RESUMO
We evaluated the effects of guanosine 5'-monophosphate (GMP)-chelated calcium and iron (CaFe-GMP) on health and egg quality in layers experimentally infected with Salmonella Gallinarum. In this study, a CaFe-GMP feed additive was added to a commercial layer feed and fed to layers over a four-week period. All were inoculated with Salmonella Gallinarum. Body weight, mortality, clinical symptoms, and poultry production including feed intake, egg production, egg loss, and feed conversion rate were observed, and Salmonella Gallinarum was re-isolated from the liver, spleen, and cecum of the layers. All tested internal organs for the CaFe-GMP additive group exhibited significantly lower re-isolation numbers of Salmonella Gallinarum and less severe pathological changes than those in the control group, indicating that the CaFe-GMP feed supplement induced bacterial clearance and increased resistance to Salmonella Gallinarum. Additionally, due to the inhibitory action of CaFe-GMP on the growth of Salmonella Gallinarum, the CaFe-GMP additive group exhibited better egg production, including a higher laying rate and fewer broken eggs. The results suggest that a 0.16% CaFe-GMP additive may help prevent salmonellosis in the poultry industry.
Assuntos
Cálcio/uso terapêutico , Suplementos Nutricionais , Guanosina Monofosfato/uso terapêutico , Ferro/uso terapêutico , Oviposição/efeitos dos fármacos , Doenças das Aves Domésticas/prevenção & controle , Salmonelose Animal/prevenção & controle , Ração Animal , Animais , Cálcio/administração & dosagem , Quelantes de Cálcio/uso terapêutico , Galinhas/microbiologia , Feminino , Guanosina Monofosfato/administração & dosagem , Ferro/administração & dosagem , Quelantes de Ferro/uso terapêutico , Doenças das Aves Domésticas/microbiologia , Salmonella , Salmonelose Animal/microbiologiaRESUMO
Employing enhanced chemiluminescence in luminol-p-iodophenol peroxidase system and coumarine-3-carboxylic acid, it was shown that guanosine-5'-monophosphate (GMP) appreciably reduces formation of H2O2 and hydroxyl radicals induced by x-ray irradiation. Using immunoenzyme assay, we revealed that GMP lowered 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) formation in DNA in vitro after irradiation. The results of survival test have shown that mice being injected intraperitoneally with GMP after irradiation with a dose of 7 Gy had better survival rate than the control mice. GMP reduced leucopoenia and thrombocytopenia in irradiated mice. Obtained results give premises that GMP may be promising therapeutic agent for treatment of radiation injuries.
Assuntos
Antioxidantes/farmacologia , Guanosina Monofosfato/farmacologia , Protetores contra Radiação/farmacologia , 8-Hidroxi-2'-Desoxiguanosina , Animais , Antioxidantes/administração & dosagem , Antioxidantes/metabolismo , Contagem de Células Sanguíneas , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Células da Medula Óssea/efeitos da radiação , Bovinos , DNA/metabolismo , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Guanosina Monofosfato/administração & dosagem , Guanosina Monofosfato/metabolismo , Masculino , Camundongos , Protetores contra Radiação/administração & dosagem , Protetores contra Radiação/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Soroalbumina Bovina/metabolismo , Análise de Sobrevida , Raios XRESUMO
It is well known that adenine-based purines exert multiple effects on pain transmission. However, less attention has been given to the potential effects of guanine-based purines (GBPs) on pain transmission. The aim of this study was to investigate the effects of intracerebroventricular (i.c.v.) guanosine and GMP on mice pain models. Mice received an i.c.v. injection of vehicle (saline or 10 muM NaOH), guanosine (5 to 400 nmol), or GMP (240 to 960 nmol). Additional groups were also pre-treated with i.c.v. injection of the A(1)/A(2A) antagonist caffeine (15 nmol), the non-selective opioid antagonist naloxone (12.5 nmol), or the 5'-nucleotidase inhibitor AOPCP (1 nmol). Measurements of CSF purine levels and cortical glutamate uptake were performed after treatments. Guanosine and GMP produced dose-dependent antinociceptive effects. Neither caffeine nor naloxone affected guanosine antinociception. Pre-treatment with AOPCP completely prevented GMP antinociception, indicating that conversion of GMP to guanosine is required for its antinociceptive effects. Intracerebroventricular administration of guanosine and GMP induced, respectively, a 180- and 1800-fold increase on CSF guanosine levels. Guanosine was able to prevent the decrease on cortical glutamate uptake induced by intraplantar capsaicin. This study provides new evidence on the mechanism of action of GBPs, with guanosine and GMP presenting antinociceptive effects in mice. This effect seems to be independent of adenosine and opioid receptors; it is, however, at least partially associated with modulation of the glutamatergic system by guanosine.
