scholarly journals Shenmai Injection Alleviates Cardiomyocyte Apoptosis Induced by Doxorubicin

2021 ◽  
Author(s):  
Xiaonan Zhang ◽  
Yanyang Li ◽  
Wanqin Zhang ◽  
Qiujin Jia ◽  
Yaping Zhu ◽  
...  
Keyword(s):  
Protective Effect ◽  
Myocardial Injury ◽  
Myocardial Damage ◽  
Myocardial Cell ◽  
Type Iii Collagen ◽  
Type I ◽  
Pathological Changes ◽  
Sprague Dawley ◽  
Shenmai Injection

Abstract Background: Shenmai Injection (SMI) is a patented Chinese medicine extract, has been widely used to treat myocardial damage caused by doxorubicin (DOX), but its underlying mechanisms remain elusive. The study aimed to explore the protective effect of SMI on myocardial injury caused by DOX in vivo.Methods: The male Sprague-Dawley (SD) rats received DOX (2mg/kg) tail vein injection every week for 4 weeks, with or without SMI and miR-30a agomir treatment for 2 weeks. The protective effect of SMI on myocardial injury caused by DOX has been determined by measuring rat body mass and general heart morphology, myocardial pathological changes, and serum markers. The myocardial pathological changes were observed by Van Gieson (VG) staining, the serum marker levels of myocardial injury were detected by ELISA, the myocardial cell apoptosis was observed by TUNEL assay and transmission electron microscope, and the expression of target protein was detected by Western Blot.Results: SMI treatment significantly reduced rat HMI and LVMI, reduced the levels of serum CK, LDH, cTnT, NT-proBNP, and also reduced the levels of serum sST2 and GDF-15, and reduced the expression of rat myocardial type I and type III collagen, which was effective reduce the fibrosis of myocardial collagen knot tissue and interstitial. The study further found that SMI can increase the expression of Bcl-2 protein, reduce the expression of Bax, Caspase-9, and Caspase-3 protein, and reduce the apoptotic index of cardiomyocytes. Conclusion: The potential mechanism of SMI on cardiomyocytes from apoptosis induced by the DOX may be attributed to the regulation of miR-30a/beclin 1.

Type VI collagen induces cardiac myofibroblast differentiation: implications for postinfarction remodeling

2006 ◽  
Vol 290 (1) ◽  
pp. H323-H330 ◽  
Author(s):  
Jennifer E. Naugle ◽  
Erik R. Olson ◽  
Xiaojin Zhang ◽  
Sharon E. Mase ◽  
Charles F. Pilati ◽  
...  
Keyword(s):  
Cardiac Fibrosis ◽  
Type I Collagen ◽  
In Vivo Model ◽  
Type Iii Collagen ◽  
Type I ◽  
Myofibroblast Differentiation ◽  
Type Vi Collagen ◽  
Collagen Substrate ◽  
Type Iii

Cardiac fibroblast (CF) proliferation and differentiation into hypersecretory myofibroblasts can lead to excessive extracellular matrix (ECM) production and cardiac fibrosis. In turn, the ECM produced can potentially activate CFs via distinct feedback mechanisms. To assess how specific ECM components influence CF activation, isolated CFs were plated on specific collagen substrates (type I, III, and VI collagens) before functional assays were carried out. The type VI collagen substrate potently induced myofibroblast differentiation but had little effect on CF proliferation. Conversely, the type I and III collagen substrates did not affect differentiation but caused significant induction of proliferation (type I, 240.7 ± 10.3%, and type III, 271.7 ± 21.8% of basal). Type I collagen activated ERK1/2, whereas type III collagen did not. Treatment of CFs with angiotensin II, a potent mitogen of CFs, enhanced the growth observed on types I and III collagen but not on the type VI collagen substrate. Using an in vivo model of myocardial infarction (MI), we measured changes in type VI collagen expression and myofibroblast differentiation after post-MI remodeling. Concurrent elevations in type VI collagen and myofibroblast content were evident in the infarcted myocardium 20-wk post-MI. Overall, types I and III collagen stimulate CF proliferation, whereas type VI collagen plays a potentially novel role in cardiac remodeling through facilitation of myofibroblast differentiation.

