Aim. To assess the effect of melatonin (MT) on the content of lipid peroxidation (LPO) and protein oxidation (PO) products in the tissue homogenate from the burn wound in experimental thermal injury (TI).Materials and methods. Third-degree (IIIA) TI with a relative area of 3.5% was modeled on male Wistar rats via contact of the skin with boiling water. Intraperitoneal administration of MT (10 mg / kg) was performed once a day for 5 days. On days 5, 10, and 20, LPO products in the heptane and isopropanol phases of lipid extraction and PO products were determined in the tissue homogenate from the burn wound.Results. The content of secondary and end products of LPO in the heptane phase and end products in the isopropanol phase increased in the wound. The content of primary and secondary PO products of neutral nature increased on days 5, 10, and 20, and the level of secondary PO products of neutral nature elevated on days 10 and 20. Administration of MT reduced the content of LPO end products in the heptane phase, secondary and end products of LPO in the isopropanol phase, and the total amount of PO products due to primary and secondary products of neutral nature.Conclusion. In the 20-day follow-up, LPO and PO products accumulated in the burn wound. The administration of MT at a total dose of 50 mg / kg led to reduction and partial restoration of the content of LPO and POM products, which can limit secondary alterations and accelerate healing of the burn wound.
Разработка и патогенетическое обоснование новых подходов к локальной терапии термической травмы (ТТ) является актуальной и востребованной проблемой. В частности, представляет интерес разработка дермальных пленок (ДП), содержащих эндогенные регуляторы гомеостаза мультитропного действия. Цель исследования - оценка эффекта мелатонина (МТ) в составе оригинальной ДП на процессы репарации и содержание продуктов перекисного окисления липидов (ПОЛ) в коже очага повреждения при локальной термической травме. Методика. Эксперимент выполнен на 126 крысах-самцах Wistar. ТТ ІІІА степени площадью 3,5% моделировали погружением участка межлопаточной области кожи в очищенную воду с температурой 98-99 ºС на 12 с. МТ в составе ДП (0,005 г/г) на основе натрия карбоксиметилцеллюлозы наносили ежедневно после ТТ в течение 5 сут. На 5-е и 10-е сут после ТТ оценивали макроскопическую картину, площадь и глубину ожоговой раны, скорость ее эпителизации. Содержание продуктов ПОЛ в гомогенате кожи ожоговой раны определяли экстрационно-спектрофотометрическим методом в гептановой и изопропанольной фазах липидного экстракта. Результаты. Установлено, что накопление вторичных и конечных продуктов ПОЛ в гептановой и изопропанольной фазах липидного экстракта на 5-е и 10-е сут ассоциировано с площадью ожога. Применение оригинальной ДП с мелатонином приводит к снижению абсолютной и относительной площади ожога, увеличению скорости эпителизации ожоговой поверхности. На 5-е сут обнаружено снижение содержания вторичных и конечных продуктов ПОЛ в изопропанольной фазе, на 10-е сутки - снижение вторичных продуктов ПОЛ в гептановой фазе, конечных продуктов ПОЛ в изопропанольной фазе липидного экстракта. Заключение. Полученные результаты демонстрируют ускоряющий репарацию кожи в очаге ТТ эффект МТ в составе дермальной пленки за счет его ПОЛ-ограничивающего действия, расширяют представления о мультитропных эффектах МТ в организме и являются предпосылкой для применения ДП с МТ в клинической практике. Background. Development and pathogenetic justification of new approaches for local therapy of thermal trauma (TT) is a relevant and in-demand issue. Of special interest are dermal films (DF) containing endogenous pleiotropic regulators of homeostasis. Melatonin (MT) is one of such regulators that is suggested to be protective in TT. The aim of this study was to evaluate the effect of MT in the original DF on indexes of repair and concentration of lipid peroxidation (LPO) products in the injured skin after experimental TT. Methods. Experiments were performed on 126 Wistar male rats. Grade IIIA TT with an area of 3.5% was modeled by immersing a section of interscapular skin in purified water at a temperature of 98-99oC for 12 s. MT formulated into DF (0.005 g/g) based on sodium carboxymethylcellulose was applied after TT daily for 5 days. The macroscopic picture, area and depth of the burn wound, and the wound epithelization rate were evaluated on days 5 and 10 after TT. Concentration of LPO products in the injured skin homogenate was measured by extraction spectrophotometry in heptane and isopropanol phases of the lipid extract. Results. The accumulation of secondary and final LPO products in the heptane and isopropanol phases of the lipid extract on days 5 and 10 was associated with the burn area. The use of the original DF with MT resulted in a decrease in the absolute and relative areas of the burn and an increase in the rate of burn surface epithelialization. On day 5, a decrease in the content of secondary and final LPO products in the isopropanol phase was observed, and on day 10 decreases in secondary peroxidation products in the heptane phase and end LPO products in the isopropanol phase were detected. Conclusion. The results of this study demonstrated that MT formulated into DF accelerates skin repair in the TT focus due to its LPO-limiting effect, expands the understanding of MT pleiotropic effect, and represents a prerequisite for the clinical use of DF with MT.
