scholarly journals MORPHOLOGICAL MONITORING OF EXPERIMENTAL LIVER FIBROSIS IN RATS

2021 ◽  
Vol 5 (2) ◽  
pp. 150-160
Author(s):  
V. P. Andreev ◽  
◽  
V. M. Tsyrkunov ◽  
I. A. Kondratovich ◽  
◽  
...  

Background. Though thioacetamide (TAA)-induced liver fibrosis (LF) is recognized as a classical model of toxic liver damage, there is no literature data on the description of its successive stages of histological and ultrastructural changes in various cell populations involved in fibrosis. Objective. To conduct morphological monitoring of fibrosis formation in the liver of rats using the TAA model of LF based on histological and ultrastructural changes in hepatocytes and perisinusoidal lipocytes (HSC). Material and methods. The experiment was carried out on 18 sexually mature male rats. LF was modeled by intraperitoneal injection of 2% TAA solution at a dose of 10 ml / kg every other day. Light microscopy of semi-thin sections of the liver was performed, as well as electron microscopy of ultrathin sections. Results. The study of semi-thin sections of rat liver tissue from the control group showed a normal architecture of the parenchyma, a large number of HSCs containing large lipid droplets ("resting" phenotype), a very small amount of cytoplasmic matrix poor in membrane organelles. In the animals that were receiving TAA for 4 weeks, a mesenchymalepithelial transition of HSCs from the "resting" type to a fibrogenic state (fibrogenic phenotype) was recorded, that was accompanied by a gradual decrease in the number of retinol-containing drops and the appearance of fibroblastlike cells (FLC) in HSCs. In the animals, that were receiving TAA for 12 weeks, the pool of fibrogenic cells in the liver increased, a mesothelial-mesenchymal transition occurred, characterized by the mesothelial cell migration deeper into the parenchyma and their acquisition of a mesenchymal phenotype. Lipid containing activated FLC were also found in fibrous tissue around the central vein. Foci of hepatic tissue destruction caused by necrosis and apoptosis of hepatocytes were much more common. Conclusions. Administration of TAA induces liver fibrosis while histological and ultrastructural monitoring of the state of hepatocytes and HSCs allows to monitor all stages of fibrosis, clarifying the mechanisms of damage to intracellular organelles and variants of hepatocyte death. This model of LF in rats can be used to test new antifibrotic drugs.

2017 ◽  
Vol 2 (2) ◽  
pp. 112-120
Author(s):  
Nazar Mohammed Shareef Mahmood ◽  
Sarkawt Hamad Ameen Hamad ◽  
Dlshad Hussein Hassan ◽  
Karwan Ismael Othman

The toxicity of lead acetate (L. A.) concerned to public health disruptor due to its persistence in the environment and it has the adverse influence on the human and animal health as well. It causes physiological,biochemical, and neurological dysfunctions in humans. Histologically it has a negative effect on the liver which is considered one of the major target organs where acts as detoxification machine by elimination the toxic substance from the blood in rich with it.  As well as it affects kidneys that are the two of the most filtering organs. Therefore the present study was aimed to investigate the histopathological effect of L.A. on liver and kidney tissues in male rats. Twenty male rats involved in the study were equally and randomly divided into two groups each of them involved 10 animals. Group I (castrated rats) and Group II (control) each group received 80mg/L of lead acetate dissolved in one liter distilled water by drinking for 15 days. Histological sections showed some alterations including abnormal architecture, cell degeneration, nuclear degeneration, hyperchromatic hepatocytes, immune cells, degeneration in tubules, dilation in sinusoids, dilation in central vein of liver increased bowman's space glomerular atrophy degeneration of tubular cells in liver and kidney tissues of rats in castrated rats from control group. But the size of degenerated tissue was more severe in castrated male rats. It was concluded that the castration process could produce a hypogonadism and decreased testosterone which owns many receptors in kidney and liver may produce adverse influence with L.A. administration.


