Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 26
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Ethnopharmacol ; 238: 111853, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-30954613

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Fritillariae Bulbus ("Beimu" in Chinese) is a famous traditional Chinese medicine used to treat cough, expectoration and asthma for more than 2000 years, which belongs to the Fritillaria genus in Liliaceae family. Bulbs of Fritillaria cirrhosa D.Don (BFC) and bulbs of Fritillaria pallidiflora Schrenk (BFP) are two important drugs of Beimu. Due to the significant similarities in their outward appearance characters and chemical profiles, BFC has often been adulterated with BFP in Chinese Traditional Medicine markets. AIM OF THE STUDY: This study aims to compare the oral acute toxicity and the traditional pharmacological activities including antitussive, expectorant and anti-inflammatory effects between the extract of BFC and BFP, to clear and definite if the BFP can be used as a substitute of the BFC in the application of traditional medicine. MATERIALS AND METHODS: The extracts were prepared through refluxing with 80% ethanol solvent. For the acute toxicity tests, graded doses of BFP extracts and the maximum dose of BFC extracts were administered orally to mice. The animals were observed for toxic symptoms and mortality daily for 14 days. For the pharmacological activities tests, graded doses of BFP and BFC extracts were administered orally to mice. To observe the effects relieving cough, expelling phlegm and lessening the ear swelling of BFC extracts and BFP extracts through ammonia liquor inducing cough, phenol red apophlegmating in mice and the xylene-induced auricular swelling of mouse, respectively. RESULTS: In the acute toxicity study, the LD50 value of BFP in mice was calculated to be 213.57 g/kg body weight, and the maximum feasible dose (MFD) value of BFC in mice was 452.14 g/kg. Histopathological analysis has shown inflammatory cells infiltration and cells edema in liver, multinucleated giant cell proliferation in spleen, perivascular exudate and hemorrhage in lung, glomerulus atrophy in kidney of mice after oral administrations of BFP extracts. But only liver cells edema was observed in BFC group. Both BFC extract and BFP extract significantly increased latent period of cough and inhibited cough frequency in mice induced by ammonia. Besides, the two extracts also obviously enhanced mice's tracheal phenol red output in expectorant assessment and inhibited the development of ear edema in anti-inflammatory evaluation assay. CONCLUSION: To summarize, the BFP has the significant similarities in morphological characteristics, chemical profiles and traditional pharmacological activities compared with the BFC. The result of this study provide some valid scientific support for using BFP as a plant substitute of the BFC, but considering the toxicity of BFP is much higher than BFC, we don't recommend long-term oral administration of BFP or exceeding recommended dosage of Chinese Pharmacopoeia 2015.


Assuntos
Anti-Inflamatórios , Antitussígenos , Tosse/tratamento farmacológico , Edema/tratamento farmacológico , Expectorantes , Fritillaria , Extratos Vegetais , Administração Oral , Animais , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/toxicidade , Antitussígenos/uso terapêutico , Antitussígenos/toxicidade , Expectorantes/uso terapêutico , Expectorantes/toxicidade , Feminino , Rim/efeitos dos fármacos , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Medicina Tradicional Chinesa , Camundongos , Extratos Vegetais/uso terapêutico , Extratos Vegetais/toxicidade , Raízes de Plantas , Baço/efeitos dos fármacos , Baço/patologia , Testes de Toxicidade Aguda
2.
J Ethnopharmacol ; 149(1): 297-302, 2013 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-23816499

