Pathophysiological mechanisms of hepatic immune reactivity in prolonged experimental exposure of the body to sodium fluoride

Author(s):  
А.С. Казицкая ◽  
Т.К. Ядыкина ◽  
М.С. Бугаева ◽  
А.Г. Жукова ◽  
Н.Н. Михайлова ◽  
...  

В условиях непрерывного воздействия неблагоприятных факторов окружающей и производственной среды на человека особую актуальность приобретает изучение механизмов, поддерживающих гомеостаз организма. Длительное поступление фторидов в организм приводит к формированию хронической фтористой интоксикации, патогенез которой вызывает многочисленные споры и дискуссии. До сих пор недостаточно внимания уделяется изучению висцеральной патологии, обусловленной нарушениями иммунного статуса в условиях воздействия на организм соединений фтора. Практически отсутствуют исследования по изучению иммунной реактивности, определяющей морфофункциональный характер ответной реакции печени на ранних стадиях развития фтористой интоксикации. Цель работы - изучение действий патофизиологических механизмов иммунной реактивности печени при субхроническом действии на организм соединений фтора. Методика. Опыты проведены на 210 лабораторных крысах-самцах массой 180-220 г., разделенных на 2 группы: контрольную (n=80) и группу животных с субхроническим действием фторида натрия (n=130). Экспериментальные животные в течение 12 нед имели свободный доступ к водному раствору фторида натрия (концентрация 10 мг/л, что составляет суточную дозу фтора 1,2 мг/кг массы тела). Для изучения иммунологических и биохимических показателей забирали кровь из хвостовой вены через 1, 3, 6, 9, 12 нед от начала эксперимента. Для оценки состояния гуморального звена иммунитета определяли уровень сывороточных иммуноглобулинов (IgA, IgG, IgM) иммуноферментным анализом с помощью наборов реактивов ЗАО «Вектор-Бест» (Новосибирск). Уровень сывороточных цитокинов: TNF-α, IL-1β, 2, 4, 6, 10 определяли на анализаторе Multiskan EX методом иммуноферментного анализа с использованием наборов «Вектор Бест» (Новосибирск). Подсчет общего количества лейкоцитов произведен классическим способом в камере Горяева, анализ лейкоцитарной формулы - в окрашенных мазках периферической крови. Метаболические изменения оценивали по активности ферментов в ткани печени: щелочной фосфатазы (ЩФ), аланин- и аспартатаминотрансфераз (АЛТ, АСТ), лактатдегидрогеназы (ЛДГ), гаммаглутамилтранспептидазы (γ-ГТ). Активность ферментов определяли унифицированными методами с помощью наборов реактивов ЗАО «Вектор-Бест» (Новосибирск) на фотометре PM-750 (Германия). Гистологические исследования печени осуществляли после декапитации крыс, проводимой под эфирным наркозом. Результаты. Показано, что субхроническое воздействие фторида натрия сопровождается формированием внутриклеточных и внутрисосудистых повреждений печени. Активация медиаторов воспаления и развитие иммунологических нарушений в динамике эксперимента способствуют формированию системной воспалительной реакции, которая приводит к появлению стойких морфологических нарушений в печени и изменению активности ферментов основных метаболических путей. Заключение. Полученные результаты могут быть использованы при разработке и проведении профилактических мероприятий в условиях воздействия на организм высоких концентраций фтора с последовательным применением детоксикационной, иммуномодуляторной и органопротекторной коррекции. Studying mechanisms, which maintain the body homeostasis, is particularly important in the conditions of continuous impact of adverse environmental and manufacturing factors. Long-term exposure to fluorides leads to chronic fluoric intoxication, the pathogenesis of which is a subject of multiple controversy and discussions. Not enough attention is still paid to elucidating the visceral pathology associated with fluorine-induced immune disorders. There are virtually no studies of immune reactions that define the morphofunctional nature of the liver response to early stages of fluoric intoxication. Aim. To study pathophysiological mechanisms of hepatic immune reactivity in subchronic exposure of the body to fluorine compounds. Methods. Experiments were performed on 210 male rats weighing 180-220 g. The animals were divided into two groups: 1) control (n=80) and 2) subchronic exposure to sodium fluoride (n=130). The rats had free access to a 10 mg/l aqueous solution of sodium fluoride (daily dose, 1.2 mg/kg body weight) for 12 weeks. Blood was withdrawn from the caudal vein at 1, 3, 6, 9, and 12 weeks of the experiment for immunological and biochemical tests. Histological study of the liver was performed after decapitation of rats under ether anesthesia. Results. The subchronic exposure to sodium fluoride was associated with intracellular and intravascular damage of the liver. Activation of inflammatory mediators and development of immunological disorders during the experiment contributed to a systemic inflammatory reaction, which resulted in persistent morphological injuries of the liver and changes in enzyme activities in major metabolic pathways. Conclusion. The study results can be used for development and implementation of preventive measures against the effects of high fluorine concentrations, which would include a successive use of detoxification, immunomodulation and organ protection.

