Therapeutic role of a synthesized calcium phosphate nanocomposite material on hepatocarcinogenesis in rats

2016 ◽  
Vol 94 (3) ◽  
pp. 279-288 ◽  
Author(s):  
Magdy Mohammed ◽  
Eman Abdel-Gawad ◽  
Sameh Awwad ◽  
Eman Kandil ◽  
Basma El-Agamy
Keyword(s):  
Body Mass ◽  
Caspase 3 ◽  
Histopathological Examination ◽  
Nanocomposite Material ◽  
Histopathological Analysis ◽  
Therapeutic Effects ◽  
Hsp 70 ◽  
Tnf Α ◽  
Ifn Γ ◽  
Metalloproteinase 9

Nanotechnology research is booming worldwide, and the general belief is that medical and biological applications will form the greatest sector of expansion over the next decade. With this in mind, this study was designed to evaluate the therapeutic effects of a synthesized tricalcium phosphate nanocomposite material (nano-TCP) on hepatocarcinoma in a rat model, as initiated with diethylnitrosamine (DEN) and promoted with phenobarbital (PB). Hepatocarcinoma was induced with intraperitoneal injections of DEN (50 mg·(kg body mass)−1) 3 times a week for 2 weeks. Three weeks after the last dose of DEN, the rats received PB (0.05 %, w/v) in their drinking water for a further 6 weeks. Nano-TCP (100 mg·(kg body mass)−1) was administered intraperitoneally 3 times per week to rats with HCC. At the end of the experimental period, liver samples were collected from all animals for biochemical and histopathological analysis. The degree of DNA fragmentation was analyzed, in addition to immune status, by measuring the levels of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin-2 (IL-2). The activities of the most important free-radical scavengers of the antioxidant defense system as well as malondialdehyde (MDA) content and liver enzymes were measured. The levels of hepatic heat shock protein-70 (HSP-70), caspase-3, and metalloproteinase-9 were also measured as markers for inflammation and apoptosis. Histopathological examination of liver tissue was performed. The results revealed the potent efficacy of nano-TCP in repairing the fragmented DNA and ameliorating most of the investigated parameters by significant elevation in the levels of hepatic alanine aminotransferase (ALT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities. On the other hand, there was a significant decrease in hepatic gamma-glutamyl transpeptidase (γ-GT), MDA, IL-2, IFN-γ, TNF-α, matrix metalloproteinase-9 (MMP-9), HSP-70, and caspase-3 levels upon treatment. The findings form histopathological examination of the liver tissues agreed with the biochemical results and confirmed the difference between the control and treatment groups. In conclusion, nano-TCP succeeded in treating hepatocarcinoma efficiently, and presents a new hope for patients to get safe, fast, and effective treatment.

scholarly journals A Complementary Herbal Product for Controlling Giardiasis

Antibiotics ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 477
Author(s):  
Tarek Hamdy Abd-Elhamid ◽  
Iman A. M. Abdel-Rahman ◽  
Amany Refaat Mahmoud ◽  
Khaled S. Allemailem ◽  
Ahmad Almatroudi ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Intestinal Inflammation ◽  
Artemisia Annua ◽  
Apoptotic Cell ◽  
Intraepithelial Lymphocytes ◽  
No Production ◽  
Therapeutic Effects ◽  
Tnf Α ◽  
Ifn Γ ◽  
Therapeutic Utility