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Root of Sorghum bicolor (L.) Moench (RSB) is an herbal medicine in Traditional Chinese Medicine, still used in some rural areas in Central China as an alternative remedy to treat cough and asthma. AIM OF THE STUDY: The study was aimed at evaluating the antitussive, expectorant and bronchodilating effects of ethanol extract of RSB, support its folk use with scientific evidence, and lay a foundation for its further researches. MATERIALS AND METHODS: RSB was extracted with 80% ethanol aqueous in reflux conditions, solutions were concentrated in reduced pressure, and lyophilized in vacuum to yield the RSB extract. Antitussive evaluations were carried out with three different models including ammonia liquor induced mice cough, capsaicin induced mice cough, and citric acid induced guinea pigs cough; phenol red secretion experiments in mice were performed to evaluate the expectorant ability; bronchodilating effects were evaluated with a bronchoconstrictive challenge induced by acetylcholine chloride and histamine in guinea pigs. RESULTS: In all the three antitussive tests, treatment of RSB significantly inhibited the frequency of cough, and prolonged the cough latent period in animals. And high dose of RSB (200mg/kg in mice and 100mg/kg in guinea pigs) created therapeutic activities as good as standard antitussive drug codeine phosphate (20mg/kg). In the expectorant evaluation, 50, 100 and 200mg/kg RSB treatment had significantly increased the amount of phenol red output for 0.39, 1.18, and 1.96 folds in mice tracheas. In the bronchodilating test, RSB treatment at 100mg/kg extended the preconvulsive time for 44.84% compared with that of before treatment in guinea pigs. CONCLUSIONS: RSB is an effective alternative medicine for the treatment of cough with potent antitussive, expectorant and bronchodilating activities.


Assuntos
Antitussígenos/uso terapêutico , Broncodilatadores/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Expectorantes/uso terapêutico , Sorghum/química , Animais , Antitussígenos/isolamento & purificação , Antitussígenos/toxicidade , Broncoconstrição/efeitos dos fármacos , Broncodilatadores/isolamento & purificação , Broncodilatadores/toxicidade , Tosse/tratamento farmacológico , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/toxicidade , Etanol/química , Etnofarmacologia , Expectorantes/isolamento & purificação , Expectorantes/toxicidade , Feminino , Cobaias , Masculino , Camundongos , Camundongos Endogâmicos , Raízes de Plantas/química , Testes de Toxicidade Aguda
3.
J Anal Toxicol ; 37(5): 318-9, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23580607

RESUMO

Guaifenesin is an over-the-counter expectorant used for chest congestion and is available both in single-ingredient formulations and in combination with antihistamines, cough suppressants and decongestants. The documented side-effects of guaifenesin are generally mild. We present the case of a 23-year-old female who committed suicide by ingestion of guaifenesin along with small amounts of cetirizine, ethanol and sertraline. Approximately 2 h after ingestion, the patient experienced central nervous system depression followed by asystole. No anatomic cause of death could be determined at autopsy. The initial toxicology detected only ethanol, which was found at a concentration insufficient to cause death. Upon further analysis, guaifenesin was detected in femoral blood at 25.0 µg/mL, urine at >50.0 µg/mL, vitreous fluid at 9.2 µg/mL, brain at 17.0 µg/g and liver at 25.0 µg/g. This is the first reported human case that can be considered a death to which guaifenesin was the significant pharmacologic contributor. Guaifenesin is not detected by the primary screening methods employed by some labs and may be missed in toxicological analyses of overdoses unless specifically suspected.


Assuntos
Doenças do Sistema Nervoso Central/induzido quimicamente , Sistema Nervoso Central/efeitos dos fármacos , Expectorantes/toxicidade , Guaifenesina/toxicidade , Parada Cardíaca/induzido quimicamente , Doenças do Sistema Nervoso Central/fisiopatologia , Overdose de Drogas , Expectorantes/análise , Evolução Fatal , Feminino , Guaifenesina/análise , Parada Cardíaca/fisiopatologia , Humanos , Adulto Jovem
4.
Shock ; 34(5): 475-81, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20220565

