  • 1Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, Zhengda Guangming International Eye Research Center, Qingdao Medicine College of Qingdao University, Qingdao, China.

PubMed
Abstract

Insights

Dietary antioxidants coniferaldehyde and raspberry ketone protect against antibiotic-induced mitochondrial damage and liver injury by modulating key cellular pathways. These compounds offer a potential therapeutic strategy for mitigating drug-induced toxicity.

Area of Science:

  • Cell Biology
  • Pharmacology
  • Toxicology

Background:

  • Antibiotic and ibuprofen combinations can induce mitochondrial and liver toxicity.
  • The underlying mechanisms involve mitochondrial dysfunction and oxidative stress.

Purpose of the Study:

  • To investigate the protective effects of dietary antioxidants against antibiotic-induced mitochondrial and hepatotoxicity.
  • To explore the involvement of protein kinase AMP-activated alpha (AMPKα) and nuclear factor erythroid 2-related factor 2 (NRF2) pathways.

Main Methods:

  • Human umbilical vein endothelial cells (HUVECs) were treated with antibiotics and ibuprofen, with or without antioxidants.
  • Mice models were used to evaluate drug-induced hepatotoxicity.
  • Mitochondrial parameters and key signaling proteins (AMPKα, GSK3B, NRF2, HO1) were analyzed.

Main Results:

  • Antibiotic/ibuprofen combinations led to mitochondrial fission, reactive oxygen species (ROS) overproduction, and mitofusin 2 downregulation.
  • Coniferaldehyde and raspberry ketone restored mitochondrial function and morphology in vitro.
  • These antioxidants prevented in vivo hepatotoxicity and inflammation by activating NRF2/HO1 and restoring AMPKα/GSK3B signaling.

Conclusions:

  • Coniferaldehyde and raspberry ketone demonstrate significant protective effects against antibiotic-induced hepatotoxicity.
  • The mechanism involves modulation of the AMPKα-GSK3B and NRF2-HO1 signaling pathways.
  • These antioxidants exhibit favorable safety profiles, suggesting therapeutic potential.

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