Author(s):  
O. M. Kopanytsia ◽  
M. I. Marushchak ◽  
A. A. Shcherbatyy

Introduction. In the scientific literature there is a large number of publications on the chemical modification of carrageenans, the relationship between the chemical structure and their biological activity, and new opportunities for their usage in medicine. That is whyit is modern to study the properties and the state of organs and systems of the body in case of carrageenan intake.The aim of the study – to learn the indices of metabolic processes in the wall of the small intestine, myocardium and liver of experimental animals using 1% carrageenan solution.Research Methods. The study was carried out on 24 white non-linear male rats. The animals of the experimental group were provided with free access to a 1.0% of carrageenan solution for 1 month. In the selected samples of the small intestine, heart and liver was evaluated the intensity of the processes of lipid peroxidation by the content of hydroperoxides and TBA-active products.Results and Discussion. It was found that the intake of a 1% solution of κ-carrageenan led to activation of lipid peroxidation both in the wall of the small intestine and in the tissues of the liver and myocardium, however, their intensity was different. The lipoperoxidation activity was highest in the small intestine wall, while the hydroperoxides and TBA-active products were less in the myocardial tissues. So, the oral usage of carrageenan in the form of a 1% water solution has a direct and indirect damaging effect on the free radical processes in the body.Conclusions. Oral administration of a 1% carrageenan solution in experimental animals leads to statistically significant activation of free radical oxidation processes in the small intestine wall, heart and liver tissues, characterized by an increase in the content of both primary and secondary products of lipoperoxidation (p<0.05).


2020 ◽  
Vol 70 (2) ◽  
pp. 144-151
Author(s):  
María del Rocío Padilla Galindo ◽  
Alma Gabriela Martínez Moreno ◽  
Fatima Ezzahra Housni ◽  
Zyanya Reyes Castillo ◽  
Erika Saenz-Pardo Reyes

