RESUMO
Traumatic brain injury (TBI) is one of the leading causes of death worldwide. There are currently no effective treatments for TBI, and trauma survivors suffer from a variety of long-lasting health consequences. With nutritional support recently emerging as a vital step in improving TBI patients' outcomes, we sought to evaluate the potential therapeutic benefits of nutritional supplements derived from bovine thymus gland, which can deliver a variety of nutrients and bioactive molecules. In a rat model of controlled cortical impact (CCI), we determined that animals supplemented with a nuclear fraction of bovine thymus (TNF) display greatly improved performance on beam balance and spatial memory tests following CCI. Using RNA-Seq, we identified an array of signaling pathways that are modulated by TNF supplementation in rat hippocampus, including those involved in the process of autophagy. We further show that bovine thymus-derived extracts contain antigens found in neural tissues and that supplementation of rats with thymus extracts induces production of serum IgG antibodies against neuronal and glial antigens, which may explain the enhanced animal recovery following CCI through possible oral tolerance mechanism. Collectively, our data demonstrate, for the first time, the potency of a nutritional supplement containing nuclear fraction of bovine thymus in enhancing the functional recovery from TBI.
Assuntos
Lesões Encefálicas Traumáticas , Extratos do Timo , Humanos , Ratos , Animais , Bovinos , Extratos do Timo/farmacologia , Extratos do Timo/uso terapêutico , Lesões Encefálicas Traumáticas/tratamento farmacológico , Neurônios , Neuroglia , Hipocampo , Modelos Animais de DoençasRESUMO
Recurrent infection with human alphaherpesvirus 1 (HHV-1) may be associated with immune exhaustion that impairs virus elimination. Thymic peptides enhance immune function and thus could overcome immune exhaustion. In this study, we investigated whether reactivation of herpes infections was associated with immune exhaustion. Moreover, we examined the impact of treatment with thymostimulin on the expression of programmed cell death protein 1 (PD-1) and its ligand (PD-L1) on T and B lymphocytes in patients suffering from recurrent HHV-1 reactivation. We also assessed the effector function of peripheral blood mononuclear cells (PBMCs) after stimulation with thymic peptides. We enrolled 50 women with reactivated HHV-1 infections and healthy volunteers. We measured the expression of various activation and exhaustion markers on the surface of PBMCs using flow cytometry. In ex vivo experiments, we measured the secretion of inflammatory cytokines by PBMCs cultured with thymostimulin. Compared with controls, patients with reactivated HHV-1 infections had increased percentages of CD3+ co-expressing CD25, an activation marker (p < 0.001). Moreover, these patients had increased percentages of CD4+ and CD8+ cells co-expressing the inhibitory markers PD-1 and PD-L1. In cultures of PBMCs from the patients, thymostimulin increased the secretion of interferon gamma (p < 0.001) and interleukin (IL)-2 (p = 0.023), but not IL-4 or IL-10.Two-month thymostimulin therapy resulted in no reactivation of HHV-1 infection during this period and the reduction of PD-1 and PD-L1 expression on the surface of T and B lymphocytes (p < 0.001). In conclusion, reactivation of herpes infection is associated with immune exhaustion, which could be reversed by treatment with thymic peptides.
Assuntos
Adjuvantes Imunológicos/uso terapêutico , Herpes Simples/tratamento farmacológico , Herpesvirus Humano 1/efeitos dos fármacos , Infecção Latente/tratamento farmacológico , Extratos do Timo/uso terapêutico , Adjuvantes Imunológicos/farmacologia , Adulto , Antivirais/farmacologia , Antivirais/uso terapêutico , Células Cultivadas , Citocinas/imunologia , Feminino , Herpes Simples/imunologia , Herpesvirus Humano 1/imunologia , Humanos , Infecção Latente/imunologia , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/imunologia , Extratos do Timo/farmacologiaRESUMO
We studied the effects of tactivin and splenic polypeptides on learning and memory of thymectomized animals. In 3-week rats, thymectomy blocked active avoidance conditioning. Injections of tactivin (0.5 mg/kg) during 1 month after surgery restored learning capacity; splenic polypeptides were ineffective.
Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Memória/efeitos dos fármacos , Nootrópicos/farmacologia , Peptídeos/farmacologia , Timectomia , Extratos do Timo/farmacologia , Timo/química , Animais , Aprendizagem da Esquiva/fisiologia , Condicionamento Clássico/fisiologia , Memória/fisiologia , Nootrópicos/isolamento & purificação , Especificidade de Órgãos , Peptídeos/isolamento & purificação , Ratos , Ratos Wistar , Baço/química , Extratos do Timo/isolamento & purificação , Timo/fisiologia , Timo/cirurgiaRESUMO
OBJECTIVE: Our aim was to investigate the influence of thymic polypeptides on pain sensitivity and to analyze a possible role of the opioid system in the implementation of the analgesia caused by immobilization stress. METHODS: The study was performed on male Wistar rats at the Moscow state University named after M. V. Lomonosov. We studied effects of thymus peptides: thymuline (0.15 mg/kg), fraction 5 thymosin (0.25 microgram/kg) and cattle thymus extracted product (CTEP) (0.5 mg/kg) on pain sensitivity in rats using test "tail flick" without stress, with acute (3 h) and sub acute (12 h) immobilization stress. The comparison groups were animals treated with saline and spleen polypeptides. RESULTS: It is shown that preparations of thymus increase the threshold of pain sensitivity in the intact animals. Immobilization stress duration 3 and 12 h in thymus peptides treated rats caused a less pronounced increase in pain threshold than in the control groups (immobilization stress 3 h: CTEP--p = 0.025, thymuline--p = 0.022, fraction 5 thymosin--p = 0.033; immobilization stress 12 h: CTEP--p = 0.034, thymuline--p = 0.027, fraction 5 thymosin--p = 0.036). The opioid receptor blocker naloxone (1 mg/kg) did not completely block the stress-induced analgesia, indicating the presence of both opioid and non -opioid components in this state. In thymus peptides treated rats, opioid component was less pronounced than in the control groups (CTEP--p = 0.031, thymuline--p = 0.026, fraction 5 thymosin--p = 0.029). CONCLUSION: Pre-activation of the opioid system by the thymus polypeptides leads to an increase in the share of non-opioid component of the stress-induced analgesia and prevents the depletion of the opioid system in immobilization stress.
Assuntos
Naloxona/farmacologia , Dor , Restrição Física/efeitos adversos , Fator Tímico Circulante , Timosina , Timo/metabolismo , Analgesia/métodos , Animais , Bovinos , Masculino , Modelos Animais , Antagonistas de Entorpecentes/farmacologia , Dor/diagnóstico , Dor/tratamento farmacológico , Dor/etiologia , Dor/metabolismo , Dor/fisiopatologia , Manejo da Dor , Ratos , Ratos Wistar , Receptores Opioides/metabolismo , Fator Tímico Circulante/metabolismo , Fator Tímico Circulante/farmacologia , Timosina/metabolismo , Timosina/farmacologia , Extratos do Timo/metabolismo , Extratos do Timo/farmacologiaRESUMO
AIM: The objective of this project was to explore the influence of immunoactive drugs (tactivin, thymulin, and thymosin fraction 5) on the development of the passive avoidance conditioned reflex. MATERIALS AND METHODS: Two types of passive avoidance boxes were used--a regular two-chamber box and a modified three-chamber box, comprising a dark chamber in which rats were exposed to electrical shock, a safe dark chamber, and a light chamber in the center. RESULTS: The project has established that the memory trace persists longer under the influence of the immunoactive drugs in both models, which is consistent with the reference nootropic piracetam test results. Notably, the immunoactive drugs' mnemotropic effect was more pronounced in the modified three-chamber box than in the standard two-chamber box. Using the modified box helped to establish the influence of tactivin, thymulin, and thymosin fraction 5 on the spatial memory component. Immunotropic preparations from thymus caused the animals to select the safe chamber 24 hours later and in subsequent tests. CONCLUSION: The project's results indicate that the drugs tested do possess mnemotropic properties, so their range of clinical use can be broadened.
