REACTIVE CHANGES OF LIVER AND KIDNEY HISTOLOGICAL ELEMENTS IN MURINE MODELS OF SEPSIS CAUSED BY ADMINISTRATION OF DIFFERENT STRAINS TO MICE

2020 ◽  
pp. 66-71
Author(s):  
Татьяна Геннадьевна Боровая ◽  
Владимир Григорьевич Жуховицкий ◽  
Мария Николаевна Черкасова

Цель - выявление реактивных изменений гистологических элементов печени и почек у мышей в экспериментальных моделях сепсиса, вызванного штаммами 1840 и 1623 Pseudomonas aeruginosa (PsA1840, 1623). Материал и методы. Сепсис моделировали на двух группах половозрелых самцов мышей линии C57Bl/6 интраперитонеальным введением Pseudomonas aeruginosa. Животным 1-й группы (8 особей) вводили штамм 1840, животным 2-й группы (12 особей) - штамм 1623. Контрольная группа состояла из 3 животных. Перед началом опыта штаммы тестировали на присутствие генов экзотоксинов U, S, T, Y (ExoU, ExoS, ExoT, ExoY) с помощью полимеразной цепной реакции (ПЦР). Для визуализации продуктов ПЦР применяли электрофорез в горизонтальном 1,5 % агарозном геле. Животных вскрывали на терминальной стадии сепсиса. Серийные парафиновые срезы печени и почек толщиной 4 мкм окрашивали гематоксилином - эозином, анализировали особенности гистоструктуры органов и фотографировали в световом микроскопе «AxioPlus» (фирма Zeiss, Германия). Результаты. Штамм PsA 1840, имеющий ген exoU, вызывал выраженные деструктивные изменения пластинок гепатоцитов и замещение участков паренхимы печени гомогенным эозинофильным веществом. Присутствовали признаки стаза крови в синусоидных капиллярах, расширение и тромбоз центральных вен, немногочисленные скопления лейкоцитов. Морфологические изменения нефронов состояли в локальных деструктивных изменениях проксимальных канальцев на периферии коркового вещества почек. При введении PsA1623, имеющего ген exoS, возникали массовая гибель почечных телец и дегенерация канальцев нефронов. В печени дольковая гистоархитектура в основном сохранялась. Выводы. Предполагается связь выявленных различий в реактивных изменениях гистологических элементов печени и почек в подопытных группах с особенностями геномов штаммов PsA, использованных для моделирования сепсиса. Objective - to identify reactive changes of liver and kidney histological elements in experimental models of sepsis in mice caused by 1840 and 1623 Pseudomonas aeruginosa strains (PsA1840, 1623). Material and methods. Sepsis was modeled in two groups of mature male C57Bl/6 mice by intraperitoneal administration of Pseudomonas aeruginosa. Strain 1840 was administered to animals of the first group (n=8), animals of the second group (n=12) were administered strain 1623; the control group consisted of 3 animals. Before the experiment, the strains were tested for the presence of genes of exotoxins U, S, T, Y (ExoU, ExoS, ExoT, ExoY) using polymerase chain reaction (PCR). Electrophoresis in horizontal 1,5 % agarose gel was used to visualize PCR products. The animals were euthanized at the terminal stage of sepsis. The extracted liver and kidneys were fixed according to the generally accepted histological method, and embedded into paraffin blocks. Serial 4 μm thick sections of organs were stained with hematoxylin and eosin, analyzed and photographed using «AxioPlus» light microscope (Zeiss, Germany). Results. Strain PsA 1840, carrying the gene of exotoxin U (ExoU), caused severe destructive changes of hepatocytes plates and the replacement of the liver parenchyma with homogeneous eosinophilic substance. There were signs of blood stasis in sinusoidal capillaries, expansion and thrombosis of central veins, a few accumulations of leukocytes. Morphological changes of nephrons consisted of local destructive changes in the proximal tubules at the periphery of kidney cortical substance. After the introduction of PsA1623, carrying the gene of exotoxin S (ExoS), the massive death of renal corpuscles and degeneration of nephron tubules were registered. However, the lobular histoarchitecture in the liver remained mostly unaltered. Conclusions. It is supposed that there is a possible connection of the observed differences in reactive changes of liver and kidney histological elements in two experimental groups with genome features of PsA strains used for the sepsis modeling.

