scholarly journals Cardiac remodeling and MMPs on the model of chronic daunorubicin-induced cardiomyopathy in rabbits

2010 ◽  
pp. 831-836
Author(s):  
M Adamcová ◽  
A Potáčová ◽  
O Popelová ◽  
M Štěrba ◽  
Y Mazurová ◽  
...  

The matrix metalloproteinases (MMPs) play a key role during cardiac remodeling. The aim of the study was to investigate the changes in collagenous proteins and MMPs in the model of non-ischemic, anthracycline-induced chronic cardiomyopathy in rabbits using both biochemical and histological approaches. The study was carried out in three groups of Chinchilla male rabbits: 1) daunorubicin (3 mg/kg, once weekly for 10 weeks), 2) control (saline in the same schedule), 3) daunorubicin with the cardioprotectant dexrazoxane (60 mg/kg, before each daunorubicin). Morphological changes in the myocardium of daunorubicin-treated animals were characterized by focal myocardial interstitial fibrosis of different intensity. The subsequent proliferation of the fibrotic tissue was marked by an increased content of both collagen types I and III, which resulted in their typical coexpression in the majority of bundles of fibers forming either smaller or larger scars. Biochemical analysis showed a significantly increased concentration of hydroxyproline, mainly in the pepsin-insoluble fraction of collagenous proteins, in the daunorubicin-treated group (1.42±0.12 mg/g) as compared with the control (1.03±0.04 mg/g) and dexrazoxane (1.07±0.07 mg/g) groups. Dexrazoxane co-administration remarkably reduced the cardiotoxic effects of daunorubicin to the extent comparable with the controls in all evaluated parameters. Using zymography, it was possible to detect only a gelatinolytic band corresponding to MMP-2 (MMP-9 activity was not detectable). However, no significant changes in MMP-2 activity were determined between individual groups. Immunohistochemical analysis revealed increased MMP-2 expression in both cardiomyocytes and fibroblasts. Thus, this study has revealed specific alterations in the collagen network in chronic anthracycline cardiotoxicity in relationship to the expression and activity of major MMPs.

Animals ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 3430
Author(s):  
Maciej Dobrzyński ◽  
Jan P. Madej ◽  
Anna Leśków ◽  
Małgorzata Tarnowska ◽  
Jacek Majda ◽  
...  

Dioxins are chemical compounds that may cause an inflammatory reaction. During dioxin-induced inflammation, generated reactive oxygen species lead to morphological changes in various tissues and in biochemical parameters. The aim of this study was to demonstrate the changes in the livers of rats whose mothers were exposed to dioxins and the protective role of α-tocopherol and acetylsalicylic acid in liver inflammation. The study material consisted of Buffalo rats who were the offspring of females treated with dioxin, dioxin + α-tocopherol, or dioxin + acetylsalicylic acid. Livers and blood samples were taken from the rats’ offspring, and then histopathological and biochemical analyses were performed. The histopathological analysis showed that the changes observed in the livers of neonates were the result of the dioxins derived from their mother. The biochemical analysis showed that the morphological changes in the liver affected its function, which manifested in a higher total protein concentration in the dioxin-treated group, and that the creatinine level in this group was significantly higher than that in the other groups. This effect was reduced by the protective role of α-tocopherol and acetylsalicylic acid. Based on these results, we came to the conclusion that dioxins significantly affect the structure of the liver, which negatively affects its function, mainly in the scope of the metabolism of plasma proteins and hepatic enzymes.


Author(s):  
Andrea Jaquins-Gerstl ◽  
Kathryn M. Nesbitt ◽  
Adrian C. Michael

AbstractThe neurochemical transmitter dopamine (DA) is implicated in a number of diseases states, including Parkinson’s disease, schizophrenia, and drug abuse. DA terminal fields in the dorsal striatum and core region of the nucleus accumbens in the rat brain are organized as heterogeneous domains exhibiting fast and slow kinetic of DA release. The rates of dopamine release are significantly and substantially faster in the fast domains relative to the slow domains. The striatum is composed of a mosaic of spatial compartments known as the striosomes (patches) and the matrix. Extensive literature exists on the spatial organization of the patch and matrix compartments and their functions. However, little is known about these compartments as they relate to fast and slow kinetic DA domains observed by fast scan cyclic voltammetry (FSCV). Thus, we combined high spatial resolution of FSCV with detailed immunohistochemical analysis of these architectural compartments (patch and matrix) using fluorescence microscopy. Our findings demonstrated a direct correlation between patch compartments with fast domain DA kinetics and matrix compartments to slow domain DA kinetics. We also investigated the kinetic domains in two very distinct sub-regions in the striatum, the lateral dorsal striatum (LDS) and the medial dorsal striatum (MDS). The lateral dorsal striatum as opposed to the medial dorsal striatum is mainly governed by fast kinetic DA domains. These finding are highly relevant as they may hold key promise in unraveling the fast and slow kinetic DA domains and their physiological significance. Graphical abstract


1998 ◽  
Vol 111 (11) ◽  
pp. 1545-1554 ◽  
Author(s):  
A.W. Koch ◽  
T.W. Holstein ◽  
C. Mala ◽  
E. Kurz ◽  
J. Engel ◽  
...  