Giardiasis is an intestinal protozoal disease caused by Giardia lamblia. The disease became a global health issue due to development of resistance to commonly used drugs. Since many plant-derived products have been used to treat many parasitic infestations, we aimed to assess the therapeutic utility of Artemisia annua (A. annua) for giardiasis. We showed that NO production was significantly reduced whereas serum levels of IL-6, IFN-γ, and TNF-α were elevated in infected hamsters compared to uninfected ones. Additionally, infection resulted in increased numbers of intraepithelial lymphocytes and reduced villi heights, goblet cell numbers, and muscularis externa thickness. We also showed that inducible NO synthase (iNOS) and caspase-3 were elevated in the intestine of infected animals. However, treatment with A. annua significantly reduced the intestinal trophozoite counts and IEL numbers, serum IL-6, IFN-γ, and TNF-α, while increasing NO and restoring villi heights, GC numbers, and ME thickness. Moreover, A. annua treatment resulted in lower levels of caspase-3, which indicates a protective effect from apoptotic cell death. Interestingly, A. annua therapeutic effects are comparable to metronidazole. In conclusion, our results show that A. annua extract is effective in alleviating infection-induced intestinal inflammation and pathological effects, which implies its potential therapeutic utility in controlling giardiasis.

scholarly journals Impressic Acid Ameliorates Atopic Dermatitis-Like Skin Lesions by Inhibiting ERK1/2-Mediated Phosphorylation of NF-κB and STAT1

2021 ◽  
Vol 22 (5) ◽  
pp. 2334
Author(s):  
Jae Ho Choi ◽  
Gi Ho Lee ◽  
Sun Woo Jin ◽  
Ji Yeon Kim ◽  
Yong Pil Hwang ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Skin Lesions ◽  
Histopathological Analysis ◽  
Mrna Levels ◽  
Chemokine Production ◽  
Dermal Thickness ◽  
Skin Symptoms ◽  
Tnf Α ◽  
Ifn Γ ◽  
In Cells

Impressic acid (IPA), a lupane-type triterpenoid from Acanthopanax koreanum, has many pharmacological activities, including the attenuation of vascular endothelium dysfunction, cartilage destruction, and inflammatory diseases, but its influence on atopic dermatitis (AD)-like skin lesions is unknown. Therefore, we investigated the suppressive effect of IPA on 2,4-dinitrochlorobenzene (DNCB)-induced AD-like skin symptoms in mice and the underlying mechanisms in cells. IPA attenuated the DNCB-induced increase in the serum concentrations of IgE and thymic stromal lymphopoietin (TSLP), and in the mRNA levels of thymus and activation regulated chemokine(TARC), macrophage derived chemokine (MDC), interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-13 (IL-13), tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) in mice. Histopathological analysis showed that IPA reduced the epidermal/dermal thickness and inflammatory and mast cell infiltration of ear tissue. In addition, IPA attenuated the phosphorylation of NF-κB and IκBα, and the degradation of IκBα in ear lesions. Furthermore, IPA treatment suppressed TNF-α/IFN-γ-induced TARC expression by inhibiting the NF-κB activation in cells. Phosphorylation of extracellular signalregulated protein kinase (ERK1/2) and the signal transducer and activator of transcription 1 (STAT1), the upstream signaling proteins, was reduced by IPA treatment in HaCaT cells. In conclusion, IPA ameliorated AD-like skin symptoms by regulating cytokine and chemokine production and so has therapeutic potential for AD-like skin lesions.

scholarly journals Protective effect of Toxocara vitulorum extract against alpha-naphthylisothiocyanate-induced cholangitis in rat

2020 ◽  
Vol 81 (1) ◽  
Author(s):  
Abeer Mahmoud Badr ◽  
Mohamed Farid ◽  
Ahmed Abdel Aziz Biomy ◽  
Ayman Saber Mohamed ◽  
Noha Ahmed Mahana ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Wistar Rat ◽  
Liver Function Tests ◽  
T Helper ◽  
Standard Drug ◽  
Toxocara Vitulorum ◽  
Stress Markers ◽  
Tnf Α ◽  
Ifn Γ ◽  
Antioxidant Markers

