Оцінка та корекція адаптаційних можливостей організму за умов одночасного впливу стрес-чинників хімічної природи

Диссертация на соискание ученой степени кандидата медицинских наук по специальности 14.03.03 - нормальная физиология, Львовский национальный медицинский университет имени Данила Галицкого. - Львов, 2005.

Диссертация посвящена обоснованию коррекции и повышения адаптационных возможностей организма и биопрофилактики нарушения гомеостаза при длительном одновременном комбинированном действии химических стресс-факторов свинца и фтора путем комплексного использования биопротекторов пектина, кальция и триовита. Установлено, что длительное влияние свинца и фтора приводит к нарушению прооксидантно-антиоксидантного равновесия ткани печени и крови, нарушению функционального состояния печени и порфиринового обмена, торможения безусловно-рефлекторной деятельности и эмоциональной реактивности животных, снижения содержания кальция в сыворотке крови. Выявлено особенности развития указанных изменений и ультраструктуры печени до и после использования биопротекторов, закономерности накопления в организме свинца и выведения фтора, типы их комбинированного действия, фазовость протекания адаптации. Предложен метод интегральной оценки антиоксидантной защиты при действии химических стресс-факторов, критерии оценки динамики адаптационно-компенсаторных процессов, способ повышения функциональных резервов организма и адаптивной биопрофилактики дезадаптационных состояний при комбинированном действии свинца и фтора.

Ключевые слова: адаптация, биопрофилактика, коррекция, свинец, фтор, комбинированное действие, пектин, кальций, триовит.

Annotation

Yu.V. Fedorenko Evaluation and correction of adaptive resources of the organism under simultaneous influence of chemical stress-factors (at the example of lead and fluorine). - Manuscript.

Dissertation seeking the scientific degree of Candidate of Medical Sciences, specialty 14.03.03 - Normal Physiology. Lviv National Medical University named after Danylo Halytsky. - Lviv, 2004.

The dissertation is dedicated to substantiation of correction and increasing of adaptive resources of the organism and bioprophylaxis of impaired homeostasis under prolonged combined action of chemical stress-factors (lead and fluorine) by complex application of bioprotectors, such as pectin, calcium and triovit. The peculiarities of the metabolic and structural changes and the course of adaptive processes have been studied in parallel in separate and combined action of the substances without and with continuous administration of the fore mentioned bioprotectors based on the mathematical planning of the experiment with evaluation of combined action by regression equations. Modeling of disadaptative conditions was performed by daily oral administration lead nitrate (36 mg/kg of body weight) and sodium fluoride (10 mg/kg of body weight) and their combination in subchronic experiments on male white rats. In order to prevent the formation of PbF2 in vitro the substances were administered with an interval of 1,5-2 hours in the sequence “lead-fluorine”. The bioprotectors were added to the ration of the animals.

It was estimated that lead, fluorine and their joint entry lead to the gradual decrease in adaptive resources of the organism, which occurred due to the disbalance in the lipid peroxidation and antioxidant protection systems, disruptions of calcium and porphyrine metabolism, manifestations of hepatotoxic and neurotoxic, ultrastructural changes of hepatic tissue. The maximal changes were found in combined action of the substances on the 30th day of the experiment, which was confirmed by accumulation of lead in biosubstrates and high fluorine content in urine. In hepatic tissue and in blood an increase in dienic conjugates and TBA-active products, decrease of superoxidedismutase and catalase activity was found. The peculiarity of a prolonged combined action of the substances compared to their separate action was inhibition of lipid peroxidation products formation in decreased antiradical and antiperoxidative protection, which testifies the low adaptive-compensatory capabilities of the organism. Thus impairment of the adaptive protection mechanisms of the stress-limiting antioxidant system was detected. The dynamics of changes of activity of alanin- and aspartatetransaminase, alkaline phosphatase and urea content in blood was characterized by wave-like and multidirectional patterns of change, which indicate the phase course of adaptation. Disruption of calcium homeostasis was accompanied by the least level of calcium in combined entry of the substances. The separate action of lead, the action of fluorine to a lesser extent was causing inhibition of unconditional reflex activity and conduction of nerve signals, decrease of emotional reactivity of animals. A decrease of the content of ascorbic acid in the adrenals which indicates the decrease of the non-enzymatic link of the antioxidant status and is an indirect index of the decrease of the adaptive reactions of the organism. An increase in д-aminolevulenic acid (ALA) excretion with urine in the action of lead and augmentation of the effect of fluorine, which promotes the complication of adaptive process course. It was shown that fluorine promotes the increase of lead level in biosubstrates, and lead decreases the excretion of fluorine-ion with urine.

The protective role of pectin, pectin with calcium and the complex of pectin with calcium and triovit. It was found that pectin prophylaxis is the most effective in the first half of the experiments primarily in the action of lead ad the least effective in the action of fluorine and a prolonged administration of lead. Improvement of the parameters in combined action occurred due to the decrease of the action of lead alone. The efficacy of pectin prophylaxis is decreasing in the direction “lead > lead + fluorine > fluorine”. Calcium with pectin was found to be the most effective agent to correct all three modeled disadaptation conditions, directed upon the mechanism of both substances studied: the gain of peroxidation products under the action of substances and inhibitory processes of diene conjugate formation in combined action were both decreased, the catalase activity increased, the calcium content and alkaline phosphatase activity in blood serum have become virtually normal, the parameters of nervous system activity significantly improved, urine excretion of д-ALA and fluorine has also dropped. It was proven that triovit with pectin and calcium exert a synergetic action in adaptive bioprophylaxis, effectively activate metabolic processes, decrease the action potency of lead and fluorine and their combination by augmenting the functional capacity of the organism. Application of the complex activate central and local stress-limiting systems of adaptive protection, normalizes most of the studied effects, decreases lead concentration in bones 3,3 times, delta-АLA in urine - 6 times, fluoride - 5-6 times. The phasal course of adaptive reactions is characterized by the detection of wave-form and multidirectional changes of the effects, different types of combined activity by the effects studied. The very character of the combined action depends on the registered effect, the strength and duration of the stress-factor's action and the bioprotector used and can serve as a criterion for evaluation of the dynamics of adaptive-compensatory processes in correction of the disadaptation conditions, caused by a combination of substances. A new method of integral evaluation of antioxidant protection in xenobiotic action was suggested. The author has grounded the optimal mode of correction of adaptive process and increasing of functional reserves of organism and adaptive bioprophylaxis of homeostasis disturbances of the organism in a prolonged simultaneous input of lead and fluorine.

Key words: bioprophylaxis, pectin, calcium, triovit, lead, fluorine, combined action, disadaptation, adaptive-compensatory processes.

Перелік умовних скорочень

д-АЛК (д-АLА)- дельтаамінолевулінова кислота (aminolevyline acid)

АлАТ - аланінамінотрансфераза

АОЗ - антиоксидантний захист

АсАТ - аспартатамінотрансфераза

ДК - дієнові кон'югати

КД - комбінована дія

КТЛ - каталаза

ЛД50 - середня смертельна доза

ЛФ - лужна фосфатаза

МДА - малоновий діальдегід

ПОЛ - пероксидне окиснення ліпідів

СОД - супероксиддисмутаза

СПП - сумаційно-пороговий показник

ТБК (TBA)- тіобарбітурова кислота (tiobarbiture acid)

ТБК-АП - ТБК-активні продукти

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