2000 ◽  
Vol 44 (1) ◽  
pp. 205-206 ◽  
Author(s):  
Takashi Yokochi ◽  
Kayou Narita ◽  
Akiko Morikawa ◽  
Kazuko Takahashi ◽  
Yutaka Kato ◽  
...  

ABSTRACT The relationship between morphological changes in Pseudomonas aeruginosa following antibiotic treatment of experimental infection in mice, susceptibility to phagocytosis, and release of endotoxin was studied. The intraperitoneal administration of P. aeruginosa with imipenem or ceftazidime into mice induced morphological changes in the cells 2 h after injection. Round P. aeruginosa cells with imipenem treatment became susceptible to phagocytosis by peritoneal cells, whereas long filamentous cells with ceftazidime treatment were hardly phagocytized by peritoneal cells. The morphological changes also affected the plasma endotoxin level in the circulation.


2020 ◽  
Vol 26 (4) ◽  
pp. 22-29
Author(s):  
O.H. Kostiuk ◽  
N.L. Hodovan ◽  
P.P. Gormash ◽  
I.V. Taran ◽  
D.I. Grebeniuk ◽  
...  

Along with a good antitumor effect, Doxorubicin has a systemic effect with damage to vital organs, in particular the heart. The lack of a unified approach to dosing and the frequency of administration of Doxorubicin in the experiment prompts the search for an optimal model of Doxorubicin cardiomyopathy. The aim of the study was to develop a method of serial administration of Doxorubicin in medium therapeutic doses in an experiment and to evaluate the cardiotoxic effect of the drug. 42 female Wistar rats were included in the study. The control group consisted of 7 intact rats. The experimental group consisted of 35 rats who received systemic chemotherapy with Doxorubicin at a dose of 5 mg/kg once a week for 5 weeks. On days 7th, 14th, 21st, 28th, 35th, the hearts of experimental animals were taken for morphological examination. Histomorphometrically determined: the diameter of cardiomyocytes (in the middle part) and the transverse diameter of their nucleus, the width of the interstitial space (endo- and perimysia). The data of histomorphological and histomorphometric examination of the myocardium testified that all animals of the experimental group had a circulatory disorder in the heart muscle at the level of hemomicrocirculation. Such changes led to cardiomyocyte hypotrophy, interstitial edema and fibrosis. During systemic chemotherapy, the animals showed marked changes in the myocardium, such as expansion of the endomysial zone, due to capillary congestion and edema, in comparison with animals of the intact group. At the end of the experiment, the animals of the experimental group retained the expansion of the endomysial zone, mainly due to interstitial fibrosis. Such changes indicate myocardial hypoxemia with damage and death of cardiomyocytes, activation of interstitial and replacement collagen formation. The obtained morphological data indicate the development of dilated cardiomyopathy in experimental animals. Serial intraperitoneal administration of Doxorubicin at a dose of 5 mg/kg once a week for 5 weeks causes morphological changes in the myocardium of experimental animals, similar to changes in the heart of people undergoing chemotherapy with this drug.


2017 ◽  
Vol 22 (4) ◽  
pp. 919-925 ◽  
Author(s):  
Seun F. Akomolafe ◽  
Ganiyu Oboh ◽  
Sunday I. Oyeleye ◽  
Tosin A. Olasehinde

Tetracarpidium conophorum leaves are used in traditional medicine for the treatment of male infertility, without considering its toxicity and side effects. In this study, we investigated the effects of T conophorum leaves on some biochemical parameters such as alanine aminotransferase, aspartate aminotransferase, bilirubin, albumin, creatinine, and uric acid. Histology of the liver and kidney were also assessed. The result revealed that the alanine aminotransferase and aspartate aminotransferase levels of the control group were not significantly different from the experimental groups. There was no significant difference in the albumin and bilirubin levels of the control and experimental groups. Similarly, the uric acid and creatinine levels of the experimental rats were not significantly different from the control. The examination of liver and kidney sections did not show any morphological changes and inflammatory cell infiltrations. These findings suggest that the leaves did not induce any pathological changes at the doses tested.


