Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153470 (Spleen)
 4,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate the role of metabolism in cocaine-induced immunosuppression, diazinon and beta-ionone were administered as an esterase inhibitor and a cytochrome P-450 (P-450) inducer, respectively, to B6C3F1 female mice. When 10 or 30 mg/kg of diazinon was administered 30 min before cocaine (30 mg/kg) was administered i.p. for 7 consecutive days, the suppression of the T-dependent antibody response to sheep red blood cells was potentiated greatly when compared to the suppression by cocaine alone. Spleen and thymus weights were decreased significantly and serum glutamate-pyruvate transaminase activities were elevated dramatically when cocaine and diazinon were administered together. beta-Ionone was administered s.c. for 7 consecutive days and the P-450 activities were determined 3 days after the last administration. beta-Ionone induced cocaine N-demethylation, which is the first step in the activation of cocaine to the metabolites capable of producing hepatotoxicity, as well as P-450IA1- and P-450IIB1-specific monooxygenases. The inductive effects of beta-ionone on P-450IA1/2 and P-450IIB1/2 proteins were confirmed by using Western immunoblotting with selective monoclonal antibodies. In addition, when beta-ionone (600 mg/kg) was administered with cocaine for 7 days, the suppression of the antibody response was potentiated greatly, thymus weight was decreased significantly and serum glutamate-pyruvate transaminase was elevated. Our present results suggest that inhibition of the esterase pathway of cocaine shunts the metabolism of cocaine into an immunotoxic pathway, and that the metabolism of cocaine by P-450 may be the critical pathway for the generation of the metabolites capable of suppressing the antibody response.
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PMID:Role of metabolism by esterase and cytochrome P-450 in cocaine-induced suppression of the antibody response. 781 57

We investigated possible mechanisms of the antitumor action of gamma-(9H-purine-6-yl) thiomethyl L-glutamate (6-MPG), a water-soluble derivative of 6-MP. In the double grafted tumor system, BALB/c mice were inoculated intradermally with 10(6) cells of MethA fibrosarcoma at the right inguinal region on day 0 (the primary tumor) and later with 3 x 10(6) cells at the left on day 10 (the secondary tumor). Intraperitoneal administration of 6-MPG at a dose of 100 mg/kg/day from day 3 through 7 completely prevented growth of the secondary tumor. 6-MPG showed no effect on growth of colon 26 adenocarcinoma cells inoculated in place of the secondary MethA cells (antigen specificity). 6-MPG did not inhibit the secondary MethA growth in the BALB/c (nu/nu) mouse. The inhibitory effect of 6-MPG on the secondary tumor growth was diminished by prior treatment of the primed animals with cyclosporin A and anti-Thy antibody. Spleen cells from the tumor-bearing mice treated with 6-MPG showed a tumor-neutralizing activity (Winn assay). Treatment of the spleen cells with anti-CD8 antibody plus complement diminished the tumor-neutralizing effect but that with anti-CD4 antibody plus complement did not, indicating that CD8-positive cells are responsible for potentiation of the tumor immunity. These results suggest that the antitumor effect of 6-MPG against the secondary tumor is elicited by augmenting tumor specific T-cell production.
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PMID:Study on the mechanism of immunopotentiating antitumor effect of 6-MPG, a water-soluble derivative of 6-mercaptopurine. 928 48

Effects of the administration of gamma-(9H-purine-6-yl)thiomethyl L-glutamate (6-MPG), a water-soluble derivative of 6-mercaptopurine, on concomitant and sinecomitant immunity against the implanted MethA tumor were studied in BALB/c mice. In the concomitant immunity experiments, mice were intradermally inoculated with 1x10(5) MethA cells at the right inguinal region on day 0. In sinecomitant immunity experiments, mice were similarly inoculated on day -21, and the grown tumor was excised on day -11. Both the tumor-bearing and tumor-ectomized animals were re-inoculated with 3x10(6) MethA cells intradermally at the left inguinal region on day 10. Administration of 6-MPG (100 mg/kg, i.p.) on days 3 through 7 significantly inhibited growth of the re-inoculated tumor in both series of experiments. Cyclophosphamide, adriamycin, mitomycin C and cis-diamminedichloroplatinum (II) had no significant effect on the growth of the re-inoculated tumor in the tumor-ectomized mice. Spleen cells harvested from the 6-MPG-treated tumor-ectomized mice showed a strong tumor-neutralizing activity (Winn assay).
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PMID:Augmentation of sinecomitant immunity in mice by gamma-(9H-purine-6-yl)thiomethyl L-glutamate (6-MPG), a water-soluble derivative of 6-mercaptopurine. 947 63