Here we present the cloning, expression and immunocytochemical localization of a novel 24 kDa protein, designated spinalin, which is present in the spines and operculum of Hydra nematocysts. Spinalin cDNA clones were identified by in situ hybridization to differentiating nematocytes. Sequencing of a full-length clone revealed the presence of an N-terminal signal peptide, suggesting that the mature protein is sorted via the endoplasmic reticulum to the post-Golgi vacuole in which the nematocyst is formed. The N-terminal region of spinalin (154 residues) is very rich in glycines (48 residues) and histidines (33 residues). A central region of 35 residues contains 19 glycines, occurring mainly as pairs. For both regions a polyglycine-like structure is likely and this may be stabilized by hydrogen bond-mediated chain association. Similar sequences found in loricrins, cytokeratins and avian keratins are postulated to participate in formation of supramolecular structures. Spinalin is terminated by a basic region (6 lysines out of 15 residues) and an acidic region (9 glutamates and 9 aspartates out of 32 residues). Western blot analysis with a polyclonal antibody generated against a recombinant 19 kDa fragment of spinalin showed that spinalin is localized in nematocysts. Following dissociation of the nematocyst's capsule wall with DTT, spinalin was found in the insoluble fraction containing spines and the operculum. Immunocytochemical analysis of developing nematocysts revealed that spinalin first appears in the matrix but then is transferred through the capsule wall at the end of morphogenesis to form spines on the external surface of the inverted tubule and the operculum.


1998 ◽  
Vol 275 (1) ◽  
pp. F143-F153 ◽  
Author(s):  
L. B. Zimmerhackl ◽  
F. Momm ◽  
G. Wiegele ◽  
M. Brandis

Cadmium toxicity to renal cells was investigated in Madin-Darby canine kidney (MDCK) and LLC-PK1cells as models of the distal tubule/collecting duct and proximal tubule, respectively. Cells were grown on two-compartment filters and exposed to 0.1–50 μM Cd2+. In MDCK cells, Cd2+was more toxic from the basolateral than from the apical side and dependent on the extracellular Ca2+concentration. Toxicity was evident within 24 h, as shown by a decrease in transepithelial resistance (TER), reduced proliferation (bromodeoxyuridine incorporation), reduction in ATP concentration, and morphological changes. On confocal microscopy, E-cadherin and α-catenin staining patterns indicated interference with the cadherin-catenin complex. LLC-PK1cells showed a similar toxicity pattern, which was evident at lower Cd2+concentrations. An increase of E-cadherin and α-catenin molecules in the Triton X-100-insoluble fraction was detectable at high Cd2+concentrations in LLC-PK1cells but not in MDCK cells. Lactate dehydrogenase release indicated membrane leakage in LLC-PK1cells. Rhodamine-phalloidin staining, a probe for F-actin filaments, demonstrated alterations of the actin cytoskeleton in both cell lines. In conclusion, cadmium caused ATP depletion and interfered with the cadherin-catenin complex and probably the tight junctions changing renal cell morphology and function.


2020 ◽  
Vol 16 (2) ◽  
Author(s):  
P. M. Ridzuan ◽  
Nasir Mohamad ◽  
Salwani Ismail ◽  
Nor Iza A. Rahman ◽  
Sanusi N.A ◽  
...  

Trichophyton rubrum is a common pathogenic fungal species that is responsible for causing infection on human skin, hair and nail. The antifungal-resistant strains complicate the treatment regime. Hydroxychavicol (HC) is one of the main compounds from Piper betel leaf that have antifungal potential and its mechanism of action has not been studied yet. The objective of this preliminary study to determine the antifungal properties of HC against T. rubrum using transmission electron microscope (TEM) on gross and ultrastructure of T. rubrum hypha. T. rubrum was treated with HC and miconazole (MI) at concentrations of 1.25, 2.5, 5 and 10 mg/mL for 1, 3, 5 and 7 days continuously. Generally, fungi structures became more severely damaged at increasing treatment duration. Microscopically, the fungi’s cell wall treated with HC showed a rough surface, shrinkage and demolition similar to the MI treated group. The fungi organelles were also demolished and disorganized. This study revealed that HC has the ability to inhibit T. rubrum growth and has potential to be an antifungal agent for skin infections.