Author(s):  
Omotayo Babatunde Ilesanmi ◽  
Ridwan Abiodun Lawal

Abstract. This study was designed to investigate the hepatorenal protective effects of trévo, on cadmium-induced renal and hepatic injury in male Wistar rats. Methods. Fifteen healthy male Wistar rats were divided into three groups of five rats per group. Group I (control); group II (35mg/kg cadmium chloride (CdCl2); Group III (2 ml/kg trévo+ CdCl2. The rats were treated with trévo (2ml/kg orally) and administered CdCl2 3 hrs later. Twenty-four hours after the last administration rats were sacrificed and blood was collected via cardiac puncture and processed for hematological parameters and assessment of urea, creatinine (CREA), and uric acid (UA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin (ALB). The liver and kidney were excised and processed for markers of oxidative stress. Results intraperitoneal administration of 35 mg/kg of CdCl2 caused a significant increase in serum concentration of urea, CREA, UA, AST, ALT, while the concentration of ALB was significantly lower (P<0.0001). CdCl2 caused a significant reduction in packed cell volume, hemoglobin while the total white blood cell count, neutrophils, lymphocytes, monocytes, eosinophils, and basophils were increased. Oxidative stress was significantly pronounced in the liver and kidney of rats exposed to CdCl2 as observed in the high concentration of malondialdehyde, decreased concentration of glutathione, the activity of catalase, superoxide dismutase, and glutathione-S-transferase. Pretreatment with trévo was able to significantly prevent the anemic, oxidative damage, renal and hepatic injury initiated by CdCl2. Conclusions. The study reveals that trévo is effective in attenuating cadmium-induced hepatorenal toxicity in male Wistar rats.


Author(s):  
Amanda Gubert Alves dos Santos ◽  
Maria Gabriela Lima da Silva ◽  
Erick Lincoln Carneiro ◽  
Lainy Leiny de Lima ◽  
Andrea Claudia Bekner Silva Fernandes ◽  
...  

Leishmania (Viannia) braziliensis is one of the main causes of cutaneous leishmaniasis in the Americas. This species presents genetic polymorphism that can cause destructive lesions in oral, nasal, and oropharyngeal tracts. In a previous study, the parasite caused several histopathological changes to hamster ileums. Our study evaluates immune response components, morphological changes, and effects on neurons in the ileums of hamsters infected by three different strains of L. (V.) braziliensis in two infection periods. For the experiment, we separated hamsters into four groups: a control group and three infected groups. Infected hamsters were euthanized 90- or 120-days post infection. We used three strains of L. (V.) braziliensis: the reference MHOM/BR/1975/M2903 and two strains isolated from patients who had different responses to Glucantime® treatment (MHOM/BR/2003/2314 and MHOM/BR/2000/1655). After laparotomy, ileums were collected for histological processing, biochemical analysis, and evaluation of neurons in the myenteric and submucosal plexuses of the enteric nervous system (ENS). The results demonstrated the increase of blood leukocytes after the infection. Optical microscopy analysis showed histopathological changes with inflammatory infiltrates, edemas, ganglionitis, and Leishmania amastigotes in the ileums of infected hamsters. We observed changes in the organ histoarchitecture of infected hamsters when compared to control groups, such as thicker muscular and submucosa layers, deeper and wider crypts, and taller and broader villi. The number of intraepithelial lymphocytes and TGF-β-immunoreactive cells increased in all infected groups when compared to the control groups. Mast cells increased with longer infection periods. The infection also caused remodeling of intestinal collagen and morphometry of myenteric and submucosal plexus neurons; but this effect was dependent on infection duration. Our results show that L. (V.) braziliensis infection caused time-dependent alterations in hamster ileums. This was demonstrated by the reduction of inflammatory cells and the increase of tissue regeneration factors at 120 days of infection. The infected groups demonstrated different profiles in organ histoarchitecture, migration of immune cells, and morphometry of ENS neurons. These findings suggest that the small intestine (or at least the ileum) is a target organ for L. (V.) braziliensis infection, as the infection caused changes that were dependent on duration and strain.