Assuntos
Analgésicos , Guanosina Monofosfato/farmacologia , Guanosina/farmacologia , Animais , Química Encefálica/efeitos dos fármacos , Capsaicina , Cromatografia Líquida de Alta Pressão , Ácido Glutâmico/metabolismo , Guanosina/administração & dosagem , Guanosina/líquido cefalorraquidiano , Guanosina Monofosfato/administração & dosagem , Guanosina Monofosfato/líquido cefalorraquidiano , Temperatura Alta , Injeções Intraventriculares , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Medição da Dor/efeitos dos fármacos , Equilíbrio Postural/efeitos dos fármacos , Desempenho Psicomotor/efeitos dos fármacos , Tempo de Reação/efeitos dos fármacosRESUMO
This study was done to examine the protective effects of cyclic guanosine monophosphate (cGMP), a second messenger of nitric oxide, for ischemia/reperfusion injury of the liver, since it is known to induce vasodilatation and to inhibit platelet aggregation. Using an experimental model of porcine liver ischemia, 8-bromoguanosine 3',5' monophosphate, a cGMP analog, was continuously administered into the portal vein before ischemia and after reperfusion 30 min for each in the cGMP group (n = 6). Saline water was administered in the same way in the control group (n = 6). The cardiac output (CO), mean arterial blood pressure (MAP), portal venous flow (PVF), hepatic arterial flow (HAF), hepatic tissue blood flow (HTBF), and hepatic tissue cGMP level were determined. Hepatic enzymes and the bile discharge were also assessed as indicators of hepatic function. The hepatic tissue cGMP level was significantly higher, and PVF, HTBF, and the bile discharge were significantly greater in the cGMP group, while there were no remarkable differences between the groups with CO, MAP, HAF, and hepatic enzymes. In conclusion, the continuous supplementation of cGMP into the portal vein was found to be beneficial for preserving both the hepatic circulation and, consequently, the hepatic function after warm ischemia of porcine liver.
Assuntos
Guanosina Monofosfato/administração & dosagem , Circulação Hepática/efeitos dos fármacos , Traumatismo por Reperfusão/prevenção & controle , Análise de Variância , Animais , GMP Cíclico/metabolismo , Modelos Animais de Doenças , Hemodinâmica/efeitos dos fármacos , Hemodinâmica/fisiologia , Injeções Intravenosas , Testes de Função Hepática , Óxido Nítrico/análise , Óxido Nítrico/metabolismo , Veia Porta , Valores de Referência , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/fisiopatologia , SuínosAssuntos
Dieta , Guanosina Monofosfato/farmacologia , Neutrófilos/fisiologia , Ácidos Nucleicos , Nucleosídeos/farmacologia , Animais , Feminino , Guanosina Monofosfato/administração & dosagem , Injeções Intraperitoneais , Lipopolissacarídeos/toxicidade , Camundongos , Camundongos Endogâmicos BALB C , Neutrófilos/efeitos dos fármacos , Nucleosídeos/administração & dosagem , Explosão Respiratória/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The comparative activity of agonists of duodenal bicarbonate secretion was studied in the anesthetized guinea pig, where the duodenal lumen was perfused with 24 mmol/l NaHCO3 to ensure active secretion of bicarbonate. Agonists were infused alone and in combination. Dibutyryl 3',5'-cyclic adenosine monophosphate, vasoactive intestinal polypeptide (VIP) and prostaglandin E2 (PGE2) were strong stimulants of bicarbonate secretion. Theophylline, dibutyryl 3',5'-cyclic guanosine monophosphate, glucagon and prostaglandin F2 alpha (PGF2 alpha) were weaker agonists, and secretin had no effect. Combinations of any two of VIP, PGE2 and glucagon depressed bicarbonate secretion, whereas combinations of PGE2 and PGF2 alpha, VIP and PGE2, and glucagon and PGF2 alpha increased bicarbonate secretion. The data indicate that cAMP and other secondary messengers may mediate duodenal bicarbonate secretion.