Assuntos
Adjuvantes Imunológicos/farmacologia , Aprendizagem da Esquiva , Condicionamento Clássico , Memória , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Aprendizagem da Esquiva/fisiologia , Condicionamento Clássico/efeitos dos fármacos , Condicionamento Clássico/fisiologia , Reação de Fuga/efeitos dos fármacos , Reação de Fuga/fisiologia , Masculino , Memória/efeitos dos fármacos , Memória/fisiologia , Modelos Biológicos , Peptídeos/farmacologia , Ratos , Ratos Wistar , Fator Tímico Circulante/farmacologia , Timosina/análogos & derivados , Timosina/farmacologia , Extratos do Timo/farmacologiaAssuntos
Analgésicos/farmacologia , Aprendizagem da Esquiva/efeitos dos fármacos , Peptídeos/farmacologia , Receptores Opioides/metabolismo , Extratos do Timo/farmacologia , Adjuvantes Imunológicos/farmacologia , Animais , Masculino , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Ratos , Ratos Wistar , Receptores Opioides/agonistasRESUMO
It is established in experiments on noninbred rats that the use of imunofan (20 mg/kg daily) and polyoxidonium (150 mg/kg daily) for 7 days on the background of chronic intoxication with organophosphorus agent VX (0.01 LD50, single daily treatment for 30 days) resulted in almost complete recovery of phagocytic-metabolic activity of neutrophils, the content of lysozyme, cationic protein of platelet, and levels of proinflammatory cytokines TNFa, IL-1b and IL-6 in the blood. The administration of T-activin (20 mg/kg daily for 7 days) restores these parameters insignificantly. The maximum overall stimulatory effect was produced by polyoxidonium, while the minimum effect was observed for T-activin.
Assuntos
Antídotos/farmacologia , Substâncias para a Guerra Química/toxicidade , Fatores Imunológicos/farmacologia , Oligopeptídeos/farmacologia , Compostos Organotiofosforados/toxicidade , Piperazinas/farmacologia , Polímeros/farmacologia , Animais , Antídotos/uso terapêutico , Feminino , Intoxicação por Gás/tratamento farmacológico , Intoxicação por Gás/imunologia , Fatores Imunológicos/uso terapêutico , Interleucina-1beta/sangue , Interleucina-6/sangue , Masculino , Muramidase/sangue , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Oligopeptídeos/uso terapêutico , Compostos Organotiofosforados/antagonistas & inibidores , Peptídeos/farmacologia , Fagocitose/efeitos dos fármacos , Piperazinas/uso terapêutico , Polímeros/uso terapêutico , Ratos , Extratos do Timo/farmacologia , Fator de Necrose Tumoral alfa/sangueRESUMO
Apart from restoration of disordered immunological parameters, tactivin and derinat exhibit a pronounced effect on the higher integrative functions of the brain. Experiments on Wistar rats have shown that these drugs accelerated conditioning of food and defense responses. New methods for quantitative evaluation of memory trace consolidation are proposed.
Assuntos
Fatores Imunológicos/farmacologia , Aprendizagem/efeitos dos fármacos , Memória/efeitos dos fármacos , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/fisiologia , DNA/farmacologia , Masculino , Peptídeos/farmacologia , Ratos , Ratos Wistar , Extratos do Timo/farmacologiaRESUMO
In order to determine the effect of apoptosis and necrosis on the intensity of the muscular phase of infection by Trichinella spiralis, male CFW mice were orally infected with T. spiralis larvae and treated with some immunomodulating drugs: calf thymus extract (TFX), lipopolysaccharide from Escherichia coli (LPS), and dexametasone (DEX). Treatment with TFX increased the proportion of apoptotic lymphocytes and decreased the proportion of necrotic lymphocytes from 14 to 60 days after infection in mice infected with T. spiralis. Treatment with LPS increased proportions of both apoptotic and necrotic lymphocytes from 21 to 60 days after infection, especially at 28 days after infection. Treatment with DEX increased the proportion of apoptotic lymphocytes only at 28 days after infection, and significantly increased the proportion of necrotic lymphocytes at 21 days after infection. Parasite load in the affected muscle tissue was significantly lower than the control in mice treated with TFX, not significantly different from the control in mice treated with LPS, and significantly higher than the control in mice treated with DEX. The results of the study suggest that the parasite made an effort to reduce the effectivity of the host immune response in order to ensure its own survival.
Assuntos
Imunossupressores/farmacologia , Inflamação/metabolismo , Linfócitos/fisiologia , Músculo Esquelético/patologia , Trichinella spiralis , Triquinelose/patologia , Animais , Apoptose , Bovinos , Dexametasona/administração & dosagem , Dexametasona/farmacologia , Imunossupressores/administração & dosagem , Lipopolissacarídeos/administração & dosagem , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Músculo Esquelético/parasitologia , Necrose , Extratos do Timo/administração & dosagem , Extratos do Timo/farmacologia , Triquinelose/parasitologiaRESUMO
The action of the immunocorrective agent tactivin on CNS functional activity was studied in an experiment using outbred white rats. The drug was shown to affect the animals' behaviour in an elevated cross-shaped maze including learning capacity and ability to overcome functional disorders of conditioned active avoidance response. The data obtained suggest anti-stress activity of tactivin.