scholarly journals Evaluation of Soft Tissue Regenerative Processes After Subcutaneous Implantation of Silver/ Poly(Vinyl Alcohol) and Novel Silver/Poly(Vinyl Alcohol)/Graphene Hydrogels in an Animal Model

2021 ◽  
Vol 71 (3) ◽  
pp. 285-302
Author(s):  
Tijana Lužajić Božinovski ◽  
Vera Todorović ◽  
Ivan Milošević ◽  
Vladimir Gajdov ◽  
Bogomir Bolka Prokić ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Vinyl Alcohol ◽  
International Standards ◽  
Wound Dressings ◽  
Poly Vinyl Alcohol ◽  
Type Iii Collagen ◽  
Type I ◽  
Subcutaneous Implantation ◽  
Ki 67

Abstract A newly produced biomaterial is necessarily subject of standards, which are performed in vivo on animal models. For the evaluation of soft tissue regenerative possibilities after subcutaneous implantation of biomaterials – silver/poly(vinyl alcohol) (Ag/PVA) and novel silver/poly(vinyl alcohol)/graphene (Ag/PVA/Gr) provided for clinical use, sixteen rats were used, according to the instructions of international standards, ISO 10993-6, 2007. Histological sections were observed 7, 15, 30 and 60 days after grafting. These hydrogels were produced by in situ electrochemical synthesis of silver nanoparticles in the polymer matrices, which enabled obtaining completely safe and biocompatible materials, free from any additional toxic chemical reducing agents. Surgical implantation of hydrogels was done according to the permission of the Ethical Committee of the Faculty of Veterinary Medicine, University of Belgrade. Immunohistochemical (IHC) studies included the assessment of smooth muscle expression actin in blood vessels (α-SMA), the expression of laminin and type I and type III collagen in the skin structures, and, the determination of cell proliferation marker expression (Ki-67) keratinocytes. The results were assessed in a semiquantitative manner. The data were analyzed in the statistical software package IBM SPSS 20. The conclusions indicated that Ag/PVA/Gr might be used as wound dressings to enhance the tissue healing potential and established faster integration and shorter retention in the tissue.

PHARMACOLOGICAL STUDIES OF PLATELET ANTIAGGREGANTS USING AN IN VITRO MODEL OF PRIMARY HEMOSTASIS.

1987 ◽  
Author(s):  
S Bellucci ◽  
E Cambau ◽  
B Candalot ◽  
J P Caen
Keyword(s):  
Ex Vivo ◽  
Repeated Measurements ◽  
New Drugs ◽  
Type Iii Collagen ◽  
Type I ◽  
Glass Capillary ◽  
New Device ◽  
Primary Hemostasis

We used a new device simulating in vitro primary haemostasis : more precisely the reactivity of blood to collagen and ADP. Thus an artificial vessel was created consisting of two main parts : a glass capillary (ID 140 um, length 16 mm, siliconized) simulating the haemodynamic resistance of an arteriole and an aperture (ID 150 um) reflecting the injured part of a cut arteriole. This aperture was performed in a cellulose acetate filter covered with collagen type I (3 mg/ml) to provide a defined surface for the adhesion of platelets and soaked with ADP in a concentration similar to that of injured endothelial cells (2 x 10-2 M). The mean - sd control values were 110 ± 24 s, 156 -± 40 ul (n = 25) and correlated well with in vivo bleeding time values (p< 0.01). We studied the effect on this test of classical antiaggregant drugs which act on primary hemostasis by different mechanisms of action. Acetylsalycilic acid (Egic laboratories) prolonged this test for concentrations above 10−5 M, ticlopidine (Millot-Solac laboratories) above 3 × 10−4 M, prostacyclin (Wellcome laboratories) above 5 Õ 10−9 M, the synthetic octapeptide LYS-PRO-GLY-GLU-PRO-GLY-PR0-LYS derived from type III collagen (gift from Y. Legrand) above 5 × 10−4 M. We evidenced a synergistic action between collagen octapeptide and ticlopidine. Thus this device permits the screening of new drugs for their effects on primary hemostasis and the study of ex vivo repeated measurements for the monitoring of antiaggregant therapy.