El consumo de stevia ha sido promovido por su bajo aporte calórico, su efecto antidiabético y antihipercolesterolémico. Sin embargo, los efectos de la ingesta de stevia parecen no ser los mismos para las ratas hembras respecto de los machos. El propósito de este estudio fue evaluar el efecto de la ingesta de stevia sobre el consumo de alimento, peso corporal y niveles de glucosa, insulina, colesterol y triglicéridos en ratas hembras Wistar durante 13 semanas y realizar un análisis predictivo del peso corporal y la ingesta de alimento a 20 semanas. Se utilizaron 20 ratas hembras adultas, que se dividieron en 2 grupos: control (CG) y stevia (SG), ambos grupos recibieron agua y comida a libre acceso, así como una solución de stevia al 0,2 % para el grupo SG. Se registró diariamente el consumo de alimento, agua y solución de stevia; la medición del peso corporal se realizó semanalmente. Al final de las 13 semanas de experimentación, los animales se sacrificaron para evaluar los parámetros metabolicos. El grupo SG mostró un mayor consumo de alimento, mayor proporción de ganancia de peso corporal, niveles de glucosa y colesterol que el grupo CG. No se encontraron diferencias significativas en los niveles de triglicéridos e insulina. Respecto al análisis predictivo (semanas 14-20), se mantiene un incremento significativo en el consumo de alimento y se observa una tendencia de aumento en la proporción de ganancia de peso corporal. Esto indica que el consumo de stevia en ratas hembras parece no tener los mismos efectos benéficos reportados en machos. Consumption of stevia has been promoted due to its low caloric intake, it’s effects as anti-diabetic and anti-hypercholesterolemic. However, the effects of stevia consumption is apparently not the same in females than males. The purpose of this study was to evaluate the effect of stevia intake on meal consumption, body weight and levels of glucose, insulin, cholesterol and triglycerides in female Wistar rats during 13 weeks and develop a predictive analysis of the body weight and meal intake over 20 weeks. 20 adult female rats were utilized, these were divided into two groups: control (CG) and stevia (SG), both groups received free access to water and food, the SG also received a stevia solution at 0.2%. Consumption of food, water and stevia solution was recorded daily, while weight was recorded weekly. At the end of the 13 weeks of experiment, the subjects were sacrificed to evaluate the metabolic parameters. The SG group showed a higher consumption of food, higher proportion of body weight gain, glucose levels and cholesterol than the CG. No significant differences were found in levels of triglyceride or insulin. Respect to the predictive analysis (weeks 14-20), a significant increase in food consumption is maintained and an increasing trend is observed in the proportion of body weight gain. This indicates that stevia consumption appears not to have the same benefit effects in female rats than male rats.


1985 ◽  
Vol 104 (3) ◽  
pp. 427-431 ◽  
Author(s):  
G. Forsberg ◽  
K. Abrahamsson ◽  
P. Södersten ◽  
P. Eneroth

ABSTRACT Rats, deprived of maternal contact and nutrition every alternate day starting on day 5 of life, attained a body weight at 45 days of age which was 50% of that of rats which had free access to maternal contact and nutrition. After 55 days of unrestricted food availability the body weight of the neonatally deprived rats was approximately 15% lower than that of the controls. Malnourished female rats showed normal behavioural oestrous cycles and became pregnant and lactated normally as young adults. After ovariectomy they showed higher lordosis quotients in response to treatment with oestradiol benzoate and progesterone than controls but lost less body weight in response to treatment with oestradiol-filled constant-release implants. Malnourished male rats ejaculated less frequently than controls in tests with sexually receptive female rats but this difference disappeared with repeated testing. The malnourished males showed longer ejaculation latencies and had somewhat higher serum concentrations of LH than controls after castration and treatment with testosterone-filled constant-release implants which reduced serum androgen concentrations to about 30% of the intact level. The results show that rats are capable of sustaining a rather severe neonatal nutritional deprivation without losing the capacity for essentially normal mating behaviour in adulthood. J. Endocr. (1985) 104, 427–431


2021 ◽  
Vol 100 (7) ◽  
pp. 693-699
Author(s):  
Tatyana K. Yadykina ◽  
Nadezhda N. Mikhailova ◽  
Maria S. Bugaeva ◽  
Larisa G. Gorokhova ◽  
Vera V. Kislitsyna ◽  
...  