Burn injuries are one of the key medical and social problems. Despite the significant achievements in combustiology, the slow healing and the appearance of infection are the key problems in burn patients, which lead to a longer hospitalization period, to reduction of life quality and to emotional disorders. Up to 70% of all complications after thermal trauma (TT) are connected with infection – first of all, pneumonia, infections of urinal tract. The forming of infectious complications, including sepsis, after TT is associated with excessive immunosuppressive reactions, as compensation for a long, stable proinflammatory response, in particular, owing to hyperproduction and effects of IL-10, IL-4, TGF-β. Aim: to study the influence of systemic and local usage of MT with original dermal film (DF) on reparation and serum cytokine concentration indicators in dynamics of experimental TT. The study was conducted using 84 rats – males of Wistar line, which were divided randomly into 4 groups: 1st group (n = 12) – intact monitoring, 2nd group (n = 30) – animals with TT, 3rd group (n = 21) – animals with TT and DF with MT use on the region of burn, 4th group (n = 21) – animals with TT and intraperitoneal injection of MT. To model TT of IIIA degree and relative area 3,5%, isolated skin area of interscapular area was immersed in distilled water at a temperature of 98-99 °С at 12 s. The DF with MT (at a concentration of 0.005 g/g) on 12 sm2 – area in 3rd group was used daily for 5 days. The MT was injected intraperitoneally daily at the dose of 10 mg/kg for 5 days. The wound area was calculated, the interleukin-4 (IL-4), tumor necrosis factor alpha (TNFα), interferon-gamma (IFNγ) were determined in serum on 5th,10th and 20th day from the moment of TT induction in each group. During experimental TT in dynamic monitoring from 5th to 20th day the absolute and relative areas of wound defect are reduced, because of that the epithelization speed and its part of area reduction are progressively increasing, on 5th,10th and 20th day the concentration of TNFα and IL-4 in serum is increasing with maximum values on 10th day of monitoring. Local usage of MT in DF during TT accelerates the healing of burn wound and lowers the TNFα and IL-4 concentration in serum on 5th, 10th and 20th day. Intraperitoneal use of MT during TT accelerates the healing of burn wound and lowers the TNFα and IL-4 concentration in serum on 5th and 20th day. The reparation accelerating effect of MT during TT is more expressed in locale usage in DF rather than using intraperitoneal injection.
Adaptive immunity changes in thermal trauma (TT) increase the risk of infectious complications and limit repair of the lesion. Hence, search and preclinical testing of effective and safe means to locally manage TT, containing bioregulators, is an urgent task of modern medicine. Dermal films (DF) are an innovative and popular variant of wound coatings for small-area burns, and pleiotropic properties of melatonin (MT) suggest its effectiveness in TT. The aim of the work is to investigate the effect of MT, as a component of original DF, upon the indexes of adaptive immunity in experimental TT. The experiment was performed on 115 male Wistar rats. Grade IIIA TT with area of 3.5% were produced by contact with boiling water for 12 s. DF with an area of 12 cm2 based on sodium carboxymethylcellulose contatning MT (5 mg/g) was applied daily for 5 days. Similar DF matrix, but without MT, was used in the control group, Amounts of CD3+ and CD45RA+ cells in blood, and lymphocyte subpolulations with early and late signs of apoptosis and partially necrotic cells were evaluated with flow cytofluorometer, as well as IgG and IgM concentrations were measured in blood serum using rat test systems. With TT, the amount of CD3+ in the blood decreases on days +5 and +10, CD45RA+, on days +5, +10 and +20, and the concentration of IgG in the serum, on days +5 and +10 of observation. On days +5 and +10 after TT, a relationship was established between CD3+ and the number of lymphocytes with signs of early apoptosis (R = -0.47; p 0.05; R = -0.51; p 0.05, respectively), and signs of late apoptosis and necrosis (R = -0.64; p 0.05; R = -0.42; p 0.05, respectively), between CD45RA+ and the number of lymphocytes with signs of early apoptosis (R = -0.47; p 0.05; R = -0.49; p 0.05, respectively), and signs of late apoptosis and necrosis (R = -0.57; p 0.05; R = -0.49; p 0.05, respectively). Usage of MT in DF composition leads to increase in blood CD3+ on the 5th and 20th days, CD45RA+, on the 5th day, and an increase in serum IgG concentration was observed on the 5th and 10th days following TT. Restriction of necrotic and apoptotic death of blood lymphocyte may be among the mechanisms of the immunotropic effect produced by MT which is, probably, due to its local antioxidant and anti-inflammatory action in the TT area.
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