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Topic:Cytotoxicity

Cytotoxicity refers to the quality of being toxic to cells. In horses, cytotoxicity is considered in various contexts, including the evaluation of pharmaceuticals, the impact of toxins, and the immune response to infections or neoplastic processes. Assessing cytotoxicity involves measuring the extent to which substances or immune cells can cause damage or cell death. This topic is relevant to understanding the safety and efficacy of therapeutic agents, as well as the pathological mechanisms underlying certain diseases. This page compiles peer-reviewed research studies and scholarly articles that investigate the mechanisms, assessment methods, and implications of cytotoxicity in equine health.
The role of RTX toxins in host specificity of animal pathogenic Pasteurellaceae.
Veterinary microbiology    May 19, 2011   Volume 153, Issue 1-2 51-58 doi: 10.1016/j.vetmic.2011.05.018
Frey J.RTX toxins are bacterial pore-forming toxins that are particularly abundant among pathogenic species of Pasteurellaceae, in which they play a major role in virulence. RTX toxins of several primary pathogens of the family of Pasteurellaceae are directly involved in causing necrotic lesions in the target organs. Many RTX toxins are known as haemolysins because they lyse erythrocytes in vitro, an effect that is non-specific, but which serves as a useful marker in bacteriological identification and as an easily measurable signal in vitro in experimental studies. More recent studies have shown that...
Lipoprotein complex of equine lysozyme with oleic acid (ELOA) interactions with the plasma membrane of live cells.
Langmuir : the ACS journal of surfaces and colloids    August 26, 2010   Volume 26, Issue 18 14782-14787 doi: 10.1021/la1026416
Vukojević V, Bowen AM, Wilhelm K, Ming Y, Ce Z, Schleucher J, Hore PJ, Terenius L, Morozova-Roche LA.Recent evidence supports the idea that early aggregates, protein, and lipoprotein oligomers but not large aggregates like fibrils that are formed at late stages of the aggregation process are responsible for cytotoxicity. Oligomers can interact with the cellular plasma membrane affecting its structure and/or dynamics or may be taken up by the cells. In either case, disparate cascades of molecular interactions are activated in the attempt to counteract the disturbance induced by the oligomers. If unsuccessful, cell death follows. Here, we study the molecular and cellular mechanisms underlying P...
Protein oligomerization induced by oleic acid at the solid-liquid interface–equine lysozyme cytotoxic complexes.
The FEBS journal    July 7, 2009   Volume 276, Issue 15 3975-3989 doi: 10.1111/j.1742-4658.2009.07107.x
Wilhelm K, Darinskas A, Noppe W, Duchardt E, Mok KH, Vukojević V, Schleucher J, Morozova-Roche LA.Protein oligomeric complexes have emerged as a major target of current research because of their key role in aggregation processes in living systems and in vitro. Hydrophobic and charged surfaces may favour the self-assembly process by recruiting proteins and modifying their interactions. We found that equine lysozyme assembles into multimeric complexes with oleic acid (ELOA) at the solid-liquid interface within an ion-exchange chromatography column preconditioned with oleic acid. The properties of ELOA were characterized using NMR, spectroscopic methods and atomic force microscopy, and showed...
A mycolyl transferase mutant of Rhodococcus equi lacking capsule integrity is fully virulent.
Veterinary microbiology    October 25, 2007   Volume 128, Issue 3-4 327-341 doi: 10.1016/j.vetmic.2007.10.020
Sydor T, von Bargen K, Becken U, Spuerck S, Nicholson VM, Prescott JF, Haas A.Rhodococcus equi is a mucoid Gram-positive facultative intracellular pathogen which can cause severe bronchopneumonia in foals and AIDS patients. A polysaccharide capsule which gives R. equi a mucoid appearance has long been suspected to be a virulence factor. Here, we describe a transposome mutant in the gene fbpA of strain R. equi 103 causing absence of a capsular structure. FbpA is a chromosomal gene homologous to antigen 85 (Ag85) mycolyl chain transferase gene of Mycobacterium tuberculosis. The mutant multiplied normally in isolated macrophages, was able to establish the unusual R. equi-c...
In vitro effects of fungi isolated from equine hooves on primary human keratinocytes.