Introduction. Aluminium production is characterized by the accumulation of impurities of various toxic and chemical compositions in the air of working areas, the predominant among which are fluoride compounds. The accumulation of fluorides in the body causes the development of osteoarticular and associated systemic pathology. The aim of the study was to evaluate the hygienic and medico-biological features of toxic liver damage in the conditions of chronic fluoride intoxication of the body. Material and methods. The hygienic working conditions of the workers of the primary professions in aluminium production were evaluated. The analysis of hepatobiliary dysfunction based on clinical and instrumental methods was carried out in 263 subjects with fluoride intoxication and a comparison group of 116 persons. Experimental studies of the morpho-functional liver state in modelling chronic fluoride intoxication were carried out based on toxicological, biochemical, pathomorphological methods with histological analysis of tissues. The toxic properties of sodium fluoride were studied in 117 white laboratory male rats with its peroral route intake into the body. Results. The qualitative composition of the air in the working areas in the electrolysis building was analyzed. The prevalence of pathological disorders of the biliary tract in metallurgists engaged in aluminium production was assessed. Clinical studies revealed a significant prevalence of toxic fluoride hepatopathy, fatty hepatosis, cholecystitis and other disorders in the group of patients with chronic fluoride intoxication. The harmful effect of sodium fluoride on hepatocytes, vessels of the portal tract was shown in an experiment. Hyperfunction of the reticuloendothelial system, Kupffer cell proliferation, irreversible destruction of hepatocytes, necrosis against the background of severe dystrophy, and decreased synthetic activity of the liver were determined. Conclusion. The structure of occupational diseases in the workers engaged in the aluminium production is dominated by hepatobiliary pathology caused by toxic liver damage with fluoride confirmed by experimental data on destructive violations of its morphostructure.


2019 ◽  
Vol 11 (2) ◽  
pp. 211-217
Author(s):  
Fitmawati Fitmawati ◽  
Agus Saputra ◽  
Titrawani Titrawani ◽  
Erwina Juliantari ◽  
Awal Prichatin Kusumo

Obat Pahit from Lingga Malay ethnic is a traditional medicine which has believed by the local people to maintain the body stamina (immunomodulators and antioxidants). This study aimed to investigate the effect of Obat Pahit Potion on kidney histological structure of white male rats (Rattus norvegicus). This research was an experimental study with a Randomized Complete Block Design consisted of 15 treatments and 3 replications. The experiment groups consisted of control groups (Stimuno, distilled water, and CMC-Na 1%) and three treatment groups of Obat Pahit Potion (Kalan, SP4, Linau) with 4 different dosages. The samples of a kidney of white rats were prepared for histological observation using paraffin method and Hematoxylin-Eosin staining. The results of this study showed that three kinds of Obat Pahit with four different dosages showed the expansion of glomerular cells on kidney tissue. Damage that occurs in the kidneys is still in small amounts and normal range which is less than 25%. The results of this study provide information for the society that the consumption of Obat Pahit Potion will not cause toxicity effect on the kidney.


1961 ◽  
Vol 201 (2) ◽  
pp. 329-333 ◽  
Author(s):  
Ashton B. Morrison

Inulin space and thiocyanate space determinations were made on three groups of male rats: the first group was chronically undernourished by feeding a restricted ration for 10 weeks, the second group was starved with free access to water, and the third was made up of normal male controls. The inulin space was found to expand relative to the final body weight or lean body mass in the undernourished animal. No absolute increase in inulin space took place. In starvation the inulin space did not change in proportion to the body weight and its absolute value decreased. The thiocyanate space relative to the final body weight or lean body mass expanded slightly but significantly in chronic undernutrition and in starvation, but no absolute increase of the thiocyanate space took place.


2008 ◽  
Vol 31 (4) ◽  
pp. 6
Author(s):  
A-M Carreau ◽  
H Patural ◽  
A Doueik ◽  
P-H Fortier ◽  
J P Praud

Background: Daily clinical observations and a recent study (D Vermeylen et al., 2004) suggest that reflux laryngitis (RL) is involved in apneas/ bradycardias of the newborn. The aim of this study is to develop and tovalidate a unique RL model in newborn lambs to test the assumption that a RL provokesan increase in apneas/ bradycardias/ desaturations observed within thelaryngeal chemoreflexes induced by the contact of a liquid with the larynx. Methods: A surgical instrumentation was performed on the first day of life, which included the insertion of a transcutaneous esophageal catheter in order to allow instillation of a gastric juice surrogate (HCl +pepsin at pH 2) directly on the larynx. The 2 ml-instillations were made 3 times per day for 6 consecutive days. At day 9-10 laryngeal chemoreflexes were induced during sleep. The larynx was removed at the time of necropsy to grade inflammation by a histological study. Results: Lambs in which a RL was induced (n = 4) presented characteristic signs of RL: cough, weak bleat, reduction in weight gain. Preliminary histological analyses showed a characteristic laryngeal inflammation. Preliminary results showing that apneas and oxygen desaturations seem more prominent in RL lambs than controls provided further validation ofour RL model. Conclusion: The ovine model developed in this study presents theclinical and histological characteristics of RL observed in newborns. Preliminary results suggesting that a RL increases apneas/bradycardias/desaturations when a liquid is in contact with laryngealmucosa in the newborn must be confirmed. Supported by: CIHR, FRSQ, Foundation of stars.


