Jankovic Aleksandra, Ferreri Carla, Filipovic Milos, Ivanovic-Burmazovic Ivana, Stancic Ana, Otasevic Vesna, Korac Aleksandra, Buzadzic Biljana, Korac Bato
a Department of Physiology , Institute for Biological Research "Sinisa Stankovic", University of Belgrade , Belgrade , Serbia.
b ISOF, BioFreeRadicals Group, Consiglio Nazionale delle Ricerche , Bologna , Italy.
Free Radic Res. 2016 Nov;50(sup1):S51-S63. doi: 10.1080/10715762.2016.1232483. Epub 2016 Oct 25.
Setting the correct ratio of superoxide anion (O) 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 ) 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.
设定超氧阴离子（O）与一氧化氮（NO）自由基的正确比例，对于恢复糖尿病皮肤中被破坏的氧化还原信号以及改善NO的生理作用以预防和治疗糖尿病皮肤损伤似乎至关重要。在本研究中，我们检测了L-精氨酸和锰（II）-五氮杂大环超氧化物歧化酶（SOD）模拟物-M40403对糖尿病大鼠皮肤的影响。用四氧嘧啶诱导糖尿病（血糖水平≥12 mmol/l）后，将非糖尿病和糖尿病雄性米尔希尔杂种带帽大鼠分为三个亚组：（i）对照组，以及接受：（ii）L-精氨酸，（iii）M40403。糖尿病动物在诱导糖尿病后开始治疗，持续7天。与对照组相比，糖尿病皮肤的内皮型一氧化氮合酶（eNOS）、血红素加氧酶1（HO1）、锰超氧化物歧化酶（MnSOD）和谷胱甘肽过氧化物酶（GSH-Px）的皮肤免疫表达较低，同时NFE2相关因子2（Nrf2）和硝基酪氨酸水平升高。L-精氨酸和M40403治疗使四氧嘧啶诱导的硝基酪氨酸增加恢复正常。这分别伴随着L-精氨酸即SOD模拟物治疗后糖尿病皮肤中eNOS和HO1或MnSOD和GSH-Px蛋白表达水平的改善/恢复。结果表明，L-精氨酸和M40403可稳定糖尿病皮肤中的氧化还原平衡，并提示其潜在的分子机制。L-精氨酸和M40403恢复皮肤氧化还原平衡可能是改善糖尿病皮肤治疗的有效策略。