2021 ◽  
Vol 20 (2) ◽  
pp. 104-108
Author(s):  
Yuri N. Korolev ◽  
Lyudmila A. Nikulina ◽  
Lyubov V. Mikhailik

The action effects of the low-intensity low-frequency magnetic field (LMF) are mainly studied in its therapeutic use and to a much lesser extent in the mode of primary prevention. Aim. To identify adaptive metabolic and ultrastructural changes in the testes of rats under the preventive action of LMF under radiation conditions. Material and methods. The experiments were carried out on 28 mature non-linear male rats weighing 180-200 g. the animals were divided into 3 groups: in the experimental group, the animals received a course of LMF procedures followed by radiation exposure; in the control group, the animals were subjected only to radiation exposure; in the intact group, the animals were not exposed to any effects. The animals were slaughtered the day after the radiation exposure. the research methods were used: biochemical (to determine the content of RNA, DNA, antioxidant activity of the testes), light – optical (to count the number of convoluted seminiferous tubule – CST, exfoliated cells, spermatogonia, to determine the index of spermatogenesis); transmission electron microscopy; morphometric analysis of mitochondria (number, average and total area). Results. The preventive effect of LMF enhanced the adaptive capabilities of the body and increased the resistance of the testes to the effects of radiation. This was manifested in an increase in the power of the antioxidant system, activation oof the cellular and intracellular regeneration processes, and a decrease in the permeability of the structures of the CST’s own shell. Conclusion. The obtained data substantiate the possibility of using LMF as a means of protecting the organs of the reproductive system in the complex prevention of the body under the influence of radiation.


2019 ◽  
Vol 25 (3) ◽  
pp. 21-26
Author(s):  
Ye.V. Shaprynskyi

Scar strictures that lead to obstruction of the esophagus do not tend to decrease lately, but on the contrary, the number of such patients is increasing, which is caused by the use of a large range of chemicals in human life. The results of treatment of scarring strictures depend on the degree of stenosis. With complete obstruction of the esophagus, the question arises about conducting surgical treatment. Methods of correction of esophageal strictures have a considerable number of postoperative complications and lethal consequences – from 5.0 % to 15.0 %. Therefore, in order to create a unified pathogenetic tactic for the management and treatment of esophageal strictures, we were offered to study the ultrastructural changes of the mucous membrane of the stricture of the second stage during its modeling in the experiment. The purpose of the work is to investigate the dynamics of ultrastructural changes of the mucous membrane of the esophagus wall in the normal and second stage of its stricture. The experimental study was performed on adult white male rats weighing between 250 and 300 g. A total of 16 animals were operated on, which were divided into 2 groups: a control group (6 rats) and a study group (10 rats). The studies were performed under ketamine anesthesia. In animals of the control group performed only laparotomy, followed by layer-by-layer suturing of the anterior abdominal wall. In animals of the study group created a model of obstruction of the esophagus of the second stage. Electron microscopic examination was performed on days 3, 4, and 5 of the experiment, eliminating animals by overdosing on ketamine. As a result of the electron microscopic study of the ultrastructural organization of basal, spinosum, superficial epitheliocytes of stratified squamous epithelium without keratin, smooth muscle myocytes of the muscular plate and contractile elements of the muscular layer of the esophagus of rats with simulated stricture of the second degree revealed dystrophic and destructive disorders that varied in depth and severity. It was established that mitochondrial dysfunction leads to a decrease in the activity of reparative, metabolic and synthetic processes of the cell, which is indirectly manifested by a decrease in ribosomes and polysomes in the cytoplasm, loosening and focal lysis of membranes of the granular endoplasmic reticulum. Stricture of esophagus of the second stage causes activation of catabolic intracellular processes in all cells, which is morphologically confirmed by the appearance in the cytoplasm of secondary lysosomes and inclusions of lipids.


Author(s):  
Yu. V. Halahan ◽  
O. Ye. Маievskyi ◽  
Yu. Y. Guminskyi ◽  
A. P. Korol ◽  
S. V. Prokopenko

Disruption of the metabolism of the essential amino acid methionine causes the syndrome of hyperhomocysteinemia. This pathological condition is associated with the risk of developing a number of diseases, including chronic liver disease. The mechanisms of liver tissue damage in hyperhomocysteinemia remain poorly understood and require more detailed study. The aim of the study is to establish the features of submicroscopic changes in the liver structure of old rats with hyperhomocysteinemia. The experimental study was performed on 22 white nonlinear old (24-26 months) male rats, which were divided into a control group and an experimental group. A model of persistent hyperhomocysteinemia was created by administering to rats of experimental group of thiolactone homocysteine at a dose of 200 mg/kg body weight intragastrically for 60 days. The study of ultrastructural changes in the lungs of rats was performed using an electron microscope PEM-125K. At experimental hyperhomocysteinemia in a liver of old rats there are changes in all structural components. Mitochondrial destruction and edema were observed in the vascular endothelium. Organelles have an enlightened matrix, a reduced number of cristae. A significant content of destructively altered mitochondria in endothelial cells indicates a failure of adaptation mechanisms. Erythrocyte sludges are observed in the lumens of the sinusoids. The number of fat-accumulating cells decreases, which indicates their transformation into fibroblasts and leads to the growth of collagen fibers, expansion of the sinusoidal spaces and the development of stromal fibrosis.


