CORRECTION OF PATHOLOGICAL CHANGES IN SALIVARY GLANDS OF ANIMALS WITH PACLITAXEL-INDUCED NEUROPATHY.

BACKGROUND: Paclitaxel is a highly effective chemotherapeutic agent used to treat breast, ovarian, and other cancers. At the same time, paclitaxel causes peripheral neuropathy as a side effect in 45%-70% of patients. AIM: The aim of the study was to investigate the effect of paclitaxel-induced peripheral neuropathy on the development of pathological changes in the salivary glands of animals and to explore the possibility of correction of the identified changes with vitamin B/ATP complex. MATERIALS AND METHODS: To simulate toxic neuropathy, animals were injected i/p with paclitaxel 2 mg/kg for 4 days. In order to correct the identified changes, rats were injected i/m with vitamin B/ATP complex (1 mg/ kg) for 9 days. In the homogenate of the submandibular salivary glands, α-amylase activity, total proteolytic activity, total antitryptic activity, the content of medium mass molecules, thiobarbituric acid reactive substances (TBARS), oxidatively modified proteins, and catalase activity were determined. RESULTS: A significant increase in the content of oxidatively modified proteins, medium mass molecules, and the content of TBARS and significant decrease in the activity of catalase and amylase were determined in the salivary glands of animals with toxic neuropathy compared to these parameters in intact animals. Administration of vitamin B/ATP complex for 9 days against the background of paclitaxel-induced neuropathy led to normalization of antitryptic activity and amylase activity, a significant decrease in the content of oxidatively modified proteins, medium mass molecules, and TBARS along with a significant increase in catalase activity in the salivary glands of animals compared to the untreated rats with neuropathy. CONCLUSION: Paclitaxel-induced neuropathy caused the development of pathological changes in the salivary glands of rats, which was evidenced by a carbonyl- oxidative stress and impaired protein synthetic function. The correction with vitamin B/ATP complex restored the protein-synthetic function and the proteinase-inhibitor balance, suppressed the oxidative stress and normalized free radical processes in the salivary glands of rats.

[THE INFLUENCE OF MELANIN ON THE GASTRIC MUCOSA AND HYPOTHALAMIC-PITUITARY-ADRENOCORTICAL AXIS UNDER ACUTE STRESS CONDITIONS].

We studied the influence of melanin from yeast-like fungi Nadsoniella nigra strain X1 on the changes of the levels of adrenocorticotropic hormone (ACTH) and cortisol in blood serum of rats, adrenal glands weight ratio and lesions of the gastric mucosa (GM) caused by neuromuscular tension by Selye. Melanin administration restored functioning of the hypothalamic-pituitary-adrenal axis that was evident by an increase of ACTH concentration by 42% and a decrease of cortisol concentration by 19% compared to the rats injected with water (group 2). In rats treated with melanin, the adrenal glands weight ratio, didn't differ from intact control group of the rats. Melanin decreased ulcers area by 64% and reduced the content of free hydroxyproline by 29%, the free fucose by 16% and the free hexuronic acids by 24% in the GM compared to the group 2 of the rats. It is established that the mechanism of melanin stress-protective properties are based on its regulation of the glucocorticoids secretion and prevention of GM collagen and extracellular matrix substances depolymerization. Melanin possesses gastroprotective properties and is a perspective agent for preventing and treatment of consequences of the stress influence on the organism.

[Oxidative stress development in the tissues of salivary glands of rats in conditions of monosodium glutamate-induced obesity].

Pathogenic mechanisms of damage of salivary glands under obesity are an insufficiently studied problem of modem medicine. On experimental model of obesity induced by monosodium glutamate, free-radical processes and antioxidant defense system were studied in the tissues of salivary glands of rats. Under experimental obesity induced by monosodium glutamate there is a significant increase of the content of thio-barbituric acid reactive substances and a significant decrease in the activity of superoxide dismutase and catalase. Thus, it indicates to the misbalance of prooxidant and antioxidant systems and the development of oxidative stress.