Assuntos
Adjuvantes Imunológicos/farmacologia , Aprendizagem da Esquiva/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Peptídeos/farmacologia , Extratos do Timo/farmacologia , Animais , Masculino , RatosRESUMO
BACKGROUND: Congaplex and Immuplex are dietary supplements that have been traditionally used to support immune system function. The purpose of these experiments was to determine whether Congaplex and Immuplex affect immune function using primary and immortalized T lymphocytes. METHODS: Immortalized CEM and Jurkat T lymphocytes and primary peripheral mononuclear blood cells (PBMCs) were treated with the aqueous extracts from Congaplex and Immuplex to determine the effects of these products on cytokine production in activated T lymphocytes. RESULTS: Congaplex enhanced phytohemagglutinin/phorbol 12-myristate 13-acetate (PHA/PMA) stimulation of both CEM and Jurkat cells as measured by the production of cytokines, while Immuplex suppressed PHA/PMA-induced production of cytokines, with the exception of interleukin (IL)-8 which was enhanced by Immuplex. In vitro treatment of PBMCs from 10 healthy donors with Congaplex or Immuplex decreased PHA-stimulated production of interferon (IFN)-gamma but increased the production of IL-13. CONCLUSIONS: While the effects of Congaplex and Immuplex differed in these two models, these data demonstrate that the aqueous extracts from these two dietary supplements can affect the inflammatory response of T lymphocytes.
Assuntos
Citocinas/biossíntese , Suplementos Nutricionais , Fatores Imunológicos/farmacologia , Fitoterapia , Linfócitos T/efeitos dos fármacos , Linhagem Celular , Combinação de Medicamentos , Humanos , Interferon gama/biossíntese , Interleucina-13/biossíntese , Interleucina-8/biossíntese , Células Jurkat , Micronutrientes/farmacologia , Fito-Hemaglutininas/farmacologia , Extratos Vegetais/farmacologia , RNA Mensageiro/biossíntese , Linfócitos T/metabolismo , Acetato de Tetradecanoilforbol/farmacologia , Extratos do Timo/farmacologiaRESUMO
BACKGROUND: We have recently demonstrated that Thymax, a gross thymic extract, induces the functional activity of human dendritic cells (DCs) in vitro. In this study, the role of Thymax in phenotypic correction of age-associated functional decline in immune cells in mice was evaluated. MATERIALS AND METHODS: C57BL/6 mice (13 months old) were treated with Thymax orally (20% v/v) for 4 weeks. Different splenic cell types, dendritic cells (DCs), B-cells, T-cells and natural killer (NK) cells, were analyzed using flow cytometry. RESULTS: Treatment with Thymax resulted in: i) a significant increase in the percentages of DCs (1.6-fold), B-cells (7-fold) and T-cells (5-fold) over the control (p<0.05); ii) an increase in the percentages of activation markers (CD25 and CD69) of CD4(+) and CD8(+) T-cells; and iii) an enhancement in NK activity. Thymax showed no adverse side-effects. CONCLUSION: Thymax might have a role in reversing immune dysfunction in the elderly.
Assuntos
Envelhecimento/imunologia , Baço/efeitos dos fármacos , Extratos do Timo/farmacologia , Animais , Antígenos CD/metabolismo , Linfócitos B/citologia , Linfócitos B/efeitos dos fármacos , Linfócitos B/metabolismo , Biomarcadores/metabolismo , Contagem de Células , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Células Dendríticas/citologia , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/metabolismo , Ingestão de Líquidos/efeitos dos fármacos , Citometria de Fluxo , Células Matadoras Naturais/citologia , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fenótipo , Baço/citologia , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismoRESUMO
BACKGROUND: We have recently demonstrated that Thymax, a gross thymic extract, induces an apoptotic effect against human breast cancer cells. In this study, the ability of Thymax to activate human dendritic cells (DCs) and the DC-directed T-cell response was examined in an in vitro culture model of peripheral blood mononuclear cells. MATERIALS AND METHODS: The level of costimulatory molecules (CD40, CD80, CD83, CD86) and T-cell proliferation were analyzed by flow cytometry. Cytokine secretion was measured by ELISA. RESULTS: Thymax activated DCs to secrete interleukin (IL)-12p40 and IL-6 cytokines and inhibited IL-10 production. Additionally, Thymax caused the up-regulation of CD80 and CD86 in DCs, leading to an increase in CD4(+) T-cells, which subsequently induced secretion of interferon-gamma (IFN-gamma). CONCLUSION: Taken together, the data showed that Thymax activated DCs and, consequently, Th1 cells. Thus, Thymax is an immune-activating compound that needs to be evaluated extensively for its possible therapeutic properties.