2013 ◽  
Vol 33 (1) ◽  
pp. 32-40 ◽  
Author(s):  
Y. Kalkan ◽  
Y. Tomak ◽  
D. Altuner ◽  
L. Tumkaya ◽  
H. Bostan ◽  
...  

The aim of the present study was to investigate the long-term and high-dose application of ketamine on the liver by employing histologic and biochemical methods. A total of 30 male rats were randomly assigned to control and four treatment groups ( n: 6). Saline for control group and different doses of ketamine for four treatment groups (40, 60, 80 and 100 mg kg−1) were administered intraperitoneal twice a day for 2 weeks. Immunohistological staining, light and electron microscopy were used to study tissue specimens. Histopathological changes were more severe and diverse in groups 80 and 100 mg kg−1 day−1, and the least significant change was observed in groups 40 and 60 mg kg−1 day−1. The most important ultrastructural changes were seen in mitochondria and in the rough endoplasmic reticulum. The immunoreactivity of calcineurin was determined as different. Prolonged use of ketamine caused hepatocellualar toxicity and histological changes in hepatocytes in a dose-dependent manner in all experimental groups.


2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Hanan A. Ogaly ◽  
Nadia A. Eltablawy ◽  
Reham M. Abd-Elsalam

Essential oils of some aromatic plants provide an effective nonmedicinal option to control liver fibrosis. Mentha piperita L. essential oil (MPEO) have been reported to possess protective effects against hepatotoxicity. However, its effect against liver fibrosis remains unknown. The present study investigated the antifibrogenic potential of MPEO and its underlying mechanisms. Forty male rats divided into 4 groups were used: group 1 served as normal control, group 2 (liver fibrosis) received CCl4 (2.5 mL/kg, IP, twice weekly) for 8 weeks, group 3 concurrently received CCl4 plus MPEO (50 mg/kg, IP, daily, from the 3rd week), and group 4 received MPEO only. MPOE significantly improved the liver injury markers, lipid peroxidation (LPO), antioxidant capacity, CYP2E1 gene expressionand liver histology. Furthermore, MPOE ameliorated liver fibrosis as evidenced by the reduced expression of desmin, α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), and SMAD3 proteins. In addition, MPOE counteracted the p53 upregulation induced by CCl4 at both mRNA and protein levels. In conclusion, MPOE could effectively attenuate hepatic fibrosis mainly through improving the redox status, suppressing p53 and subsequently modulating TGF-β1 and SMAD3 protein expression. These data promote the use of MPOE as a promising approach in antifibrotic therapy.


Author(s):  
Yu. V. Halahan ◽  
O. Ye. Maievskyi ◽  
Yu. Yo. Guminskyi ◽  
A. P. Korol

One of the important tasks of modern science is to find biochemical markers that would be able to reflect the risks of development and the nature of the course of various diseases, as well as to predict their possible consequences. In recent years, a significant number of compounds that can affect the biochemical profile of the organism have been identified. Homocysteine – a product of methionine metabolism, belongs to one of these markers, and the effects of its influece on the structure and function of various organs are being actively studied by modern researchers. The aim of the study is to find the patterns of electron microscopic changes in the liver structure of adult rats with hyperhomocysteinemia. The experimental study was performed on 22 white nonlinear mature male rats, which were divided into a control group and an experimental group. A model of persistent hyperhomocysteinemia was created by administering to rats of experimental group thiolactone homocysteine at a dose of 200 mg/kg body weight intragastrically for 60 days. The study of ultrastructural changes in the liver of rats was performed using an electron microscope PEM-125K. In adult rats with experimental hyperhomocysteinemia at the ultrastructural level, dystrophic and destructive changes in hepatocytes, endotheliocytes in the walls of sinusoids and Kupffer cells were found. These changes were more pronounced than in young rats with experimental hyperhomocysteinemia. Revealed structural changes in decompensation (depletion) of mitochondria – fewer number of cristae and enlightened matrix. In contrast to young rats, adult rats with hyperhomocysteinemia in the perisinusoidal spaces showed elongated Ito cells, a significant proportion of the cytoplasm is occupied by the Golgi complex and granular endoplasmic reticulum tanks, indicating protein synthesis for export. In Ito cells, the content of fat droplets, which are located on opposite poles of cells, is reduced. This morphological picture manifests the transformation of Ito cells into fibroblasts.