Abstract Background Cholestasis is the major cause of bile acid accumulation leading to liver damage. Chronic infection of worms can modulate the immune response towards T helper (Th)2-related cytokines. The present study aims to evaluate the protective impact of an ascarid nematode Toxocara vitulorum extract (TvE) against alpha-naphthylisothiocyanate (ANIT)-induced cholangitis male wistar rat model compared to ursodeoxycholic acid (UDCA) as a standard drug. Results Pretreatment with TvE and/or UDCA induced a marked reduction in the levels of liver function tests and malondialdehyde, while antioxidant markers were increased compared to cholestatic rats. Pretreatment with either TvE or combination before cholangitis induction attenuated the predominant Th1-related cytokines (IFN-γ and TNF-α) to Th2 (IL-13 and IL-10). TvE administration promoted higher expression levels of Bcl-2 protein and lower levels of caspase-3 compared to cholestatic rats. Conclusions Treatment with TvE has improved the liver functions and elevated the levels of oxidative stress markers. The upregulation of Th2-related cytokines and suppression of apoptosis through caspase-3 might be considered as a potential mechanism of TvE. Thereby, this natural extract revealed an opportunity for use in treatment of cholangitis disease.

scholarly journals Gomisin M2 Ameliorates Atopic Dermatitis-like Skin Lesions via Inhibition of STAT1 and NF-κB Activation in 2,4-Dinitrochlorobenzene/Dermatophagoides farinae Extract-Induced BALB/c Mice

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4409
Author(s):  
Jinjoo Kang ◽  
Soyoung Lee ◽  
Namkyung Kim ◽  
Hima Dhakal ◽  
Taeg-Kyu Kwon ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Oral Administration ◽  
Skin Diseases ◽  
Nuclear Translocation ◽  
Skin Lesions ◽  
Biologically Active ◽  
Therapeutic Effects ◽  
Dermatophagoides Farinae ◽  
Tnf Α ◽  
Ifn Γ

The extracts of Schisandra chinensis (Turcz.) Baill. (Schisandraceae) have various therapeutic effects, including inflammation and allergy. In this study, gomisin M2 (GM2) was isolated from S. chinensis and its beneficial effects were assessed against atopic dermatitis (AD). We evaluated the therapeutic effects of GM2 on 2,4-dinitrochlorobenzene (DNCB) and Dermatophagoides farinae extract (DFE)-induced AD-like skin lesions with BALB/c mice ears and within the tumor necrosis factor (TNF)-α and interferon (IFN)-γ-stimulated keratinocytes. The oral administration of GM2 resulted in reduced epidermal and dermal thickness, infiltration of tissue eosinophils, mast cells, and helper T cells in AD-like lesions. GM2 suppressed the expression of IL-1β, IL-4, IL-5, IL-6, IL-12a, and TSLP in ear tissue and the expression of IFN-γ, IL-4, and IL-17A in auricular lymph nodes. GM2 also inhibited STAT1 and NF-κB phosphorylation in DNCB/DFE-induced AD-like lesions. The oral administration of GM2 reduced levels of IgE (DFE-specific and total) and IgG2a in the mice sera, as well as protein levels of IL-4, IL-6, and TSLP in ear tissues. In TNF-α/IFN-γ-stimulated keratinocytes, GM2 significantly inhibited IL-1β, IL-6, CXCL8, and CCL22 through the suppression of STAT1 phosphorylation and the nuclear translocation of NF-κB. Taken together, these results indicate that GM2 is a biologically active compound that exhibits inhibitory effects on skin inflammation and suggests that GM2 might serve as a remedy in inflammatory skin diseases, specifically on AD.

scholarly journals Tailored Hydrogels as Delivery Platforms for Conditioned Medium from Mesenchymal Stem Cells in a Model of Acute Colitis in Mice

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1127
Author(s):  
Juan Sendon-Lago ◽  
Lorena Garcia-del Rio ◽  
Noemi Eiro ◽  
Patricia Diaz-Rodriguez ◽  
Leandro Avila ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Body Weight ◽  
Conditioned Medium ◽  
Local Treatment ◽  
Histopathological Analysis ◽  
Mrna Levels ◽  
Acute Colitis ◽  
Tnf Α ◽  
Ifn Γ

Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is increasingly prevalent and current therapies are not completely effective. Mesenchymal stem cells are emerging as a promising therapeutic option. Here, the effect of local hydrogel application loaded with conditioned medium (CM) from human uterine cervical stem cells (hUCESC-CM) in an experimental acute colitis mice model has been evaluated. Colitis induction was carried out in C57BL/6 mice by dissolving dextran sulfate sodium (DSS) in drinking water for nine days. Ulcers were treated by rectal administration of either mesalazine (as positive control) or a mucoadhesive and thermosensitive hydrogel loaded with hUCESC-CM (H-hUCESC-CM). Body weight changes, colon length, and histopathological analysis were evaluated. In addition, pro-inflammatory TNF-α, IL-6, and IFN-γ mRNA levels were measured by qPCR. Treatment with H-hUCESC-CM inhibited body weight loss and colon shortening and induced a significant decrease in colon mucosa degeneration, as well as TNF-α, IFN-γ, and IL-6 mRNA levels. Results indicate that H-hUCESC-CM effectively alleviated DSS-induced colitis in mice, suggesting that H-hUCESC-CM may represent an attractive cell-free therapy for local treatment of IBD.

Therapeutic effect of anti-OX40L and anti-TNF-α MAbs in a murine model of chronic colitis

2003 ◽  
Vol 284 (4) ◽  
pp. G595-G603 ◽  
Author(s):  
T. Totsuka ◽  
T. Kanai ◽  
K. Uraushihara ◽  
R. Iiyama ◽  
M. Yamazaki ◽  
...  
Keyword(s):  
T Cells ◽  
Crohn’S Disease ◽  
T Cell ◽  
Crohn's Disease ◽  
Lamina Propria ◽  
Therapeutic Effect ◽  
Therapeutic Effects ◽  
Chronic Colitis ◽  
Tnf Α ◽  
Ifn Γ

Interaction of OX40 (CD134) on T cells with its ligand (OX40L) on antigen-presenting cells has been implicated in pathogenic T cell activation. This study was performed to explore the involvement of OX40/OX40L in the development of T cell-mediated chronic colitis. We evaluated both the preventive and therapeutic effects of neutralizing anti-OX40L MAb on the development of chronic colitis in SCID mice induced by adoptive transfer of CD4+CD45RBhighT cells as an animal model of Crohn's disease. We also assessed the combination of anti-OX40L and anti-TNF-α MAbs to improve the therapeutic effect. Administration of anti-OX40L MAb markedly ameliorated the clinical and histopathological disease in preventive and therapeutic protocols. In vivo treatment with anti-OX40L MAb decreased CD4+T cell infiltration in the colon and suppressed IFN-γ, IL-2, and TNF-α production by lamina propria CD4+T cells. The combination with anti-TNF-α MAb further improved the therapeutic effect by abolishing IFN-γ, IL-2, and TNF-α production by lamina propria CD4+T cells. Our present results suggested a pivotal role of OX40/OX40L in the pathogenesis of T cell-mediated chronic colitis. The OX40L blockade, especially in combination with the TNF-α blockade, may be a promising strategy for therapeutic intervention of Crohn's disease.

Tumor necrosis factor-α in mechanic trauma plasma mediates cardiomyocyte apoptosis

2007 ◽  
Vol 293 (3) ◽  
pp. H1847-H1852 ◽  
Author(s):  
Shuzhuang Li ◽  
Xiangying Jiao ◽  
Ling Tao ◽  
Huirong Liu ◽  
Yue Cao ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Traumatic Injury ◽  
Cardiac Injury ◽  
Cardiomyocyte Apoptosis ◽  
Therapeutic Interventions ◽  
Tnf Α ◽  
Ifn Γ ◽  
Factor Α