Author(s):  
G.A. Miranda ◽  
M.A. Arroyo ◽  
C.A. Lucio ◽  
M. Mongeotti ◽  
S.S. Poolsawat

Exposure to drugs and toxic chemicals, during late pregnancy, is a common occurrence in childbearing women. Some studies have reported that more than 90% of pregnant women use at least 1 prescription; of this, 60% used more than one. Another study indicated that 80% of the consumed drugs were not prescribed, and of this figure, 95% were “over-the-counter” drugs. Acetaminophen, the safest of all over-the-counter drugs, has been reported to induce fetal liver necrosis in man and animals and to have abortifacient and embryocidal action in mice. This study examines the degree to which acetaminophen affects the neonatal liver and kidney, when a fatty diet is simultaneously fed to the mother during late pregnancy.Timed Swiss Webster female mice were gavaged during late pregnancy (days 16-19) with fat suspended acetaminophen at a high dose, HD = 84.50 mg/kg, and a low dose, LD = 42.25 mg/kg; a control group received fat alone.


Author(s):  
А.В. Дробленков ◽  
Л.Г. Прошина ◽  
Ю.Н. Юхлина ◽  
А.А. Байрамов ◽  
П.Д. Шабанов ◽  
...  

Актуальность. Значение недостаточности тестостерона для структурного гомеостазиса нейронов, регулирующих выработку гонадотропин-рилизинг гормона (ГнРГ) и синтезирующих данный гормон, мало изучены. Цель. Установить реактивные изменения, количество рецепторов к андрогенам (АР) и особенности их распределения в нейронах медиального аркуатного ядра гипоталамуса (МАЯ) при экспериментальном гипогонадизме, а также обратимость этих изменений после восстановительной терапии тестостероном. Методы. У самцов крыс Вистар (16 особей) моделировали гипогонадизм путем удаления одной гонады на 2-3 день постнатальной жизни и исследовали гистологические срезы каудальной части МАЯ у молодых животных (4 мес.) при отсутствии и осуществлении заместительной терапии. Контрольную группу составляли интактные самцы аналогичного возраста (8 особей). В середине левосторонней части МАЯ на площади 0,01 мм определяли реактивные изменения клеток и площадь тел малоизмененных нейронов (после окрашивания срезов методом Ниссля), а также число и долю тел нервных клеток, различавшихся по степени экспрессии АР. Результаты. Установлено, что нейроны МАЯ содержат большое количество АР, распределенных в различных частях их тела. При гипогонадизме происходит перераспределение АР и снижение степени их экспрессии (количества). Сгущение АР в области оболочки ядра и плазмолеммы, образование конгломератов в ядре и цитоплазме было характерно для нейронов с умеренной экспрессией. В цитоплазме и в области плазматической мембраны рецепторы отсутствовали у клеток со слабой и очень низкой экспрессией. Снижение степени экспрессии АР при гипогонадизме сопряжено с уменьшением площади тела и гибелью части нейронов. Заключение. Выявленные дегенеративные тестостерон-зависимые изменения нейронов МАЯ, которые синтезируют ГнРГ или пептиды, влияющие на его выработку, могут обусловить уменьшение высвобождения гонадолиберина, вторичное снижение синтеза андрогенов и реализацию морфофункциональных проявлений его вторичного дефицита. Заместительная терапия частично компенсирует дегенеративные изменения нейронов, восстанавливает интенсивность экспрессии АР, однако не влияет на процесс гибели нервных клеток. Background. Importance of testosterone deficiency for structural homeostasis of the neurons regulating production of gonadotropin-releasing hormone (GnRH) and synthesizing this hormone is insufficiently understood. Aim. To determine reactive changes, quantity of androgens receptors (AR), and features of their distribution in neurons of hypothalamic medial arcuate nucleus (MAN) in experimental hypogonadism and reversibility of these changes by restorative therapy with testosterone. Methods. Hypogonadism was modeled in 16 Wistar rats by removing one gonad on postnatal days 2-3, and histological sections of caudal MAN were examined in young, 4-month old animals with and without a replacement therapy. The control group consisted of 8 age-matched intact males. Cell reactive changes, areas of slightly changed neuron bodies (Nissl staining of sections), and the number and proportion of nerve cell bodies differing in the degree of AR expression were determined in the middle left-sided part of MAN, on an area of 0.01 mm. Results. MAN neurons contained a large quantity of AR distributed in different parts of the neuron body. In hypogonadism, AR redistributed and their expression (quantity) decreased. Condensation of AR in the region of nucleo- and plasmolemma and formation of conglomerates in the nucleus and cytoplasm were characteristic of neurons with moderate expression. In the regions of cytoplasm and plasma membrane, the receptors were absent in cells with low and very low expression. The reduced AR expression in hypogonadism was associated with a decreased neuron body area and death of a part of neurons. Conclusions. The identified degenerative changes in the testosterone-dependent neuronal MAN that synthesize GnRH or peptides affecting the GnRH production may decrease the release of GnRH, cause a secondary decrease in the androgen synthesis, and mediate morphological and functional manifestations of GnRH secondary deficit. The replacement therapy partially compensated for degenerative changes in neurons and restored the intensity of AR expression, however, it did not influence the process of nerve cell death.