Assuntos
Bicarbonatos/agonistas , Duodeno/efeitos dos fármacos , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/farmacologia , Animais , Bicarbonatos/metabolismo , Dinoprosta/administração & dosagem , Dinoprosta/farmacologia , Dinoprostona/administração & dosagem , Dinoprostona/farmacologia , Relação Dose-Resposta a Droga , Interações Medicamentosas , Duodeno/metabolismo , Glucagon/administração & dosagem , Glucagon/farmacologia , Guanosina Monofosfato/administração & dosagem , Guanosina Monofosfato/farmacologia , Cobaias , Masculino , Peptídeo Intestinal Vasoativo/administração & dosagem , Peptídeo Intestinal Vasoativo/farmacologiaRESUMO
Dietary nucleotides seem to play a number of physiologic roles during early life. They are improved in the maintenance of the immune system, intestinal maturation, and lipid metabolism. Nucleotides affect the conversion of essential fatty acids into their long-chain polyunsaturated (PUFA) derivatives in both preterm and at-term newborn infants. This work examines the effect of postnatal age and dietary nucleotides on the fatty acid composition of total plasma lipids and lipid fractions in the rat. Weanling rats (21 days old) were divided into three groups. The first group was killed, and the other two groups were fed a standard semipurified diet, and the same diet supplemented with 250 mg each of CMP, UMP, AMP, GMP, and IMP per 100 g of diet for 4 weeks. Advancing postnatal age led to an increase of total plasma fatty acids, especially saturated, and PUFA of the n-6 series, whereas PUFA of the n-3 series decreased. The fatty acid profile of plasma phospholipids (PL) exhibited minor changes, although there was a tendency to show lower levels of saturates and PUFA of the n-3 series and increased levels of PUFA of the n-6 series. Cholesteryl esters showed a response similar to that of PL, although the increase in arachidonic acid (20:4n-6) was significant. For triglycerides, linoleic acid (18:2n-6) and monounsaturates increased their levels, whereas saturates decreased. Dietary nucleotides mediated a significant increase in total plasma fatty acids, namely monounsaturated fatty acids and PUFA of both n-6 and n-3 series as compared with the control group. The relative fatty acid composition of PL and cholesteryl esters was mostly unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Envelhecimento/sangue , Dieta , Ácidos Graxos/sangue , Nucleotídeos/farmacologia , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/farmacologia , Animais , Monofosfato de Citidina/administração & dosagem , Monofosfato de Citidina/farmacologia , Ácidos Graxos Insaturados/sangue , Guanosina Monofosfato/administração & dosagem , Guanosina Monofosfato/farmacologia , Inosina Monofosfato/administração & dosagem , Inosina Monofosfato/farmacologia , Masculino , Nucleotídeos/administração & dosagem , Fosfolipídeos/sangue , Ratos , Ácidos Esteáricos/sangue , Uridina Monofosfato/administração & dosagem , Uridina Monofosfato/farmacologiaRESUMO
To obtain more effective treatment with the combination of 5-fluorouracil (FUra) and guanosine 5'-monophosphate (GMP), the influence of the time interval between FUra and GMP administration and of the molar ratio of GMP to FUra on the effect on P388 murine leukemia were investigated. The antitumor activity of FUra was significantly potentiated when GMP was administered either 0-60 min before or 5 min after FUra. The potentiated increase in lifespan (ILS) was almost the same as after simultaneous injection of the two agents. Coadministration of FUra and GMP increased the antitumor activity as compared with the respective dose of FUra alone in a treatment schedule of either day 1 only or days 1-9. The multiple-dose regimen (days 1-9) was more effective than a single high-dose regimen, and a GMP/FUra molar ratio of 4 seems to achieve the best therapeutic results against P388 leukemia. Daily simultaneous administration of FUra and GMP on days 1-9 also resulted in a significant increase in the antitumor activity against L1210 Leukemia as compared with FUra alone.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia L1210/tratamento farmacológico , Leucemia P388/tratamento farmacológico , Leucemia Experimental/tratamento farmacológico , Animais , Relação Dose-Resposta a Droga , Fluoruracila/administração & dosagem , Guanosina Monofosfato/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos , Fatores de TempoRESUMO