1990 ◽  
Vol 96 (4) ◽  
pp. 583-590
Author(s):  
M. Veenhuis ◽  
J.M. Goodman

Peroxisomes are massively induced when methylotrophic yeasts are cultured in medium containing methanol. These organelles contain enzymes that catalyze the initial steps of methanol assimilation. In Candida boidinii, a methylotrophic yeast, the peroxisomal matrix (internal compartment) is composed almost exclusively of two proteins, alcohol oxidase and dihydroxyacetone synthase; catalase is present in much lower abundance. Monoclonal and polyclonal antibodies are available against peroxisomal matrix and membrane proteins. These were utilized to correlate the induction of specific proteins with the morphological changes occurring during peroxisomal proliferation. Cells cultured in glucose-containing medium contain two to five small microbodies, which are identifiable by catalase staining and immunoreactivity with a monoclonal antibody against PMP47, an integral peroxisomal membrane protein. Three stages of proliferation can be distinguished when cells are switched to methanol as the carbon source. (1) There is an early stage (within 1 h) in which several peroxisomes develop from a preexisting organelle. This is accompanied by an increase in catalase activity and an induction of PMP47, but no detectable induction of alcohol oxidase or dihydroxyacetone synthase is observed. (2) From 1 to 2.5 h there is further division of these microbodies until up to 30 small peroxisomes generally are present in each of one or two clusters per cell. Induction of alcohol oxidase, dihydroxyacetone synthase and PMP20, a protein that is distributed in the matrix and membrane, is detectable during this time. Serial sections reveal that some peroxisomes remain uninduced while others undergo proliferation. Such sections also show no obvious connections between peroxisomes within clusters.(ABSTRACT TRUNCATED AT 250 WORDS)


2021 ◽  
Vol 8 ◽  
Author(s):  
Hong-jin Chen ◽  
Xiao-xi Pan ◽  
Li-li-qiang Ding ◽  
Cheng-chao Ruan ◽  
Ping-jin Gao

Cardiac remodeling consisted of ventricular hypertrophy and interstitial fibrosis is the pathological process of many heart diseases. Fibroblasts as one of the major cells in the myocardium regulate the balance of the generation and degeneration of collagen, and these cells transform toward myofibroblasts in pathological state, contributing to the remodeling of the heart. Peroxisome proliferator-activated receptor-γ (PPAR-γ) coactivator-1α (PGC-1α) is vital to the function of mitochondria, which contributes to the energy production and reactive oxidative species (ROS)-scavenging activity in the heart. In this study, we found that fibroblast-specific PGC-1α KO induced cardiac remodeling especially fibrosis, and Angiotensin II (AngII) aggravated cardiac fibrosis, accompanied with a high level of oxidative stress response and inflammation.


Author(s):  
Oleksiy Tkachenko ◽  
◽  
Olena Havrylina ◽  

The active spread of respiratory infections in pig farms raises the issue of differential pathomorphological diagnosis of diseases related to a single syndrome of respiratory pathologies. Pathological autopsy and histopathological examinations of organs from 72 carcasses of pigs during the fattening period were performed. Pathological autopsy of pigs was performed by complete evisceration. Histologically examined 360 lung samples with regional lymph nodes. The presence of bacterial and viral infections was confirmed by bacteriological and PCR studies. The aim of the study is to establish the characteristic differential features at the macro- and micro-level in the lungs of domestic pigs for viral and bacterial pathogens. The main tasks of the work are to determine the morphofunctional features and dynamics of pathomorphological changes in the parenchyma and immune formations of the lungs in respiratory pathology. As a result of complex pathomorphological studies of the lungs in respiratory infections of pigs found that structural and functional changes in the body have different localization, stage and nature of the pathological process, which depend on the direct action of the etiological factor. Acute catarrhal bronchopneumonia is registered in respiratory mycoplasmosis (enzootic pneumonia), which in a prolonged course turns into chronic catarrhal or catarrhal-purulent pneumonia. Hemorrhagic necrotizing pneumonia is a manifestation of actinobacillary pleuropneumonia. Interstitial (diffuse proliferative) pneumonia develops with viral pathogens - circovirus infection and reproductive and respiratory syndrome of pigs (PRRS). Serous fibrinous and fibrinous pleurisy develop in hemophilic polyserositis and actinobacillary pleuropneumonia. Pathomorphological changes of the lungs in the reproductive and respiratory syndrome of pigs are polymorphic and are manifested by the gradual progressive development of the inflammatory process from congestive hyperemia, acute catarrh to diffuse interstitial pneumonia. Pathomorphological changes of the lungs in mycoplasmosis (enzootic pleuropneumonia) of pigs are polymorphic and are manifested by the gradual progressive development of the inflammatory process, which is localized in the cranial, middle and peripheral parts of the diaphragmatic particles and is characterized by acute catarrhal bronchopneumonia. In actinobacillary pleuropneumonia pathohistological studies revealed a pronounced stage of morphological changes in the lungs and regional lymph nodes in actinobacillary pleuropneumonia. Depending on the form of the disease, serous-hemorrhagic exudation is exacerbated by fibrinogen exudation and increased migration of lymphocytes and mononuclear cells. In subacute and chronic forms of the disease, necrotic phenomena prevail in combination with areas of serous-fibrinous inflammation. In the future, further studies of immunohistochemical analysis to establish the tropism of the pathogen and the study of markers of lymphoid cells.


2018 ◽  
Vol 71 (15) ◽  
pp. 1696-1706 ◽  
Author(s):  
Arantxa González ◽  
Erik B. Schelbert ◽  
Javier Díez ◽  
Javed Butler

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