Medical mycology    November 28, 2006   Volume 44, Issue 8 715-722 doi: 10.1080/13693780600932950
Apprich V, Spergser J, Rosengarten R, Stanek C.The effects of two dermatophytes (Microsporum gypseum and Trichophyton mentagrophytes) and four moulds (Scopulariopsis brevicaulis, Alternaria alternata, Geotrichum candidum and Penicillium spp.) on living keratinocyte cultures were examined in vitro using primary human keratinocytes. Rates of apoptosis of infected cells were determined using a colorimetric TUNEL system which detects the characteristic nuclear DNA fragmentation of apoptotic cells. The cytotoxicity of the individual fungi was tested by quantitatively measuring cytosolic enzyme lactate dehydrogenase, released upon cell lysis, in...
Intermediate amyloid oligomers of lysozyme: Is their cytotoxicity a particular case or general rule for amyloid?
Biochemistry. Biokhimiia    May 31, 2006   Volume 71, Issue 5 505-512 doi: 10.1134/s0006297906050063
Malisauskas M, Darinskas A, Zamotin VV, Gharibyan A, Kostanyan IA, Morozova-Roche LA.In the current study we investigated the molecular mechanisms of cytotoxicity of amyloid oligomers of horse milk lysozyme. We have shown that lysozyme forms soluble amyloid oligomers and protofibrils during incubation at pH 2.0 and 4.5 and 57 degrees C. These structures bind the amyloid-specific dyes thioflavin T and Congo Red, and their morphology and size were analyzed by atomic force microscopy. Monomeric lysozyme and its fibrils did not affect the viability of three cell types used in our experiments including primary murine neurons and fibroblasts, as well as neuroblastoma cell line IMR-3...
Report of the equine herpesvirus-1 Havermeyer Workshop, San Gimignano, Tuscany, June 2004.
Veterinary immunology and immunopathology    March 20, 2006   Volume 111, Issue 1-2 3-13 doi: 10.1016/j.vetimm.2006.01.004
Slater JD, Lunn DP, Horohov DW, Antczak DF, Babiuk L, Breathnach C, Chang YW, Davis-Poynter N, Edington N, Ellis S, Foote C, Goehring L, Kohn CW....Amongst the infectious diseases that threaten equine health, herpesviral infections remain a world wide cause of serious morbidity and mortality. Equine herpesvirus-1 infection is the most important pathogen, causing an array of disorders including epidemic respiratory disease abortion, neonatal foal death, myeloencephalopathy and chorioretinopathy. Despite intense scientific investigation, extensive use of vaccination, and established codes of practice for control of disease outbreaks, infection and disease remain common. While equine herpesvirus-1 infection remains a daunting challenge for i...
Oxidative DNA damage induced by equine estrogen metabolites: role of estrogen receptor alpha.
Chemical research in toxicology    April 16, 2002   Volume 15, Issue 4 512-519 doi: 10.1021/tx0101649
Liu X, Yao J, Pisha E, Yang Y, Hua Y, van Breemen RB, Bolton JL.Excessive exposure to synthetic and endogenous estrogens has been associated with the development of cancer in several tissues. 4-Hydroxyequilenin (4-OHEN), a major metabolite of equine estrogens present in estrogen replacement formulations, has been shown to induce cytotoxic/carcinogenic effects. In the present study, we have found that 4-OHEN caused DNA damage in breast cancer cells, and cells that contain estrogen receptor alpha (S30) are more sensitive to 4-OHEN-mediated DNA damage as compared to estrogen receptor negative cells (MDA-MB-231). For example, concentration-dependent increases ...
Effects of enrofloxacin and ciprofloxacin hydrochloride on canine and equine chondrocytes in culture.
American journal of veterinary research    May 9, 2001   Volume 62, Issue 5 704-708 doi: 10.2460/ajvr.2001.62.704
Egerbacher M, Edinger J, Tschulenk W.To study chondrotoxic effects of enrofloxacin (ENR) and ciprofloxacin hydrochloride (CFX) on canine and equine articular chondrocytes in culture and to compare the effects with that of cultivation in Mg2+-free medium. Methods: Chondrocytes from articular cartilage of 4- and 6 -month old dogs and 2- to 4- year-old horses. Methods: Chondrocytes were cultivated with 10, 40, 80, and 160 microg of CFX/ml, 10, 50, 100, and 150 microg of ENR/ml, or in Mg2+-free medium. A live-to-dead test was performed to test cytotoxic effects. Morphologic changes were evaluated by electron microscopy. An attachment...