Assuntos
Células Dendríticas/efeitos dos fármacos , Leucócitos Mononucleares/efeitos dos fármacos , Extratos do Timo/farmacologia , Antígenos CD/biossíntese , Antígenos CD/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Células Cultivadas , Citocinas/biossíntese , Citocinas/imunologia , Células Dendríticas/citologia , Células Dendríticas/imunologia , Relação Dose-Resposta Imunológica , Citometria de Fluxo , Humanos , Interferon gama/imunologia , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/imunologia , Lipopolissacarídeos/farmacologia , Ativação LinfocitáriaRESUMO
Experiments on outbred albino rats showed that tactivin (thymic polypeptide preparation) reduced functional disturbances in active avoidance reaction induced by extra electric current exposure violating the established relationships between the stimuli, reaction, and its result. The preparation provided high level of avoidance reaction after its violation. New effects of immunocorrective agent tactivin were detected. It not only restored the disordered immunological parameters, but also exhibited a pronounced effect on the higher integrative functions of the brain and produced an antistress effect.
Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Peptídeos/farmacologia , Extratos do Timo/farmacologia , Animais , Masculino , RatosRESUMO
The aim of the study was to determine the effect of thymus factor X (TFX-Jelfa) on the percentage of apoptotic and necrotic lymphocytes in the spleen, mesenteric lymph nodes, and muscle tissue of mice infected with 200 larvae of Trichinella spiralis. TFX was administered subcutaneously at a dose of 15mg/kg. On days 7, 14, 21, 28, 35, 42, and 60 after infection, apoptotic and necrotic cells were detected by flow cytometry after staining with the Annexin V-Fluos Staining Kit. TFX increased the percentage of apoptotic lymphocytes in the spleen, mesenteric lymph nodes, and muscle tissue of mice infected with T. spiralis. The effect of TFX on the percentage of necrotic lymphocytes was weaker and less clear. Parasite load was lower in infected mice treated with TFX than in the untreated control mice. The effect of TFX on the host immune response and the survival of parasite larvae was therefore probably affected by the extent of inflammatory infiltrates, and not by the percentage of lymphocytes undergoing apoptosis.
Assuntos
Apoptose/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Extratos do Timo/farmacologia , Trichinella spiralis , Triquinelose/tratamento farmacológico , Animais , Citometria de Fluxo , Linfonodos/efeitos dos fármacos , Linfonodos/patologia , Linfócitos/patologia , Masculino , Camundongos , Músculos/efeitos dos fármacos , Músculos/parasitologia , Músculos/patologia , Necrose , Baço/efeitos dos fármacos , Baço/patologia , Extratos do Timo/uso terapêutico , Trichinella spiralis/efeitos dos fármacos , Trichinella spiralis/imunologia , Trichinella spiralis/patogenicidade , Triquinelose/imunologia , Triquinelose/patologiaRESUMO
Previous studies have shown that thymic extracts possess antitumor and antimetastatic properties, but the mechanisms are not completely understood. Therefore, in this study the ability of the gross thymic extract Thymax to induce apoptosis in human breast cancer cell line (MCF-7) cells in vitro was evaluated. Tumor cells were cultured with different concentrations of Thymax for 24 h and the apoptotic response was assessed by propidium iodide and TUNEL assays. Activation of caspases and changes in mitochondrial membrane potential (MMP) were monitored by flow cytometry and the expression of Bcl-2 and Bax was determined by Western blot analysis. Thymax induced apoptosis in monolayer MCF-7 cells in a dose-dependent manner; at concentrations of 2.5, 5 and 10% (v/v) it caused 9%, 10% and 25% apoptosis, respectively, as compared to 6% for control cancer cells without treatment. The induction of apoptosis by Thymax was associated with activation of caspases 8 and 9, and the addition of a pan caspase inhibitor partially inhibited Thymax-induced apoptosis by 20%. In addition, the MMP was decreased significantly at Thymax concentrations of 5%-20%, which was associated with a decrease in the protein expression of Bcl-2 and an increase in Bax. These results suggest that Thymax exerts its effects via the mitochondrial pathway of apoptosis and may represent a new class of adjuvants for the treatment of breast cancer.
