TY - JOUR
T1 - Inhibitory action of antidiabetic drugs on the free radical production by the rod outer segment ectopic aerobic metabolism
AU - Ravera, Silvia
AU - Caicci, Federico
AU - Degan, Paolo
AU - Maggi, Davide
AU - Manni, Lucia
AU - Puddu, Alessandra
AU - Nicolò, Massimo
AU - Traverso, Carlo E.
AU - Panfoli, Isabella
N1 - Funding Information:
Funding: This research was funded by Unige Funding grants for research.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/11
Y1 - 2020/11
N2 - 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.
AB - 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.
KW - Diabetic retinopathy
KW - F F-ATP synthase
KW - Glybenclamide
KW - Light
KW - Metformin
KW - Oxidative stress
KW - Reactive oxygen species and intermediates
KW - Rod outer segment
UR - http://www.scopus.com/inward/record.url?scp=85096063537&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85096063537&partnerID=8YFLogxK
U2 - 10.3390/antiox9111133
DO - 10.3390/antiox9111133
M3 - Article
AN - SCOPUS:85096063537
VL - 9
SP - 1
EP - 13
JO - Antioxidants
JF - Antioxidants
SN - 2076-3921
IS - 11
M1 - 1133
ER -