Cytotoxicity of stimulated equine neutrophils on equine endothelial cells in culture.
Equine veterinary journal    August 22, 2000   Volume 32, Issue 4 327-333 doi: 10.2746/042516400777032273
Benbarek H, Grülke S, Deby-Dupont G, Deby C, Mathy-Hartert M, Caudron I, Dessy-Doize C, Lamy M, Serteyn D.We studied the interactions of isolated equine neutrophils with endothelial cells in culture, mimicking a situation of acute inflammation. Our main purpose was to demonstrate that the supernatant of activated neutrophils was sufficient to damage endothelial cells. Equine endothelial cells (from carotid arteries) were covered either with increased numbers of equine neutrophils stimulated by phorbol myristate acetate, or with the supernatant collected after an in vitro stimulation of the neutrophils. Cytotoxicity was estimated by the release of preincorporated 51Cr, and by light microscopy obser...
Intralesional and topical chemotherapy and immunotherapy.
The Veterinary clinics of North America. Equine practice    January 19, 1999   Volume 14, Issue 3 659-viii doi: 10.1016/s0749-0739(17)30191-8
Théon AP.Surgery is the mainstay of treatment for equine tumors. Conservative treatment approaches which preserve function and appearance are increasingly used in clinical practice. This article covers the principles and applications of two conservative treatment modalities including local chemotherapy and immunotherapy. The therapeutic benefit of local chemotherapy is based on the direct drug delivery to tumor tissue, i.e., topical and intratumoral administration of cytotoxic agents in slow release formulation. This treatment modality is very effective for cutaneous tumors and does not result in any p...
Control of equine infectious anemia virus is not dependent on ADCC mediating antibodies.
Virology    April 14, 1997   Volume 230, Issue 2 275-280 doi: 10.1006/viro.1997.8502
Tschetter JR, Byrne KM, Perryman LE, McGuire TC.Horses infected with equine infectious anemia virus (EIAV) have recurrent episodes of viremia which are eventually controlled, but the immune mechanisms have not been identified. Antibodies were detected to the surface of EIAV-infected cells within 1 month postinfection and remained for at least 3.5 years postinfection. These antibodies recognized cell surface-exposed envelope (Env) glycoproteins, but could not mediate antibody dependent cellular cytotoxicity (ADCC) using EIAV-WSU5-infected equine kidney (EK) cells as targets and peripheral blood mononuclear cells (PBMC) or polymorphonuclear c...
Susceptibility of equine chorionic girdle cells to lymphokine-activated killer cell activity.
American journal of reproductive immunology (New York, N.Y. : 1989)    September 1, 1996   Volume 36, Issue 3 184-190 doi: 10.1111/j.1600-0897.1996.tb00160.x
Vagnoni KE, Schram BR, Ginther OJ, Lunn DP.Equine chorionic girdle cells are a subpopulation of highly invasive trophoblast cells that attach and invade the uterine epithelium on Day 35 (Day 0 = day of ovulation). These invading chorionic girdle cells form endometrial cups that are associated with a marked local maternal leukocytic response that may result in the demise of the cups at Day 120 of pregnancy. Once endometrial cups become established in the uterine wall they do not express MHC antigens, and therefore may only be susceptible to non-MHC restricted cytotoxic cells. The susceptibility of cultured chorionic girdle cells to LAK ...
Serum can inhibit reversal of multidrug resistance by chemosensitisers.
European journal of cancer (Oxford, England : 1990)    May 1, 1996   Volume 32A, Issue 5 862-867 doi: 10.1016/0959-8049(96)00004-4
Lehnert M, de Giuli R, Kunke K, Emerson S, Dalton WS, Salmon SE.The purpose of this study was to evaluate to what extent the ability of various chemosensitisers (CS) to reverse P-glycoprotein-associated multidrug resistance (MDR) is reduced when tested in physiological serum protein concentrations. Utilising drug sensitivity and accumulation assays, the CS were tested in medium containing 10% fetal bovine serum and in 100% horse or human serum. Two RPMI 8226 human myeloma sublines were used which express different levels of P-glycoprotein. The CS were tested at various concentrations, including clinically achievable blood levels. When using the CS at high ...