Experimental correction of metabolic changes in mouth at long-term hypoacidity by multiprobiotic "Symbiter acidophilic".

It is known, that long decrease in gastric secretion leads to the development of hypergastrinemia, dysbiosis and to pathological changes in digestive organs. Very important there is a search of ways to correction of these undesirable consequences. Long-term usage of omeprazole leads to metabolic disorders in periodontium tissues and salivary glands, such as development of NO-ergic system disbalance and activation of free-radical oxidation, that are positively corrected by multiprobiotic of new generation "Symbiter acidophilic".

[Prophylactic effect of probiotic strains Bifidobacterium animalis VKL and VKB on stress-induced lesions in the gastric mucosa of rats].

It was investigated the effect of probiotic strains Bifidobacterium animalis VKL and VKB and their mixture on erosive and ulcerative lesions in the gastric mucosa (GM) of rats induced by water immersion restraint stress. It was found that separate prophylactic introduction for 14 days of Bifidobacterium animalis VKL or Bifidobacterium animalis VKB didn't protect the GM from erosive and ulcerative lesions induced by stress. Contrary prophylactic introduction of Bifidobacterium animalis VKL and VKB mixture has been effective in protecting the GM from the lesions. One of the mechanisms of the gastroprotection of these probiotic strains is prevention of mucus barrier from degradation, which was evident in decrease of free fucose and hexuronic acids content. These results confirm the expediency ofprobiotics use for the prevention of stress-induced lesions in the GM.

[Changes of NO-ergic activity in the salivary glands of rats under conditions of omeprazole-induced hypergastrinemia].

Under conditions of omeprazole-induced hypergastrinemia the activity of NOS and the concentration of NO2-, the end product of metabolism of nitric oxide were studied in salivary glands of rats. We detected an increase in NOS activity, reaching a maximum (7.61+/-0.39 Mmol [NO2-]/(g*min) at 14th day of the experiment. At 28th day following omeprazole introduction its activity was 5,76+/-0.25 Mmol [NO2-]/(g*min).

[Effect of acidophilic multiprobiotic symbiter on pathological changes in bone periodontal tissue under hypo-acidic condition].

The omeprazole-induced hypoacidity leads to metabolic disorders in the bone periodontal tissue: a disbalance of NO-ergic system, activation of collagen and noncollagen proteins catabolism. We have shown that such disorders are corrected by a multiprobiotic of new generation -- symbiter acidophilic.

Chronic stress impairs structural organization of organic matrix in bone tissue of rat periodontium.

Chronic stress promoted disintegration of collagen and non-collagen proteins in the periodontal bone tissue, which depended on typological characteristics of animals. Stress-predisposed animals were characterized by most pronounced disturbances.

[Metabolic changes in salivary glands with concurrent stomach ulcer and their correction by L-arginine]. / Metabolichni zminy v slynnykh zalozakh za peptychnoï virazky shlunka ta ïkh korektsiia L-arhininom.

On the model of peptic ulcer the mechanisms of interrelations between salivary glands and stomach have been proved. Activation of proteolysis which took place together with a decrease in the activity of alpha 1--inhibitor for proteases in lipid peroxidation (LPO), and an increase in depolymerization of glycoproteins contributed much to that pathology. The most pronounced metabolic changes in the tissues of the salivary glands were observed in stress resistant animals. The preliminary administration of NO donor L-arginin prevented an activation of proteolysis and LPO intensity. It attenuated the pathogenic influence of the factors which induced the metabolic changes in salivary glands at peptic ulcer of the stomach.

Stress-protective effect of glutapyrone belonging to a new type of amino acid-containing 1,4-dihydropyridines on periodontal tissues and stomach in rats with different resistance to stress.

Glutapyrone belonging to a new type of amino acid-containing 1,4-dihydropyridines produced a protective effect on periodontal tissues and gastric mucosa in rats with different resistance to stress during acute emotional and pain stress.