scholarly journals Protective effect of Shenmai injection on doxorubicin-induced cardiotoxicity via regulation of inflammatory mediators

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Sheng Zhang ◽  
Zhen-Qiang You ◽  
Lin Yang ◽  
Li-Li Li ◽  
You-Ping Wu ◽  
...  
Keyword(s):  
Protective Effect ◽  
Inflammatory Mediators ◽  
Inflammatory Cytokine ◽  
Malignant Tumors ◽  
Cardiac Injury ◽  
Viral Myocarditis ◽  
Heart Tissue ◽  
Shenmai Injection ◽  
Cytokine Detection

Abstract Background Doxorubicin (DOX) is a chemotherapy drug for malignant tumors. The clinical application of DOX is limited due to its dosage relative cardiotoxicity. Oxidative damage and cardiac inflammation appear to be involved in DOX-related cardiotoxicity. Shenmai injection (SMI), which mainly consists of Panax ginsengC.A.Mey.and Ophiopogon japonicus (Thunb.) Ker Gawl, is widely used for the treatment of atherosclerotic coronary heart disease and viral myocarditis in China. In this study, we investigated the protective effect of Shenmai injection on doxorubicin-induced acute cardiac injury via the regulation of inflammatory mediators. Methods Male ICR mice were randomly divided into seven groups: control, DOX (10 mg/kg), SMI (5 g/kg), DOX with pretreatment with SMI (0.5 g/kg, 1.5 g/kg or 5 g/kg) and DOX with post-treatment with SMI (5 g/kg). Forty-eight hours after the last DOX administration, all mice were anesthetized for ultrasound echocardiography. Then, serum was collected for biochemical and inflammatory cytokine detection, and heart tissue was collected for histological and Western blot detection. Results A cumulative dose of DOX (10 mg/kg) induced acute cardiotoxicity in mice manifested by altered echocardiographic outcome, and increased tumor necrosis factor, interleukin 6 (IL-6), monocyte chemotactic protein 1, interferon-γ, and serum AST and LDH levels, as well as cardiac cytoplasmic vacuolation and myofibrillar disarrangement. DOX also caused the increase in the expression of IKK-α and iNOS and produced a large amount of NO, resulting in the accumulation of nitrotyrosine in the heart tissue. Pretreatment with SMI elicited a dose-dependent cardioprotective effect in DOX-dosed mice as evidenced by the normalization of serum inflammatory mediators, as well as improve dcardiac function and myofibril disarrangement. Conclusions SMI could recover inflammatory cytokine levels and suppress the expression of IKK-α and iNOS in vivo, which was increased by DOX. Overall, there was evidence that SMI could ameliorate DOX-induced cardiotoxicity by inhibiting inflammation and recovering heart dysfunction.

scholarly journals Basic fibroblast growth factor modulates proliferation and collagen expression in urinary bladder smooth muscle cells

2007 ◽  
Vol 293 (4) ◽  
pp. F1007-F1017 ◽  
Author(s):  
Masaaki Imamura ◽  
Akihiro Kanematsu ◽  
Shingo Yamamoto ◽  
Yu Kimura ◽  
Isao Kanatani ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Type I Collagen ◽  
Type Iii Collagen ◽  
Type I ◽  
Fibroblast Growth ◽  
Bladder Smooth Muscle ◽  
Type Iii ◽  
Collagen Expression