Assuntos
Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Mitocôndrias/efeitos dos fármacos , Extratos do Timo/farmacologia , Clorometilcetonas de Aminoácidos/farmacologia , Neoplasias da Mama/metabolismo , Caspase 8/metabolismo , Caspase 9/metabolismo , Inibidores de Caspase , Linhagem Celular Tumoral , Ativação Enzimática/efeitos dos fármacos , Citometria de Fluxo , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/fisiologia , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Proteína X Associada a bcl-2/biossínteseRESUMO
Investigation of the condition of higher nervous activity and immune system after the vilosen immunostimulation was conducted. It was shown that vilosen caused increase of the monocytes and T-lymphocytes quantity at the expence of T-supressors subpopulation in the peripheral blood. Increase of the functional mobility of the nervous processes was also shown. Positive correlations between the functional mobility and quantity of the monocytes (r=0,7) and T- supressors (r=0,6) quantity in the perypheral blood were established.
Assuntos
Adjuvantes Imunológicos/farmacologia , Atividade Nervosa Superior/efeitos dos fármacos , Sistema Imunitário/efeitos dos fármacos , Extratos do Timo/farmacologia , Adjuvantes Imunológicos/administração & dosagem , Administração Intranasal , Humanos , Imunidade Celular/efeitos dos fármacos , Contagem de Leucócitos , Masculino , Monócitos/efeitos dos fármacos , Linfócitos T Reguladores/efeitos dos fármacos , Extratos do Timo/administração & dosagemRESUMO
The studies were carried out on Balb/c mice exposed to restraint stress twice for 12 h at 24 h intervals. Prior to stress exposure, the mice were treated with calf thymus extract (TFX - Jelfa) i.p. at a dose of 10 mg/kg, ten times at 24 h intervals. TFX was used per se or with zinc ions interaction, by adding zinc ions (as sulfate salt) to drinking water at a dose of 72 microg/mouse per day. The results obtained show that restraint stress dramatically decreased the total number of thymocytes and splenocytes which is also accompanied by decreasing weight ratio of the thymus and spleen. The decreasing number of thymic and spleen cells corresponded to a diminishing percentage of immature, double-positive CD4+CD8+ thymocytes, mature single-positive CD4+ thymic cells and CD4+, CD8+ and CD19+ splenocytes. Changes in the number of thymic cells affect their activity, which is expressed as a decreased proliferative response of thymocytes stimulated in vitro with concanavalin A (Con A) and phytohaemagglutinin (PHA). Besides, exposure to the restraint stress decreased interleukin-1 (IL-1) production by murine intraperitoneal macrophages stimulated in vitro with lipopolisacharide (LPS) from E. coli. Previous treatment with TFX counteracted restraint stress-induced immunosuppression, which is expressed as partial normalisation of the total number of thymic and spleen cells, accelerated regeneration of these two lymphatic organs, shortned suppressive action of restraint stress on the percentage of immature CD4+CD8+ thymocytes and CD4+ splenocytes and in total normalisation of the CD4+ thymocytes and CD8+ splenocytes. TFX administered prior to restraint stress not only counteracted the suppresive effects of stress on the proliferative activity of thymic cells stimulated in vitro with Con A and PHA, but also augmented the proliferative response of these cells to two mitogens. The immunorestorative effect of TFX was augmented by zinc supplementation.
Assuntos
Imunidade Celular/efeitos dos fármacos , Estresse Fisiológico/imunologia , Extratos do Timo/farmacologia , Zinco/farmacologia , Animais , Bovinos , Feminino , Interleucina-1/biossíntese , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Mitógenos/farmacologia , Restrição Física , Baço/citologia , Timo/citologiaRESUMO
We studied the effect of combination treatment with T-activin and vitamin E on acute toxicity and antitumor activity of cyclophosphamide in mice. Combined administration of these preparations 1.37-fold increased the maximum permissible dose of cyclophosphamide without affecting its LD(50)and delayed mouse death from cyclophosphamide toxicity. Most mice died only 3 days after combination treatment with the test preparations and cyclophosphamide in doses of LD(16)-LD(84). The second peak of death from hematologic toxicity of cyclophosphamide was absent under these conditions. T-activin and vitamin E did not abolish the antitumor effect of cyclophosphamide on mice with subcutaneously implanted P-388 lympholeukemia. Tumor growth was suppressed by 100%.