RESUMO

There is substantial evidence that gut barrier failure is associated with distant organ injury and systemic inflammation. After major trauma or stress, the factors and mechanisms involved in gut injury are unknown. Our primary hypothesis is that loss of the intestinal mucus layer will result in injury of the normal gut that is exacerbated by the presence of luminal pancreatic proteases. Our secondary hypothesis is that the injury produced in the gut will result in the production of biologically active mesenteric lymph and consequently distant organ (i.e., lung) injury. To test this hypothesis, five groups of rats were studied: 1) uninstrumented naive rats; 2) control rats in which a ligated segment of distal ileum was filled with saline; 3) rats with pancreatic proteases placed in their distal ileal segments; 4) rats with the mucolytic N-acetylcysteine (NAC) placed in their distal ileal segments; and 5) rats exposed to NAC and pancreatic proteases in their ileal segments. The potential systemic consequences of gut injury induced by NAC and proteases were assessed by measuring the biological activity of mesenteric lymph as well as gut-induced lung injury. Exposure of the normal intestine to NAC, but not saline or proteases, led to increased gut permeability, loss of mucus hydrophobicity, a decrease in the mucus layer, as well as morphological evidence of villous injury. Although proteases themselves did not cause gut injury, the combination of pancreatic proteases with NAC caused more severe injury than NAC alone, suggesting that once the mucus barrier is impaired, luminal proteases can injure the now vulnerable gut. Because comparable levels of gut injury caused by systemic insults are associated with gut-induced lung injury, which is mediated by biologically active factors in mesenteric lymph, we next tested whether this local model of gut injury would produce active mesenteric lymph or lead to lung injury. It did not, suggesting that gut injury by itself may not be sufficient to induce distant organ dysfunction. Therefore, loss of the intestinal mucus layer, especially in the presence of intraluminal pancreatic proteases, is sufficient to lead to injury and barrier dysfunction of the otherwise normal intestine but not to produce gut-induced distant organ dysfunction.


Assuntos
Lesão Pulmonar Aguda/etiologia , Íleo/patologia , Mucosa Intestinal/patologia , Linfa/fisiologia , Muco/fisiologia , Acetilcisteína/farmacologia , Acetilcisteína/toxicidade , Animais , Translocação Bacteriana/fisiologia , Azul Evans/farmacocinética , Expectorantes/farmacologia , Expectorantes/toxicidade , Interações Hidrofóbicas e Hidrofílicas , Íleo/efeitos dos fármacos , Íleo/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Ligadura , Pulmão/metabolismo , Masculino , Mesentério , Modelos Biológicos , Pâncreas/enzimologia , Peptídeo Hidrolases/farmacologia , Permeabilidade/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Explosão Respiratória
5.
Int J Immunopathol Pharmacol ; 22(4): 919-27, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-20074455

RESUMO

Ambroxol is a widely used secretolytic agent originally developed from vasicine, a natural alkaloid found in Adhatoda vasica, extracts of which have been used to treat bronchitis, asthma, and rheumatism. We previously reported that ambroxol inhibits IgE-dependent mediator secretion from human mast cells and basophils, key effector cells of allergic inflammation. Here, the mechanisms involved in the inhibitory properties of ambroxol were assessed in comparison to other secretolytic analogues (e.g. vasicine, bromhexine, sputolysin). The results show that, in comparison to ambroxol, which reduced IgE-dependent histamine release from basophils at 10 microM-1 mM, the release of the amine was only moderately reduced by sputolysin and vasicine at 1 mM. In contrast, above 10 microM, bromhexine was found to be toxic to basophils in vitro as evidenced by induction of histamine release and reduced cell viability. In contrast, the inhibitory actions of ambroxol at concentrations below 1 mM were not toxic and entirely reversible. Ambroxol was also more potent than either sputolysin or vasicine in attenuating basophil IL-4 and IL-13 secretions, whereas bromhexine-induced suppression of de novo cytokine synthesis was due to toxic effects. Additionally, ambroxol reduced IgE-dependent p38 MAPK phosphorylation in basophils, unlike bromhexine, sputolysin and vasicine. These results clearly show that ambroxol is both more potent and effective at inhibiting IgE-dependent basophil mediator release and p38 MAPK activity than the other secretolytic analogues employed. The therapeutic potential of ambroxol as an anti-allergic agent is further underlined by these data.


Assuntos
Ambroxol/farmacologia , Antialérgicos/farmacologia , Basófilos/efeitos dos fármacos , Expectorantes/farmacologia , Liberação de Histamina/efeitos dos fármacos , Imunoglobulina E/imunologia , Alcaloides/farmacologia , Ambroxol/toxicidade , Antialérgicos/toxicidade , Basófilos/imunologia , Bromoexina/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Ditiotreitol/farmacologia , Relação Dose-Resposta a Droga , Expectorantes/toxicidade , Humanos , Interleucina-13/metabolismo , Interleucina-4/metabolismo , Fosforilação , Quinazolinas/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
6.
Drug Metab Dispos ; 35(10): 1832-9, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17639025