Isolation and characterization of four basic proteins from horse eosinophilic granules.
Biochemical and biophysical research communications    April 30, 1993   Volume 192, Issue 2 373-380 doi: 10.1006/bbrc.1993.1425
Piller K, Portmann P.Four new basic proteins were isolated from horse eosinophils and purified. The eosinophils release these proteins after permeabilization with saponin and degranulation stimulized by guanosine 5'-O-thiotriphosphate. The proteins were separated and purified on a Superose P12- and a Mono S-column by fast protein liquid chromatography. The amino acid composition, the relative molecular mass, the isoelectric point and the partial N-terminal sequence of the four proteins were determined. Papain-activation and ribonuclease activity of the four proteins were tested for comparison with the human eosino...
Exercise-induced phospholipid degradation in the equine skeletal muscle and erythrocytes.
The Journal of veterinary medical science    December 1, 1991   Volume 53, Issue 6 1001-1007 doi: 10.1292/jvms.53.1001
Matsuki N, Tamura S, Ono K, Watari T, Goitsuka R, Yamanobe A, Hiraga A, Kubo K, Takagi S, Hasegawa A.To understand the pathogenesis of equine exercise-induced myopathies and hemolysis, changes of phospholipid peroxidation products in the equine middle gluteal muscle and erythrocytes following the high-speed treadmill exercise were studied. In the skeletal muscle, the peroxidized phosphatidylethanolamine (PE) were increased at 24 hours after the exercise. The malondialdehydes (MDAs) were also increased as the protein-bound MDAs following exercise. In the erythrocytes, the peroxidized PE were significantly decreased at 24 hours after the exercise. The protein-bound MDAs were significantly incre...
Tumor necrosis factor activity in the circulation of horses given endotoxin.
American journal of veterinary research    April 1, 1991   Volume 52, Issue 4 533-538 
MacKay RJ, Merritt AM, Zertuche JM, Whittington M, Skelley LA.Serum and plasma from horses injected with endotoxin was examined for cytotoxic activity. Each of the cell lines, L929 and WEHI 164 clone 13, was sensitive to the cytotoxic effects of equine serum; however, a precipitation artifact caused by the use of isopropanol in the WEHI assay limited the use of this assay to samples containing less than 2 mg of protein/ml. In foals treated with a sublethal IV bolus of 5 micrograms of lipopolysaccharide (LPS)/kg and in adult horses given a low-dose continuous infusion of LPS (30 ng/kg/h for 4 hours), cytotoxic activity was detected in all serum or plasma ...
Comparative toxicity of the horse eosinophil peroxidase-H2O2-halide system and granule basic proteins.
Journal of immunology (Baltimore, Md. : 1950)    July 1, 1989   Volume 143, Issue 1 239-244 
Klebanoff SJ, Agosti JM, Jörg A, Waltersdorph AM.Stimulated eosinophils release cytotoxic granule constituents, including eosinophil peroxidase (EPO) and a group of granule basic proteins (GBP). EPO reacts with H2O2 formed by the respiratory burst and a halide to form cytotoxic oxidants. The relative potency of the EPO-H2O2-halide system and the GBP is considered here. Horse eosinophils were induced to degranulate, the degranulation products were separated by chromatography on Sephadex G-50 and comparable volumes of the column fractions were tested for toxicity to Escherichia coli and the schistosomula of Schistosoma mansoni in the presence ...
Surface antigens on equine sarcoid cells and normal dermal fibroblasts as assessed by xenogeneic antisera.
Research in veterinary science    March 1, 1989   Volume 46, Issue 2 172-179 
Brostroöm H, Paulie S, Perlmann P.To characterise the expression of surface antigens on equine sarcoid cells compared to normal equine fibroblasts, immune sera were produced in rabbits against transformed cells of a virus-containing sarcoid cell line (Mc-1) and normal dermal fibroblasts, respectively. The specificities of the sera were analysed by antibody-dependent cellular cytotoxicity against 51Cr-labelled target cells using human lymphocytes as effector cells. Anti-Mc-1 antiserum induced strong cytotoxicity against transformed cells of two sarcoid cell lines (Mc-1 and Bay Mc-1), whereas the cytotoxicity against transformed...
Effect of povidone-iodine on in vitro locomotion of equine neutrophils.
