Targeting the superoxide/nitric oxide ratio by L-arginine and SOD mimic in diabetic rat skin.
Setting the correct ratio of superoxide anion (O2•-) and nitric oxide (•NO) radicals seems to be crucial in restoring disrupted redox signaling in diabetic skin and improvement of•NO physiological action for prevention and treatment of skin injuries in diabetes. In this study we examined the effects of L-arginine and manganese(II)-pentaazamacrocyclic superoxide dismutase (SOD) mimic - M40403 in diabetic rat skin. Following induction of diabetes by alloxan (blood glucose level ≥12 mMol l-1) non-diabetic and diabetic male Mill Hill hybrid hooded rats were divided into three subgroups: (i) control, and receiving: (ii) L-arginine, (iii) M40403. Treatment of diabetic animals started after diabetes induction and lasted for 7 days. Compared to control, lower cutaneous immuno-expression of endothelial NO synthase (eNOS), heme oxygenase 1 (HO1), manganese SOD (MnSOD) and glutathione peroxidase (GSH-Px), in parallel with increased NFE2-related factor 2 (Nrf2) and nitrotyrosine levels characterized diabetic skin. L-arginine and M40403 treatments normalized alloxan-induced increase in nitrotyrosine. This was accompanied by the improvement/restitution of eNOS and HO1 or MnSOD and GSH-Px protein expression levels in diabetic skin following L-arginine, i.e. SOD mimic treatments, respectively. The results indicate that L-arginine and M40403 stabilize redox balance in diabetic skin and suggest the underlying molecular mechanisms. Restitution of skin redox balance by L-arginine and M40403 may represent an effective strategy to ameliorate therapy of diabetic skin.
a Department of Physiology , Institute for Biological Research "Sinisa Stankovic", University of Belgrade , Belgrade , Serbia.
Aleksandra
A
Jankovic
b ISOF, BioFreeRadicals Group, Consiglio Nazionale delle Ricerche , Bologna , Italy.
Carla
C
Ferreri
c CNRS, Institute of Biochemistry and Cellular Genetics, Université de Bordeaux , Bordeaux , France.
Milos
M
Filipovic
d Department of Chemistry and Pharmacy , Friedrich-Alexander-University of Erlangen-Nürnberg , Erlangen , Germany.
Ivana
I
Ivanovic-Burmazovic
a Department of Physiology , Institute for Biological Research "Sinisa Stankovic", University of Belgrade , Belgrade , Serbia.
Ana
A
Stancic
a Department of Physiology , Institute for Biological Research "Sinisa Stankovic", University of Belgrade , Belgrade , Serbia.
Vesna
V
Otasevic
e Faculty of Biology , Centre for Electron Microscopy, University of Belgrade , Belgrade , Serbia.
Aleksandra
A
Korac
a Department of Physiology , Institute for Biological Research "Sinisa Stankovic", University of Belgrade , Belgrade , Serbia.
Biljana
B
Buzadzic
a Department of Physiology , Institute for Biological Research "Sinisa Stankovic", University of Belgrade , Belgrade , Serbia.|e Faculty of Biology , Centre for Electron Microscopy, University of Belgrade , Belgrade , Serbia.
Bato
B
Korac
D000818:Animals; D001120:Arginine / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D013481:Superoxides / Q000378:metabolism*
D013481:Superoxides; D009569:Nitric Oxide; D001120:Arginine
Diabetes; SOD mimic; nitric oxide; redox balance; skin; superoxide