RESUMO

Isoline, a major retronecine-type pyrrolizidine alkaloid (PA) from the Chinese medicinal herb Ligularia duciformis, was suggested to be the most toxic known PA. Its in vitro metabolism was thus examined in rat and mouse liver microsomes, and its toxicity was compared with that of clivorine and monocrotaline after i.p. injection in mice. Isoline was more rapidly metabolized by both microsomes than clivorine and monocrotaline and converted to two polar metabolites M1 and M2, which were spectroscopically determined to be bisline (a deacetylated metabolite of isoline) and bisline lactone, respectively. Both metabolites were formed in the presence or absence of an NADPH-generating system with liver microsomes but not cytosol. Their formation was completely inhibited by the esterase inhibitors, triorthocresyl phosphate (TOCP) and phenylmethylsulfonyl fluoride, but not at all or partially by cytochrome P450 (P450) inhibitors, alpha-naphthoflavone and proadifen (SKF 525A), respectively. These results demonstrated that both metabolites were produced by microsomal esterase(s) but not P450 isozymes. The esterase(s) involved showed not only quite different activities but also responses to different inhibitors in rat and mouse liver microsomes, suggesting that different key isozyme(s) or combinations might be responsible for the deacetylation of isoline. Isoline injected i.p. into mice induced liver-specific toxicity that was much greater than that with either clivorine or monocrotaline, as judged by histopathology as well as serum alanine aminotransferase and aspartate aminotransferase levels. Isoline-induced hepatotoxicity was remarkably enhanced by the esterase inhibitor TOCP but was reduced by the P450 inhibitor SKF 525A, indicating that rodent hepatic esterase(s) played a principal role in the detoxification of isoline via rapid deacetylation in vivo.


Assuntos
Asteraceae/química , Esterases/antagonistas & inibidores , Alcaloides de Pirrolizidina/metabolismo , Alcaloides de Pirrolizidina/toxicidade , Alanina Transaminase/sangue , Animais , Antitussígenos/metabolismo , Antitussígenos/toxicidade , Aspartato Aminotransferases/sangue , Benzoflavonas/farmacologia , Inibidores das Enzimas do Citocromo P-450 , Medicamentos de Ervas Chinesas/metabolismo , Medicamentos de Ervas Chinesas/toxicidade , Esterases/metabolismo , Expectorantes/metabolismo , Expectorantes/toxicidade , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos , Microssomos Hepáticos/metabolismo , Monocrotalina/metabolismo , Monocrotalina/toxicidade , Fluoreto de Fenilmetilsulfonil/farmacologia , Proadifeno/farmacologia , Ratos , Ratos Sprague-Dawley , Tritolil Fosfatos/farmacologia
7.
Reprod Toxicol ; 17(6): 699-708, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-14613822

RESUMO

Ifosfamide, a chemotherapeutic agent with a broad spectrum of antineoplastic activity, is concurrently administered with the uroprotectant mesna to avoid the urotoxic effect. This study was undertaken to investigate possible effects of ifosfamide-mesna treatment on the testes and semen characteristics in rabbits. Sexually mature New Zealand White male rabbits received intravenously 10 weekly treatments of ifosfamide+mesna (groups A, B and C received 30, 45 or 60 mg/kg of body weight ifosfamide+6, 9 or 12 mg/kg of body weight mesna, respectively, followed by a second equal dose of mesna 4 h later); groups MA, MB and MC received mesna alone at corresponding doses; and group S received normal saline. Reproductive organ weight as well as various qualitative and quantitative parameters of testis histology (minor diameter of seminiferous tubules, the most advanced germ cell type in seminiferous tubule identified in cross sections, and the number of germ cells per stage 1 seminiferous tubule cross section) were determined 1 day and 20 weeks after the treatment period, while semen quality (sperm count, sperm morphology and sperm progressive motility) and libido were evaluated on a weekly basis. Changes were noted only in the ifosfamide+mesna treated animals. One day after treatment, reproductive organ weights were decreased in groups A-C. Major histopathological lesions were not found; however, quantitative histological endpoints were altered in groups A-C. Transient oligospermia and teratozoospermia were noted in groups B and C, while asthenozoospermia was observed in group C only. The time course of these sperm alterations suggested possible bioaccumulation and residual activity of ifosfamide. Libido remained normal. The decrease in reproductive organ weights persisted in groups B and C to 20 weeks after treatment but only one quantitative histological endpoint, the number of the round spermatids per stage 1 seminiferous tubule cross section, remained decreased in group C. These results suggest that subchronic treatment with ifosfamide-mesna suppressed spermatogenesis and epididymal sperm maturation in the rabbit. Germinal epithelium recovery was not complete because although sperm characteristics returned to pretreatment values, not all histological alterations were ameliorated.