Bladder hypertrophy is a general consequence of bladder outlet obstruction (BOO) and a typical phenomenon observed in clinical urologic diseases such as benign prostatic hyperplasia and neurogenic bladder. It is characterized by smooth muscle hyperplasia, altered extracellular matrix composition, and increased contractile function. Various growth factors are likely involved in hypertrophic pathophysiology, but their functions remain unknown. In this report, the role of basic fibroblast growth factor (bFGF) was investigated using a rat bladder smooth muscle cell (BSMC) culture system and an original animal model, in which bFGF was released from a gelatin hydrogel directly onto rat bladders. bFGF treatment promoted BSMC proliferation both in vitro and in vivo. In vitro, bFGF downregulated the expression of type I collagen, but upregulated type III collagen. ERK1/2, but not p38MAPK, was activated by bFGF, whereas inhibition of ERK1/2 by PD98059 reversed bFGF-induced BSMC proliferation, type I collagen downregulation, and type III collagen upregulation. In the in vivo release model, bFGF upregulated type III collagen and increased the contractile force of treated bladders. In parallel with these findings, hypertrophied rat bladders created by urethral constriction showed increased urothelial bFGF expression, BSMC proliferation, and increased type III collagen expression compared with sham-operated rats. These data suggest that bFGF from the urothelium could act as a paracrine signal that stimulates the proliferation and matrix production of BSMC, thereby contributing to the hypertrophic remodeling of the smooth muscle layer.

scholarly journals A Novel Microspheres Formulation of Puerarin: Pharmacokinetics Study and In Vivo Pharmacodynamics Evaluations

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Xiao Song ◽  
Xihui Bai ◽  
Shiyu Liu ◽  
Linjuan Dong ◽  
Hui Deng ◽  
...  
Keyword(s):  
Protective Effect ◽  
Myocardial Injury ◽  
B Cell Lymphoma ◽  
Serum Levels ◽  
Intragastric Administration ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Promising Candidate ◽  
Oral Preparation ◽  
Total Superoxide Dismutase

The aim of this study was to investigate the pharmacokinetics and pharmacodynamics of puerarin loaded carboxymethyl chitosan microspheres (Pue-CCMs). The differences in pharmacokinetics parameters of rats after intragastric administration of Pue-CCMs and puerarin were investigated using HPLC. To assess the protective effect of Pue-CCMs on myocardial injury in rats, serum levels of creatine kinase (CK), lactate dehydrogenase (LDH), total superoxide dismutase (T-SOD), and malondialdehyde (MDA) were measured, in addition to pathological examinations and immunohistochemical staining. Our present study has shown that the AUC0–t, Cmax, Tmax, MRT0–t of Pue-CCMs, and puerarin were 20.176 mg·h/L, 3.778 μg/mL, 1 h, 4.634 h and 9.474 mg·h/L, 2.618 μg/mL, 0.542 h, and 3.241 h, respectively. Pue-CCMs alleviated myocardial ischemic injury. Pretreatment with Pue-CCMs could significantly decrease CK, LDH, and MDA levels and increase T-SOD level in the serum. Pue-CCMs downregulated expression of the Bcl-2 associated X protein (Bax) and upregulated B-cell lymphoma-2 (Bcl-2) expression. Compared with puerarin group, the Pue-CCMs group could improve the oral bioavailability of puerarin. The protective effect of Pue-CCMs against myocardial injury was significantly greater than puerarin at the same dose. In summary, Pue-CCMs should be a qualified and promising candidate as a new oral preparation of puerarin.

scholarly journals RIP1/RIP3/MLKL-mediated necroptosis contributes to vinblastine-induced myocardial damage

2020 ◽  
Author(s):  
Huiling Zhou ◽  
Lijun Liu ◽  
Xiaolong Ma ◽  
Jian Wang ◽  
Jinfu Yang ◽  
...  
Keyword(s):  
Ventricular Myocytes ◽  
Cell Damage ◽  
Animal Experiments ◽  
Myocardial Damage ◽  
Myocardial Cell ◽  
Neonatal Rat ◽  
H9c2 Cells ◽  
Interacting Protein