Young healthy volunteers received a purine-free, isoenergetic formula diet over a period of 28 to 32 days. After a short time under formula diet alone 400 mg allopurinol were administered daily. After a further 10 days each volunteer received daily, in addition, either 4 g RNA, 4 g RNA-hydrolysate, 1 g guanosine-5-monophosphate (GMP), 1 or 3 g adenosine-5-monophosphate (AMP), uridine-5-monophosphate (UMP), cytidine-5-monophosphate (CMP) or adenosine, guanosine, uridine, cytidine, guanine, hypoxanthine, xanthine, cytosine and uracil. Finally the allopurinol was omitted. The renal excretion of total orotic acid (orotic acid and orotidine), uric acid and creatinine was determined daily; serum uric acid concentrations and the enzyme activities of orotidine-5-phosphate-decarboxylase (ODCase) and hypoxanthine-guanine-phosphoribosyltransferase (HGPRTase) from erythrocytes were determined every other day. The results show that RNA, RNA-hydrolysate, purine- and pyrimidine-nucleotides and -nucleotides as well as hypoxanthine, and to a lesser extent adenine, diminish allopurinol-induced orotaciduria. This is compatible with an influence of dietary purines and pyrimidines on human pyrimidine biosynthesis.
Assuntos
Purinas/administração & dosagem , Pirimidinas/biossíntese , Monofosfato de Adenosina/administração & dosagem , Alopurinol/administração & dosagem , Monofosfato de Citidina/administração & dosagem , Guanosina Monofosfato/administração & dosagem , Humanos , Hidrólise , Ácido Orótico/urina , Orotidina-5'-Fosfato Descarboxilase/metabolismo , Pirimidinas/administração & dosagem , RNA/administração & dosagem , Uridina Monofosfato/administração & dosagemRESUMO
The chemotherapeutic effect of the 5-fluorouracil (5-FU)-guanosine 5'-monophosphate (GMP) combination in various mouse tumor systems was compared with that of 5-FU monotherapy. Antitumor activity of 5-FU against L-1210 leukemia was potentiated without increasing its toxicity to the host when GMP at 30-100 mg/kg/day was injected simultaneously with 5-FU. Any time interval between the administrations of 5-FU and GMP diminished the increase in survival. Moreover, the combination of 5-FU and GMP at 100 mg/kg/day produced marked antitumor effects in the P-388 leukemia, ascites sarcoma 180, and Ehrlich ascites carcinoma systems. GMP also potentiated the antitumor activity of 5-FU in solid tumor systems (adenocarcinoma 755 and Lewis lung carcinoma) when given by intravenous injection, but not intraperitoneal injection. The therapeutic effect of 5-FU on various murine tumors was markedly potentiated by GMP at 100 mg/kg/day or less without increasing the toxicity to the host.
Assuntos
Fluoruracila/administração & dosagem , Nucleotídeos de Guanina/administração & dosagem , Guanosina Monofosfato/administração & dosagem , Neoplasias Experimentais/tratamento farmacológico , Adenocarcinoma/tratamento farmacológico , Animais , Quimioterapia Combinada , Leucemia L1210/tratamento farmacológico , Leucemia P388/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos , Fatores de TempoRESUMO
Pool size, turnover, and excretion of uric acid were investigated in three normal subjects both during purine-free, isoenergetic liquid formula diet and during additional purine administration by use of isotope dilution techniques. The fractional turnover of the uric acid pool was increased during dietary purine administration suggesting an increased total body uric acid clearance as a result of the increase in renal clearance. Fractional turnover increased more in the female subject than in males, while pool size was increased less. It can be calculated from the results obtained that endogenous uric acid synthesis is not inhibited by dietary purines.