Podophyllotoxin, 10(-3) (M), inhibits the respiration in vitro of rat lymph nodes, thymus, kidney, tumor, spleen, liver, brain, testis, and chicken embryo. Lymph node and spleen respiration are most sensitive, and the degree of inhibition increases with time. The injection of podophyllotoxin into tumor-bearing mice (20 mg. per kg.) causes a dramatic reduction in the respiration of tumor slices. Within 6 hours, the respiration approaches zero. Inhibition is evident 2 hours after injection of the drug. Spleen respiration is reduced 50 per cent within 6 hours. Kidney and liver respirations remain within normal limits. Marked reductions in the respiration of spleen, lymph nodes, and thymus glands of normal rats are produced by the injection of 15 mg. per kg. Thymus gland is the most sensitive of these three tissues, and its respiration is reduced 66 per cent 24 hours after injection of the drug. The injection of 0.8 microgram podophyllotoxin into the yolk sac of chicken eggs bearing 5 day embryos has no effect on the respiration of the embryo within 8 hours, although this is a sufficiently toxic dose to kill 80 per cent of the embryos (within 24 hours). Kidney respiration in the presence of acetate, glucose, alanine, and glutamate is inhibited to approximately the same degree as in the absence of added substrate. Succinate and pyruvate oxidation by rat kidney slices appear to be less sensitive. Oxidation of acetate and butyrate by rabbit kidney homogenate is more sensitive to podophyllotoxin than oxidation by rabbit kidney homogenate without added substrate. Glucose oxidation by this preparation is not inhibited by 10(-3)M podophyllotoxin. The anaerobic glycolysis of chicken embryo, rat brain, and rat testis is stimulated by 10(-5) and 10(-6)M podophyllotoxin, and is inhibited by 10(-3)M. The following enzymes are not inhibited by 10(-3)M podophyllotoxin: succinoxidase from pigeon breast muscle, choline, xanthine and tyrosine oxidase from rat liver homogenate, and leucine oxidase from Proteus vulgaris; alkaline and acid phosphatase from dog serum; adenosine triphosphatase from rat liver; choline esterase from rat brain homogenate; ribonucleodepolymerase from spleen mince and thymonucleodepolymerase from dog serum. High concentrations of podophyllotoxin do not influence the viscosity and degree of polymerization of thymonucleic acid.
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PMID:The effect of podophyllotoxin on tissue metabolism and enzyme systems. 1539 71

The present study aimed to investigate the effect and the mechanisms of Bu-zhong-yi-qi-tang (BZYQ) on Spleen-Qi deficiency rat's model using nuclear magnetic resonance (NMR) metabolomics and multivariate statistical analysis methods. The rat Spleen-Qi deficiency model was established as follows: oral administration of Radix Rhei extract, loaded swimming and starvation for 24 h. The body weight and motor behavior of the rats were measured and recorded once a week. BZYQ could significantly improve body weight and behavioral of Spleen-Qi deficiency model rats compared with the model group (P < 0.05, 0.01). After drug administration, the changes in the levels of endogenous metabolites in the spleen including decreasing lactate, taurine and hypoxanthine, increasing glutamate and scyllo-inositol compared with the model group. The metabolomics approach is an effective tool for the investigation of the pharmacologic mechanism of BZYQ and it is helpful to further research.
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PMID:[1H NMR based metabolomics study of bu-zhong-yi-qi-tang in the spleen-qi deficiency rat model]. 2551 33

We evaluated the effects of splenectomy on glucose homeostasis in obese and non-obese rats. Obesity was induced by subcutaneous injections of monosodium glutamate (MSG; 4g/kg) in neonatal rats. Control (non-obese) animals received equimolar saline. Splenectomy (SPL) was performed at 21 or 60 days of life (SPL21 and SPL60) in MSG obese and non-obese groups. Glucose tolerance, insulin resistance (IR), adiposity, histology of white adipose tissue (WAT) depots and glucose-induced insulin secretion (GIIS) in isolated pancreatic islets were evaluated at 90 days of life. In non-obese, despite of hyperphagia, the spleen ablation reduced body weight gain and energy efficiency, without changes in GIIS or IR. Slight reduction in glucose tolerance and augmented adipocyte size in subcutaneous WAT was noted in non-obese SPL21 group. In MSG-SPL21 rats was observed augmented body weight gain and energy efficiency, without alter adipocyte size. In contrast, MSG-SPL60 rats had lower body weight gain, reduced energy efficiency and smaller adipocyte size in WAT visceral depot in relation to MSG non-operated. Spleen ablation reduced insulin plasma levels in the MSG-SPL21 and MSG-SPL60 groups. Moreover, splenectomy reduced GIIS and improved glucose tolerance in MSG-SPL21 group. In MSG-SPL60 rats were observed reduction in IR, without changes in GIIS, despite of elevated glucokinase expression in pancreatic islets. In conclusion, spleen ablation reduces body weight in non-obese rats and slightly modifies glucose homeostasis. In contrast, in MSG-induced obesity, absence of the spleen can ameliorate glucose tolerance and reduce insulin secretion, improving insulin sensitivity.
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PMID:Splenic participation in glycemic homeostasis in obese and non-obese male rats. 3286 51