Equine veterinary journal    May 1, 1987   Volume 19, Issue 3 226-228 doi: 10.1111/j.2042-3306.1987.tb01387.x
Watson ED.Incubation of equine neutrophils with povidone-iodine solutions of greater than or equal to 0.2 per cent resulted in total inhibition of migration under agarose. This was caused by the cytotoxic effects of the solutions as shown by pyknosis and cell lysis. Lower concentrations of povidone-iodine, however, did not adversely affect neutrophil viability or locomotion.
The proteins of equid herpesvirus 1 (EHV 1) recognised by equine antisera and their ability to promote antibody-dependent cell-mediated cytotoxicity.
Tierarztliche Praxis. Supplement    January 1, 1987   Volume 2 47-49 
Bridges CG, Edington N.Equine sera were used to immunoprecipitate radiolabelled virus-infected cell proteins; subsequent resolution with polyacrylamide gel electrophoresis identified the EHV-1 polypeptides VP 2, 10a, 11, 13, 14, 15, 16, 20, 21 and 23a. The humoral support of ADCC by these sera was examined in vitro. Cytotoxicity could be demonstrated against both subtypes irrespective of the immunising isolate. The implications of these results are discussed.
Biochemical and functional characterization of lymphocytes from a horse with lymphosarcoma and IgM deficiency.
Comparative immunology, microbiology and infectious diseases    January 1, 1984   Volume 7, Issue 1 53-62 doi: 10.1016/0147-9571(84)90016-x
Perryman LE, Wyatt CR, Magnuson NS.Neoplastic lymphocytes from a horse with lymphosarcoma and IgM deficiency were analyzed for ability to grow in culture; surface and cytoplasmic IgM; functional activity in blastogenesis, cytoxicity, and suppressor assays; and activities of six enzymes involved in purine and pyrimidine metabolism. The cells lacked surface and cytoplasmic IgM. They had elevated activity of adenosine deaminase and reduced activity of purine nucleoside phosphorylase. Neoplastic cells were nonresponsive in blastogenesis assay and did not kill allogeneic lymphocyte target cells or YAC-1 targets in a lectin-dependent...
Effects of cytotoxic drugs on cultured equine cells in vitro.
Equine veterinary journal    October 1, 1981   Volume 13, Issue 4 251-253 doi: 10.1111/j.2042-3306.1981.tb03509.x
Doyle A, Owen LN.Sixteen cytotoxic drugs used in cancer chemotherapy in man were studied for cytopathic effect on equine fibrosarcoma, melanoma and normal equine lung cells in vitro. Three drugs, vincristine, melphalan and methotrexate, produced cytopathic effect
Leukocyte cytotoxicity in a persistent virus infection: presence of direct cytotoxicity but absence of antibody-dependent cellular cytotoxicity in horses infected with equine infectious anemia virus.
Infection and immunity    June 1, 1979   Volume 24, Issue 3 628-636 doi: 10.1128/iai.24.3.628-636.1979
Fujimiya Y, Perryman LE, Crawford TB.Antibody-dependent cellular cytotoxicity and direct cytotoxicity assays were performed with equine infectious anemia virus-infected target cells, equine leukocytes, and equine anti-equine infectious anemia virus antibody to determine whether these mechanisms play a role in controlling viral replication in equine infectious anemia. Direct cytotoxicity was observed by using peripheral blood mononuclear cells from 7 of 10 infected horses. Antibody-dependent cellular cytotoxicity was not observed. The antibody-dependent cellular cytotoxicity reaction in horses was then studied by using sheep eryth...
Detection of tumor-specific antigens in an equine sarcoid cell line.
Infection and immunity    April 1, 1974   Volume 9, Issue 4 714-718 doi: 10.1128/iai.9.4.714-718.1974
Watson RE, Larson KA.Indirect immunofluorescence and lymphocyte cytotoxicity experiments demonstrated the presence of a tumor-specific antigen(s) on the surface of cells from an equine sarcoid cell line (Mc1). Autologous serum (taken from the horse from which the Mc1 cells were derived) and sera from three other sarcoid-bearing horses revealed a similar membrane immunofluorescence when reacted with Mc1 cells, indicating the existence of cross-reacting antibodies. Results of serum colony inhibition experiments indicate that these antibodies are not cytotoxic. Incubation of Mc1 cells with autologous lymphocytes resu...