Mechanical traumatic injury causes cardiomyocyte apoptosis and cardiac dysfunction. However, the signaling mechanisms leading to posttraumatic cardiomyocyte apoptosis remains unclear. The present study attempted to identify the molecular mechanisms responsible for cardiomyocyte apoptosis induced by trauma. Normal cardiomyocytes (NC) or traumatic cardiomyocytes (TC; isolated immediately after trauma) were cultured with normal plasma (NP) or traumatic plasma (TP; isolated 1.5 h after trauma) for 12 h, and apoptosis was determined by caspase-3 activation. Exposure of TC to NP failed to induce significant cardiomyocyte apoptosis. In contrast, exposure of NC to TP resulted in a greater than twofold increase in caspase-3 activation ( P < 0.01). Incubation of cardiomyocytes with cytomix (a mixture of TNF-α, IL-1β, and IFN-γ) or TNF-α alone, but not with IL-1β or IFN-γ alone, caused significant caspase-3 activation ( P < 0.01). TP-induced caspase-3 activation was virtually abolished by an anti-TNF-α antibody, and TP isolated from TNF-α−/− mice failed to induce caspase-3 activation. Moreover, incubation of cardiomyocytes with TP upregulated inducible nitric oxide (NO) synthase (iNOS)/NADPH oxidase expression, increased NO/superoxide production, and increased cardiomyocyte protein nitration (measured by nitrotyrosine content). These oxidative/nitrative stresses and the resultant cardiomyocyte caspase-3 activation can be blocked by neutralization of TNF-α (anti-TNF-α antibody), inhibition of iNOS (1400W), or NADPH oxidase (apocynin) and scavenging of peroxynitrite (FP15) ( P < 0.01). Taken together, our study demonstrated that there exists a TNF-α-initiated, cardiomyocyte iNOS/NADPH oxidase-dependent, peroxynitrite-mediated signaling pathway that contributes to posttraumatic myocardial apoptosis. Therapeutic interventions that block this signaling cascade may attenuate posttraumatic cardiac injury and reduce the incidence of secondary organ dysfunction after trauma.

A role for IL-1 receptor antagonist or other cytokines in the acute therapeutic effects of IVIg?

Blood ◽  
2006 ◽  
Vol 109 (1) ◽  
pp. 155-158 ◽  
Author(s):  
Andrew R. Crow ◽  
Seng Song ◽  
John W. Semple ◽  
John Freedman ◽  
Alan H. Lazarus
Keyword(s):  
Receptor Antagonist ◽  
Mechanism Of Action ◽  
Interleukin 1 ◽  
Serum Levels ◽  
Mouse Serum ◽  
Therapeutic Effects ◽  
Thrombocytopenic Purpura ◽  
Primary Mechanism ◽  
Tnf Α ◽  
Ifn Γ

Abstract The exact mechanism of action of IVIg in the amelioration of immune thrombocytopenic purpura (ITP) is still unclear. Studies have suggested that IVIg may function through the regulation of cytokines, including interleukin-1 receptor antagonist (IL-1Ra), an inhibitor of phagocytosis. Using a mouse model relevant to ITP, we confirm an increase in mouse serum levels of IL-1Ra after exposure to IVIg, yet a recombinant IL-1Ra did not ameliorate thrombocytopenia. IVIg has also been shown to affect the expression of other regulatory cytokines. We have also recently established that IVIg specifically targets activating FcγRs on CD11c+ dendritic cells (DCs) as its primary mechanism of action in the amelioration of murine ITP. Herein, we show that IVIg functions therapeutically in mice lacking specific cytokines or their receptors that can potentially affect DC/macrophage function (IL-1 receptor, IL-4, IL-10, IL-12β, TNF-α, IFN-γ receptor, MIP-1α). This suggests that while IVIg may mediate the release of a variety of cytokines, the cytokines tested do not directly participate in the mechanism of IVIg action.

