Protective role of pyrroloquinoline quinone against gentamicin induced cochlear hair cell ototoxicity

J Appl Toxicol. 2024 Feb;44(2):235-244. doi: 10.1002/jat.4535. Epub 2023 Aug 31.

Abstract

Gentamicin (GM) is one of the commonly used antibiotics in the aminoglycoside class but is ototoxic, which constantly impacts the quality of human life. Pyrroloquinoline quinone (PQQ) as a redox cofactor produced by bacteria was found in soil and foods that exert an antioxidant and redox modulator. It is well documented that the PQQ can alleviate inflammatory responses and cytotoxicity. However, our understanding of PQQ in ototoxicity remains unclear. We reported that PQQ could protect against GM-induced ototoxicity in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells in vitro. To evaluate reactive oxygen species (ROS) production and mitochondrial function, ROS and JC-1 staining, oxygen consumption rate (OCR), and extracellular acidification rate (ECAR) measurements in living cells, mitochondrial dynamics analysis was performed. GM-mediated damage was performed by reducing the production of ROS and inhibiting mitochondria biogenesis and dynamics. PQQ ameliorated the cellular oxidative stress and recovered mitochondrial membrane potential, facilitating the recovery of mitochondrial biogenesis and dynamics. Our in vitro findings improve our understanding of the GM-induced ototoxicity with therapeutic implications for PQQ.

Keywords: cochlear hair cells; gentamicin; mitochondria; ototoxicity; pyrroloquinoline quinone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / metabolism
  • Apoptosis
  • Gentamicins* / metabolism
  • Hair Cells, Auditory / metabolism
  • Humans
  • Ototoxicity* / etiology
  • Ototoxicity* / metabolism
  • Ototoxicity* / prevention & control
  • PQQ Cofactor / metabolism
  • PQQ Cofactor / pharmacology
  • PQQ Cofactor / therapeutic use
  • Reactive Oxygen Species / metabolism

Substances

  • Gentamicins
  • Reactive Oxygen Species
  • PQQ Cofactor
  • Anti-Bacterial Agents