Author(s):  
Semeleva E.V. ◽  
Blinova E.V. ◽  
Zaborovsky A.V. ◽  
Vasilkina O.V. ◽  
Shukurov A.S.

In this work, we studied the pharmacological activity of zinc and magnesium salts of 2-aminoethanesulfonic acid in white non-linear male rats with amyotrophic lateral sclerosis, which was modeled by neurotoxicantsimplication into the pelvic part of spinal cord. After the reproduction of the pathology in animals, the indices of motor activity were recorded in the Rotarod test, and morphological studies of spinal cord sections stained according to Nisl in the Belshovsky modification were carried out. It was shown that the magnesium salt of 2-aminoethanesulfonic acid (compound LHT-317) to a greater extent reduces the development of motor disorders in experimental animals compared with the control group on the 4th day of observation. The course of intravenous administration of the studied compounds of 2-aminoethanesulfonic acid did not inhibit morphological changes in the spinal cord that develop in degenerative-dystrophic pathology of the central nervous system: connections. Moreover, if, against the background of treatment with zinc salt, the total area of motor zones in animals of the experimental group exceeded that of control rats, then the number of motoneurons did not differ from the control.


Author(s):  
Mozhgan Ghorbani ◽  
Atefeh Araghi ◽  
Nabi Shariatifar ◽  
Seyed Hooman Mirbaha ◽  
Behrokh Marzban Abbasabadi ◽  
...  

Aims: The aim of this study was to investigate the toxic effect of Echium amoenum plants on the liver and kidney of animal model. Background: Echium amoenum is one of the medicinal plants containing pyrrolizidine alkaloids with several properties which has widely consumed among different communities. Objective: The toxic effects of Echium amoenum on the liver and kidney were investigated in this study. Methods: Sixty mice were kept for 28 days under the appropriate laboratory conditions. Echium amoenum extract (25, 12.5, 50 mg / kg, ip.) was administered for 28 days. At the end of experiment, blood samples were drawn and liver and kidneys were removed for evaluating hepatotoxicity and nephrotoxicity of extract. Additionally, experiments were conducted to assay the enzymatic and oxidative activities. Results: There was no significant difference in the levels of copper ion in the liver and kidneys among all groups. There was a significant difference in the levels of lipid peroxidation in the liver of treated groups versus control group. The significant difference was not observed in the levels of glutathione of the liver of all groups. However, the levels of glutathione of the kidney significantly decreased in the treated groups versus control group. There was no significant difference in the liver enzymes including ALP, SGOT, and SGPT between all groups. This indicates that damage increase with enhancing the time and concentrations of extract. Biochemical analysis showed the creatinine and urea levels did not change in the treated groups versus control group. Conclusion: According to the present findings, it is suggested that Echium amoenum causes hepatotoxicity and nephrotoxicity effects in dose and time dependent manner.


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