Mechanism of attenuation of muscle protein degradation induced by tumor necrosis factor-α and angiotensin II by β-hydroxy-β-methylbutyrate

2008 ◽  
Vol 295 (6) ◽  
pp. E1417-E1426 ◽  
Author(s):  
Helen L. Eley ◽  
Steven T. Russell ◽  
Michael J. Tisdale
Keyword(s):  
Protein Degradation ◽  
P38 Mapk ◽  
Total Protein ◽  
Caspase 3 ◽  
Muscle Protein ◽  
Ang Ii ◽  
Tnf Α ◽  
Ros Formation ◽  
Ifn Γ ◽  
Factor Α

Both tumor necrosis factor-α (TNF-α)/interferon-γ (IFN-γ) and angiotensin II (ANG II) induced an increase in total protein degradation in murine myotubes, which was completely attenuated by treatment with β-hydroxy-β-methylbutyrate (HMB; 50 μM). There was an increase in formation of reactive oxygen species (ROS) within 30 min, as well as an increase in the activity of both caspase-3 and -8, and both effects were attenuated by HMB. Moreover, inhibitors of caspase-3 and -8 completely attenuated both ROS formation and total protein degradation induced by TNF-α/IFN-γ and ANG II. There was an increased autophosphorylation of double-stranded RNA-dependent protein kinase (PKR), which was attenuated by the specific caspase-3 and -8 inhibitors. Neither ROS formation or protein degradation occurred in myotubes expressing a catalytically inactive PKR variant, PKRΔ6, in response to TNF-α/IFN-γ, compared with myotubes expressing wild-type PKR, although there was still activation of caspase-3 and -8. HMB also attenuated activation of PKR, suggesting that it was important in protein degradation. Formation of ROS was attenuated by rotenone, an inhibitor of the mitochondrial electron transport chain, nitro-l-arginine methyl ester, an inhibitor of nitric oxide synthase, and SB 203580, a specific inhibitor of p38 mitogen-activated protein kinase (p38 MAPK), which also attenuated total protein degradation. Activation of p38 MAPK by PKR provides the link to ROS formation. These results suggest that TNF-α/IFN-γ and ANG II induce muscle protein degradation by a common signaling pathway, which is attenuated by HMB, and that this involves the initial activation of caspase-3 and -8, followed by autophosphorylation and activation of PKR, which then leads to increased ROS formation via activation of p38 MAPK. Increased ROS formation is known to induce protein degradation through the ubiquitin-proteasome pathway.

scholarly journals Expression of Toxoplasma gondii-Specific Heat Shock Protein 70 during In Vivo Conversion of Bradyzoites to Tachyzoites

1998 ◽  
Vol 66 (8) ◽  
pp. 3959-3963 ◽  
Author(s):  
Neide M. Silva ◽  
Ricardo T. Gazzinelli ◽  
Deise A. O. Silva ◽  
Eloisa A. V. Ferro ◽  
Lloyd H. Kasper ◽  
...  
Keyword(s):  
Heat Shock ◽  
Toxoplasma Gondii ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70 ◽  
Hsp 70 ◽  
Stage Conversion ◽  
Tnf Α ◽  
Specific Antigens ◽  
Ifn Γ

ABSTRACT Stage conversion between bradyzoites and tachyzoites was investigated in C57BL/6 mice chronically infected with the ME-49 strain of Toxoplasma gondii. In order to promote bradyzoite-tachyzoite conversion, mice were treated in vivo with neutralizing doses of anti-gamma interferon (IFN-γ) or anti-tumor necrosis factor alpha (TNF-α) antibodies. Expression of parasite-specific antigens SAG-1, SAG-2, and heat shock protein 70 (Hsp-70) was visualized in the central nervous system by immunocytochemistry and measured by photometric assay. The immunosuppressive effect of anti-IFN-γ or anti-TNF-α treatment was immediate, leading to parasite stage conversion as indicated by the increased expression of tachyzoite-specific antigens (SAG-1 and SAG-2) and by rapid parasite replication. We also observed expression of high levels of Hsp-70 during a short period of conversion of bradyzoites to tachyzoites. Our data suggest that Hsp-70 may have an important role in the process of bradyzoite-tachyzoite conversion during the reactivation of chronic toxoplasmosis.

Sign in / Sign up

Export Citation Format

Share Document