Hydrogen-rich saline reduces cell death through inhibition of DNA oxidative stress and overactivation of poly (ADP-ribose) polymerase-1 in retinal ischemia-reperfusion injury

Mol Med Rep. 2015 Aug;12(2):2495-502. doi: 10.3892/mmr.2015.3731. Epub 2015 May 5.

Abstract

Overactivation of poly (ADP-ribose) polymerase 1 (PARP-1), as a result of sustained DNA oxidation in ischemia-reperfusion injury, triggers programmed cell necrosis and apoptosis. The present study was conducted to demonstrate whether hydrogen-rich saline (HRS) has a neuroprotective effect on retinal ischemia reperfusion (RIR) injury through inhibition of PARP-1 activation. RIR was induced by transient elevation of intraocular pressure in rats. HRS (5 ml/kg) was administered peritoneally every day from the beginning of reperfusion in RIR rats until the rats were sacrificed. Retinal damage and cell death was determined using hematoxylin and eosin and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. DNA oxidative stress was evaluated by immunofluorescence staining of 8-hydroxy-2-deoxyguanosine. In addition, the expression of PARP-1 and caspase-3 was investigated by western blot analysis and/or immunohistochemical staining. The results demonstrated that HRS administration improved morphological alterations and reduced apoptosis following RIR injury. Furthermore, the present study found that HRS alleviated DNA oxidation and PARP-1 overactivation in RIR rats. HRS can protect RIR injury by inhibition of PARP-1, which may be involved in DNA oxidative stress and caspase-3-mediated apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • DNA Fragmentation / drug effects
  • Eosine Yellowish-(YS)
  • Gene Expression Regulation
  • Hematoxylin
  • Hydrogen / pharmacology*
  • In Situ Nick-End Labeling
  • Injections, Intraperitoneal
  • Intraocular Pressure / drug effects
  • Male
  • Oxidation-Reduction
  • Oxidative Stress / drug effects
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases / genetics*
  • Poly(ADP-ribose) Polymerases / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / enzymology
  • Reperfusion Injury / genetics
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*
  • Retina / drug effects*
  • Retina / enzymology
  • Retina / metabolism
  • Signal Transduction
  • Sodium Chloride / pharmacology*

Substances

  • Sodium Chloride
  • Hydrogen
  • Parp1 protein, rat
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases
  • Casp3 protein, rat
  • Caspase 3
  • Eosine Yellowish-(YS)
  • Hematoxylin