Author(s):  
M. S. Bugaeva ◽  
O. I. Bondarev ◽  
N. N. Mikhailova ◽  
L. G. Gorokhova

Introduction. The impact on the body of such factors of the production environment as coal-rock dust and fluorine compounds leads to certain shift s in strict indicators of homeostasis at the system level. Maintaining the relative constancy of the internal environment of the body is provided by the functional consistency of all organs and systems, the leading of which is the liver. Organ repair plays a crucial role in restoring the structure of genetic material and maintaining normal cell viability. When this mechanism is damaged, the compensatory capabilities of the organ are disrupted, homeostasis is disrupted at the cellular and organizational levels, and the development of the main pathological processes is noted.The aim of the study is to compare the morphological mechanisms of maintaining structural homeostasis of the liver in the dynamics of the impact on the body of coal-rock dust and sodium fluoride.Materials and methods. Experimental studies were conducted on adult white male laboratory rats. Features of morphological mechanisms for maintaining structural homeostasis of the liver in the dynamics of exposure to coal-rock dust and sodium fluoride were studied on experimental models of pneumoconiosis and fluoride intoxication. For histological examination in experimental animals, liver sampling was performed after 1, 3, 6, 9, 12 weeks of the experiment.Results. The specificity of morphological changes in the liver depending on the harmful production factor was revealed. It is shown that chronic exposure to coal-rock dust and sodium fluoride is characterized by the development of similar morphological changes in the liver and its vessels from the predominance of the initial compensatory-adaptive to pronounced violations of the stromal and parenchymal components. Long-term inhalation of coal-rock dust at 1–3 weeks of seeding triggers adaptive mechanisms in the liver in the form of increased functional activity of cells, formation of double-core hepatocytes, activation of immunocompetent cells and endotheliocytes, ensuring the preservation of the parenchyma and the general morphostructure of the organ until the 12th week of the experiment. Exposure to sodium fluoride leads to early disruption of liver compensatory mechanisms and the development of dystrophic changes in the parenchyma with the formation of necrosis foci as early as the 6th week of the experiment.Conclusions. The study of mechanisms for compensating the liver structure in conditions of long-term exposure to coal-rock dust and sodium fluoride, as well as processes that indicate their failure, and the timing of their occurrence, is of theoretical and practical importance for developing recommendations for the timely prevention and correction of pathological conditions developing in employees of the aluminum and coal industry.The authors declare no conflict of interests.


Author(s):  
L. B. Zavaliy ◽  
A. Yu. Simonova ◽  
M. M. Potskhveriya ◽  
Yu. N. Ostapenko ◽  
M. G. Gadzhieva ◽  
...  

Cases of thallium poisonings are regularly reported in media. In the present work, the world experience in diagnostics and treatment of victims with thallium poisoning has been compiled and summarized, search for clinical guidelines for the diagnostics, treatment and rehabilitation of patients has been carried out. The toxicokinetics and toxicodynamics, as well as pathophysiological mechanisms of thallium influence on the body are described in detail. Toxic and lethal concentrations of poison in biological media, as well as its tropicity to various tissues and body systems were determined. The clinical picture depending on the timing of poisoning and the dose of poison is described in detail. Difficulties of the differential diagnosis are defined. The most interesting cases of criminal and household poisonings with various terms of establishment of the diagnosis, doses of poisoning and outcomes are presented.


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