2020 ◽  
Vol 26 (1) ◽  
pp. 19-23
Author(s):  
Yu.V. Halahan

To date, it has been established that hyperhomocysteinemia plays a significant role in the development and progression of many diseases. The accumulation of homocysteine occurs due to a violation of the relationship between its production and excretion from the body. The liver plays an important role in the metabolism of homocysteine, because it undergoes most of the reactions of its transmethylation, and, therefore, it is the first to be adversely affected. The aim of the study is to identify the features of electron microscopic changes in the liver structure of young rats with hyperhomocysteinemia. The experimental study was performed on 22 white nonlinear young (1-2 months) male rats, which were divided into a control group and an experimental group. A model of persistent hyperhomocysteinemia was created by administering to rats the experimental group of thiolactone homocysteine at a dose of 200 mg/kg body weight intragastrically for 60 days. The study of ultrastructural changes in the liver of rats was performed using an electron microscope PEM-125K. It was found that the introduction of thiolactone homocysteine at a dose of 200 mg/kg in rats led to the development of degenerative changes in hepatocytes. Changes in the structure of liver cells manifested themselves in the form of edema of the cytoplasm and mitochondria, destruction of mitochondrial cristae, dilation of the tubules of the granular endoplasmic reticulum and tanks of the Golgi complex. The activity of fat-accumulating liver cells and stellate macrophages is characteristically. In the lumens of the sinusoidal capillaries found sweeter shaped blood elements, the cytoplasm of endothelial cells had signs of edema. Thus, in experimental hyperhomocysteinemia revealed changes at the ultrastructural level in all structural components of the liver of young rats. The identified changes are compensatory-adaptive in nature and are reversible.


Author(s):  
A. Singh ◽  
A. Dykeman ◽  
J. Jarrelf ◽  
D. C. Villeneuve

Hexachlorobenzene (HCB), a persistent and mobile organochlorine pesticide, occurs in environment. HCB has been shown to be present in human follicular fluid. An objective of the present report, which is part of a comprehensive study on reproductive toxicity of HCB, was to determine the cytologic effects of the compound on ovarian follicles in a primate model.Materials and Methods. Eight Cynomolgus monkeys were housed under controlled conditions at Animal facility of Health and Welfare, Ottawa. Animals were orally administered gelatin capsules containing HCB mixed with glucose in daily dosages of 0.0 or 10 mg/kg b.w. for 90 days; the former was the control group. On the menstrual period following completion of dosing, the monkeys underwent an induction cycle of superovulation. At necropsy, one-half of an ovary from each animal was diced into ca. 2- to 3-mm cubed specimens that were fixed by immersion in 2.5% glutaraldehyde in 0.1 M cacodylate buffer (pH 7.3). Subsequent procedures followed to obtain thin sections that were examined in a Hitachi H-7000 electron microscope have been described earlier.


Author(s):  
R.H.M. Cross ◽  
C.E.J. Botha ◽  
A.K. Cowan ◽  
B.J. Hartley

Senescence is an ordered degenerative process leading to death of individual cells, organs and organisms. The detection of a conditional lethal mutant (achloroplastic) of Hordeum vulgare has enabled us to investigate ultrastructural changes occurring in leaf tissue during foliar senescence.Examination of the tonoplast structure in six and 14 day-old mutant tissue revealed a progressive degeneration and disappearance of the membrane, apparently starting by day six in the vicinity of the mitochondria associated with the degenerating proplastid (Fig. 1.) where neither of the plastid membrane leaflets is evident (arrows, Fig. 1.). At this stage there was evidence that the mitochondrial membranes were undergoing retrogressive changes, coupled with disorganization of cristae (Fig. 2.). Proplastids (P) lack definitive prolamellar bodies. The cytoplasmic matrix is largely agranular, with few endoplasmic reticulum (ER) cisternae or polyribosomal aggregates. Interestingly, large numbers of actively-budding dictysomes, associated with pinocytotic vesicles, were observed in close proximity to the plasmalemma of mesophyll cells (Fig. 3.). By day 14 however, mesophyll cells showed almost complete breakdown of subcellular organelle structure (Fig. 4.), and further evidence for the breakdown of the tonoplast. The final stage of senescence is characterized by the solubilization of the cell wall due to expression and activity of polygalacturonase and/or cellulose. The presence of dictyosomes with associated pinocytotic vesicles formed from the mature face, in close proximity to both the plasmalemma and the cell wall, would appear to support the model proposed by Christopherson for the secretion of cellulase. This pathway of synthesis is typical for secretory glycoproteins.


Sign in / Sign up

Export Citation Format

Share Document