AbstractVinblastine (VBL) has been considered as a first-line anti-tumor drug for many years. However, vinblastine-caused myocardial damage has been continually reported. The underlying molecular mechanism of the myocardial damage remains unknown. Here, we show that vinblastine induces myocardial damage and necroptosis is involved in the vinblastine-induced myocardial damage both in vitro and in vivo. The results of WST-8 and flow cytometry analysis show that vinblastine causes damage to H9c2 cells, and the results of animal experiments show that vinblastine causes myocardial cell damage. The necrosome components, receptor-interacting protein 1 (RIP1) receptor-interacting protein 3 (RIP3), are significantly increased in vinblastine-treated H9c2 cells, primary neonatal rat ventricular myocytes and rat heart tissues. And the downstream substrate of RIP3, mixed lineage kinase domain like protein (MLKL) was also increased. Pre-treatment with necroptosis inhibitors partially inhibits the necrosome components and MLKL levels and alleviates vinblastine-induced myocardial injury both in vitro and in vivo. This study indicates that necroptosis participated in vinblastine-evoked myocardial cell death partially, which would be a potential target for relieving the chemotherapy-related myocardial damage.

scholarly journals Analysis of collagen types synthesized by rabbit ear cartilage chondrocytes in vivo and in vitro

1984 ◽  
Vol 221 (1) ◽  
pp. 189-196 ◽  
Author(s):  
K Madsen ◽  
K von der Mark ◽  
M van Menxel ◽  
U Friberg
Keyword(s):  
Type I Collagen ◽  
Polyacrylamide Gel Electrophoresis ◽  
Type Ii Collagen ◽  
Type Iii Collagen ◽  
Type I ◽  
Type Ii ◽  
Collagen Types ◽  
Rabbit Ear ◽  
Ear Cartilage

This study compares the collagen types present in rabbit ear cartilage with those synthesized by dissociated chondrocytes in cell culture. The cartilage was first extracted with 4M-guanidinium chloride to remove proteoglycans. This step also extracted type I collagen. After pepsin solubilization of the residue, three additional, genetically distinct collagen types could be separated by fractional salt precipitation. On SDS (sodium dodecyl sulphate)/polyacrylamide-gel electrophoresis they were identified as type II collagen, (1 alpha, 2 alpha, 3 alpha) collagen and M-collagen fragments, a collagen pattern identical with that found in hyaline cartilage. Types I, II, (1 alpha, 2 alpha, 3 alpha) and M-collagen fragments represent 20, 75, 3.5, and 1% respectively of the total collagen. In frozen sections of ear cartilage, type II collagen was located by immunofluorescence staining in the extracellular matrix, whereas type I collagen was closely associated with the chondrocytes. Within 24h after release from elastic cartilage by enzymic digestion, auricular chondrocytes began to synthesize type III collagen, in addition to the above-mentioned collagens. This was shown after labelling of freshly dissociated chondrocytes with [3H]proline 1 day after plating, fractionation of the pepsin-treated collagens from medium and cell layer by NaCl precipitation, and analysis of the fractions by CM(carboxymethyl)-cellulose chromatography and SDS/polyacrylamide-gel electrophoresis. The 0.8 M-NaCl precipitate of cell-layer extracts consisted predominantly of type II collagen. The 0.8 M-NaCl precipitate obtained from the medium contained type I, II, and III collagen. In the supernatant of the 0.8 M-NaCl precipitation remained, both in the cell extract and medium, predominantly 1 alpha-, 2 alpha-, and 3 alpha-chains and M-collagen fragments. These results indicate that auricular chondrocytes are similar to chondrocytes from hyaline cartilage in that they produce, with the exception of type I collagen, the same collagen types in vivo, but change their cellular phenotype more rapidly after transfer to monolayer culture, as indicated by the prompt onset of type III collagen synthesis.

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