Inhibitory action of antidiabetic drugs on the free radical production by the rod outer segment ectopic aerobic metabolism

Silvia Ravera, Federico Caicci, Paolo Degan, Davide Maggi, Lucia Manni, Alessandra Puddu, Massimo Nicolò, Carlo E. Traverso, Isabella Panfoli

Research output: Contribution to journalArticlepeer-review

Abstract

Rod outer segments (OS) express the Fo F1-ATP synthase and the respiratory chain, conducting an ectopic aerobic metabolism that produces free radicals in vitro. Diabetic retinopathy, a leading cause of vision loss, is associated with oxidative stress in the outer retina. Since metformin and glibenclamide, two anti-type 2 diabetes drugs, target the respiratory complexes, we studied the effect of these two drugs, individually or in association, on the free radical production in purified bovine rod OS. ATP synthesis, oxygen consumption, and oxidative stress production were assayed by luminometry, oximetry and flow cytometry, respectively. The expression of Fo F1-ATP synthase was studied by immunogold electron microscopy. Metformin had a hormetic effect on the OS complex I and ATP synthetic activities, being stimulatory at concentrations below 1 mM, and inhibitory above. Glibenclamide inhibited complexes I and III, as well as ATP production in a concentration-dependent manner. Maximal concentrations of both drugs inhibited the ROI production by the light-exposed OS. Data, consistent with the delaying effect of these drugs on the onset of diabetic retinopathy, suggest that a combination of the two drugs at the beginning of the treatment might reduce the oxidative stress production helping the endogenous antioxidant defences in avoiding retinal damage.

Original languageEnglish
Article number1133
Pages (from-to)1-13
Number of pages13
JournalAntioxidants
Volume9
Issue number11
DOIs
Publication statusPublished - Nov 2020

Keywords

  • Diabetic retinopathy
  • F F-ATP synthase
  • Glybenclamide
  • Light
  • Metformin
  • Oxidative stress
  • Reactive oxygen species and intermediates
  • Rod outer segment

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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