No abstract

Antioxidant properties of recombinant peroxiredoxin-6 and chimeric protein PSH combining peroxidase and superoxide dismutase activities were studied on the model of retrograde perfusion of isolated rat heart under conditions of H2O2-induced oxidative stress. The exogenous antioxidant proteins exhibited cardioprotective properties manifested in heart rate normalization, maintenance of contractile activity of the myocardium, and prevention of H2O2-induced LPO in oxidative stress. Localization of peroxiredoxin-6 and PSH in the cardiac tissue was determined and myocardial structures most effectively protected by the antioxidant enzymes from ischemia/reperfusion-induced damages were identified. The results suggest that modified peroxiredoxins are promising components of perfusion media for preservation of isolated organs.

Although many different classes of antioxidants have been evaluated as radioprotectors, none of them are in widespread clinical use because of their low efficiency. The goal of our study was to evaluate the potential of the antioxidant protein peroxiredoxin 6 (Prdx6) to increase the radioresistance of 3T3 fibroblasts when Prdx6 was applied after exposure to 6 Gy X-ray. In the present study, we analyzed the mRNA expression profiles of genes associated with proliferation, apoptosis, cellular stress, senescence, and the production of corresponding proteins from biological samples after exposure of 3T3 cells to X-ray radiation and application of Prdx6. Our results suggested that Prdx6 treatment normalized p53 and NF-κB/p65 expression, p21 levels, DNA repair-associated genes (XRCC4, XRCC5, H2AX, Apex1), TLR expression, cytokine production (TNF-α and IL-6), and apoptosis, as evidenced by decreased caspase 3 level in irradiated 3T3 cells. In addition, Prdx6 treatment reduced senescence, as evidenced by the decreased percentage of SA-β-Gal positive cells in cultured 3T3 fibroblasts. Importantly, the activity of the NRF2 gene, an important regulator of the antioxidant cellular machinery, was completely suppressed by irradiation but was restored by post-irradiation Prdx6 treatment. These data support the radioprotective therapeutic efficacy of Prdx6.

Различные ожоги органов дыхания сопровождаются массовой гибелью клеток эпителиальных тканей (слизистые трахеи, бронхов), что приводит к исклю-чительно тяжелым последствиям для здоровья чело-века. Поэтому чрезвычайно важным является созда-ние новых лекарственных препаратов для лечения такого вида травм.Острые патологические процессы в организме сопровождаются мощным окислительным стрессом (гиперпродукция активных форм кислорода -АФК), который является одним из основных пора-жающих факторов, при этом лавинообразное неко-нтролируемое развитие процесса образования АФК представляет собой огромную потенциальную опас-ность. Одним из решающих факторов при регенера-ции поврежденного эпителия является восстановле-ние баланса оксиданты-антиоксиданты, а вариант восстановления такого баланса -использование различных антиоксидантов. В настоящее время име-ется довольно широкий ассортимент таких веществ, в основном низкомолекулярных. В последнее время достаточное внимание уделяется более эффектив-ным по своей способности нейтрализовать АФК ферментам-антиоксидантам по сравнению с низко-молекулярными антиоксидантами [1][2][3][4][5][6]. Особое место занимает фермент-антиоксидант пероксире-доксин-6 (Prx-6). Ранее было показано, что он явля-ется основным ферментом-антиоксидантом в трахее и бронхах легких у различных млекопитающих, включая человека [7][8][9]. Уровень его экспрессии в эпителии трахеи существенно зависит от степени поражения эпителия [10], что и служит основанием Effects of different antioxidant enzymes on the tracheal epithelium regeneration after chemical burn SummaryThe aim of the study was to investigate a role of different antioxidant enzymes for tracheal epithelium regeneration after chemical burn.Methods. The study was conducted in a rat model of chemical burn of the upper airways caused by inhaled hydrochloric acid.Results. According to results of histological examination, to the 2 nd day after the exposure approximately 70 % of the epithelial surface remained injured, mostly due to death of the ciliated cells. The degree of the damage was unchanged to the 4 th day after the exposure. Visible regeneration of the tracheal epithelium began to the 7 th day. The death of the tracheal epithelial cells was generally due to necrosis though cell apoptosis also occurred. The expression of all antioxidant enzymes was greatly decreased during the 1st day after the exposure followed by its growth to maximum to the 7 th day and normal level to the 15 th day after the burn. Exposition of superoxide dismutase to the trachea resulted in a significant epithelium destruction. On contrary, peroxiredoxin 6 and a chimeric protein containing peroxiredoxin / superoxide dismutase significantly protected the tracheal epithelium. Conclusion. Peroxiredoxins and their derivates could be used as highly efficient therapeutic agents with potent antioxidant action in patients with burn injury of the upper airways. Key words: oxidative stress, antioxidant enzymes, peroxiredoxin, tracheal epithelium, chemical burn. РезюмеПроведено исследование...

Study was performed using a rat model of thermal burn of upper respiratory tract (URT). The URT burn in rats was induced by intratracheal instillation of 70 °C water vapor using a micro-vapor generator. In a week after the intervention about 50 % of the ciliated epithelium was destructed. In 2 weeks after the intervention the inflammatory response enhanced and tissue edema increased. In 4 weeks after the intervention partial irregular restoration of tracheal epithelium cells was observed. Both IL-1 and IL-4 expression did not change significantly during restoration of tracheal epithelium, but IL-8 and IL-10 expression increased and was high even 1 month after the burn. Simultaneously, dramatic increase in expression of peroxyredoxine 6, which is the main antioxidant protein in trachea, was observed during regeneration of trachea epithelium. Iimmunohistochemical investigations showed that the increase in peroxyredoxine 6 in trachea during the regeneration of trachea epithelium after the burn could be related to increased peroxyredoxine expression in goblet cells. Therefore, activation of peroxyredoxine 6 synthesis by goblet cells appears to be the key step in activation of epithelium defense systems after thermal burn.