Prophylactic Instillation of Hydrogen-Rich Water Decreases Corneal Inflammation and Promotes Wound Healing by Activating Antioxidant Activity in a Rat Alkali Burn Model

Int J Mol Sci. 2022 Aug 29;23(17):9774. doi: 10.3390/ijms23179774.

Abstract

Many studies have demonstrated the therapeutic effects of hydrogen in pathological conditions such as inflammation; however, little is known about its prophylactic effects. The purpose of this study is to investigate the prophylactic effects of hydrogen-rich water instillation in a rat corneal alkali burn model. Hydrogen-rich water (hydrogen group) or physiological saline (vehicle group) was instilled continuously to the normal rat cornea for 5 min. At 6 h after instillation, the cornea was exposed to alkali. The area of corneal epithelial defect (CED) was measured every 6 h until 24 h after alkali exposure. In addition, at 6 and 24 h after injury, histological and immunohistochemical observations were made and real-time reverse transcription polymerase chain reaction (RT-PCR) was performed to investigate superoxide dismutase enzyme (SOD)1, SOD2, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) mRNA expression. CED at 12 h and the number of inflammatory infiltrating cells at 6 h after injury were significantly smaller in the hydrogen group than the vehicle group. Furthermore, SOD1 expression was significantly higher in the hydrogen group than the vehicle group at both 6 and 24 h, and the number of PGC-1α-positive cells was significantly larger in the hydrogen group than the vehicle group at 6 h after injury. In this model, prophylactic instillation of hydrogen-rich water suppressed alkali burn-induced inflammation, likely by upregulating expression of antioxidants such as SOD1 and PGC-1α. Hydrogen has not only therapeutic potential but also prophylactic effects that may suppress corneal scarring following injury and promote wound healing.

Keywords: PGC-1α; SOD1; alkali burn; antioxidant; antioxidative effect; corneal inflammation; hydrogen; prophylactic effect.

MeSH terms

  • Alkalies / pharmacology
  • Animals
  • Antioxidants / therapeutic use
  • Burns, Chemical* / drug therapy
  • Burns, Chemical* / metabolism
  • Corneal Injuries* / drug therapy
  • Disease Models, Animal
  • Eye Burns* / drug therapy
  • Hydrogen / pharmacology
  • Hydrogen / therapeutic use
  • Inflammation
  • Keratitis*
  • Rats
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / pharmacology
  • Superoxide Dismutase-1 / therapeutic use
  • Water / pharmacology
  • Wound Healing

Substances

  • Alkalies
  • Antioxidants
  • Water
  • Hydrogen
  • Superoxide Dismutase
  • Superoxide Dismutase-1

Grants and funding

This work was supported by a Grant-in-Aid for Scientific Research (KAKENHI, No. 21K09686) from the Japan Society for the Promotion of Science.