[The pathogenetic mechanisms of the correlation of stress damage to the periodontium and the stomach]. / Patohenetychni mekhanizmy koreliatsiï stresornoho poshkodzhennia parodonta ta shlunka.

Using the model of immobilizing stress it has been established the correlation of changes of proteolytic enzymes, the level of neuramin acid and the structural violations of parodontium and stomach. There was made a conclusion about high sensitivity of both parts of digestive system to stress factors which realise their parallel damage.

[The dependence of the connective tissue reaction to stress on typological body characteristics]. / Zavisimost' reaktsii soedinitel'noi tkani na stress ot tipologicheskikh svoistv organizma.

The experiment on 52 Wistar rats was made to study dependence of connective tissue reactions on typological properties of the body. The type of the reaction is closely related with the degree of changes in connective tissue structures of the digestive organs (periodontium, stomach) and the lungs. Acute stress stimulates degradation of the noncollagen proteins of the connective tissue main substance.

Simultaneous stress-induced metabolic changes in the stomach and periodontium.

Stress-induced changes in the stomach and periodontium were studied in animals with various types of nervous regulation pretreated with the regulatory peptide thymopentin. The interrelation between metabolic and structural changes in these highly sensitive to stress organs was revealed. Behaviorally active rats were most sensitive to stress. Pretreatment with thymopentin produced a stress-protective effect and attenuated stress-induced degradation of glycoproteins in digestive organs.

[The dependence of blood and tissue proteolytic activity during acute stress from A type of the organism reaction]. / Zalezhnist' proteolitychnoï aktyvnosti krovi i tkanyn pry hostromu stresi vid typu reahuvannia tvaryn.

In the experiments on rats there was grounded the dependence of proteolytic processes in tissues during acute emotional painful stress from typological peculiarities of the organism that was defined by the method of "Open field".

[The typological characteristics of the stress activation of lipid peroxidation and its correction by thymopentin]. / Typolohichni osoblyvosti stresovoï aktivatsiï perekysnoho okyslennia lipidiv ta ïkh korektsiia tymopentynom.

On the model of acute stress in rats the dependence of accumulating of peroxide hydrogen from typological peculiarities of organism was determined. The highest level of activation of lipid peroxide oxidation coincides with maximally expressed impairing of stomach mucous membrane the dependence of processes of lipid peroxide oxidation in stress from typological peculiarities of organism was grounded as well as high effectiveness of correction of ulcerogenic effects by neuropeptide thymopentin.

[The characteristics of the reactions of connective-tissue structures in acute stress]. / Osoblyvosti reaktsii spoluchnotkanynnykh struktur pry hostromu stresi.

Using the model of acute stress, it has been established that it promotes degradation of the connective tissue structures. It is testified by the elevation of collagenolytic enzymes and fucosa level in the blood serum and tissues (parodont, stomach, cornea). The degradation of connective tissues under the stress depend on the typological peculiarities of the nervous activities of the organism.

[The pathogenetic mechanisms of periodontal tissue damage in chronic stress and spontaneous periodontitis in rats]. / Patohenetychni mekhanizmy poshkodzhennia tkanyn parodontu pry khronichnomu stresi ta spontannomu parodontyti u shchuriv.

It has been found that chronic stress in rats promotes an increase in the general collagenolytic activity of the parodontium soft tissues and resorption of its osseous tissue. Analogical changes in the mentioned parameters in case of spontaneous parodontitis confirm the significant role of a chronic stress in genesis of the parodontium damage.

[Biochemical changes in mouth fluid in people with acute emotional stress exposed to natural and increased radiation]. / Izmenenie biokhimicheskikh pokazatelei, kharakternykh dlia ostrogo émotsionalnogo stressa, v rotovoi zhidkosti u liudei v usloviiakh estestvennogo i povyshennogo fonov radioaktivnosti.

Acute emotional stress in people is followed by changes in oral fluid composition (sialic acid, components of proteolytic system, lipid of peroxidation products). The possibility to use these indices for estimation of the psychoemotional stress in people is based.