Assuntos
Antineoplásicos Alquilantes/toxicidade , Expectorantes/toxicidade , Ifosfamida/toxicidade , Mesna/toxicidade , Sêmen/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Combinação de Medicamentos , Genitália Masculina/efeitos dos fármacos , Genitália Masculina/crescimento & desenvolvimento , Células Germinativas/efeitos dos fármacos , Masculino , Tamanho do Órgão/efeitos dos fármacos , Coelhos , Túbulos Seminíferos/efeitos dos fármacos , Túbulos Seminíferos/patologia , Comportamento Sexual Animal/efeitos dos fármacos , Contagem de Espermatozoides , Motilidade Espermática/efeitos dos fármacos , Testículo/patologia
9.
Acta Otolaryngol ; 119(6): 685-9, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10587002

RESUMO

Mesna (Mistabron) is a mucolytic substance that is also used for chemically assisted dissection during cholesteatoma surgery. The present animal study aims to evaluate its possible ototoxic side effects. To this end, the right tympanic cavity of 9 guinea pigs was filled with either 20% mesna or 10% neomycin (serving as a positive control), while the left tympanic cavity was filled with saline (serving as a negative control). One week after administration, the inner ears were dissected out and further processed for morphological evaluation by means of either interference contrast microscopy or scanning electron microscopy. No macroscopic signs of middle ear inflammation were observed in any of the ears treated. Whereas damage was obvious in all neomycin-treated specimens, the morphology of both saline- and mesna-treated inner ears was unaffected. These findings led us to conclude that, at least on a morphological basis, no indications are at hand to assume ototoxic effects of this mucolytic substance due to a single application during cholesteatoma surgery.


Assuntos
Expectorantes/toxicidade , Células Ciliadas Auditivas/efeitos dos fármacos , Mesna/toxicidade , Administração Tópica , Animais , Antibacterianos/administração & dosagem , Antibacterianos/toxicidade , Distribuição de Qui-Quadrado , Expectorantes/administração & dosagem , Feminino , Cobaias , Células Ciliadas Auditivas/ultraestrutura , Masculino , Mesna/administração & dosagem , Microscopia Eletrônica de Varredura , Neomicina/administração & dosagem , Neomicina/toxicidade , Propriedades de Superfície
10.
Mutat Res ; 395(1): 29-36, 1997 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-9465911

RESUMO

Previous studies have shown that iodinated glycerol azeo is positive in a number of in vitro mutagenicity assays including the Ames assay (TA100; TA1535), mouse lymphoma assay, Chinese hamster ovary (cytogenetic) assay and in one in vivo study, the sex-linked-recessive-lethal assay in Drosophila. Prior studies have also shown that the drug is negative in the mouse micronucleus assay. We now report that the drug is also negative for mutagenic activity in a number of other in vivo tests. Single intraperitoneal doses of 25, 125 and 250 mg/kg were without effect in the rat bone marrow chromosomal aberration assay. Single oral doses of 30, 75, 150 and 300 were negative in the rat hepatocyte DNA-repair assay. Single intraperitoneal doses of 30 and 100 mg/kg were without effect in the sister chromatid exchange (SCE) assay in the mouse. Statistically significant effects were seen at 200 and 300 mg/kg in the initial SCE assay and at 300 and 350 mg/kg in the confirmatory SCE assay. The rationale for considering the SCE results to be anomalous and thus not relative to the overall safety evaluation of the drug is presented.


Assuntos
Aberrações Cromossômicas , Glicerol/análogos & derivados , Troca de Cromátide Irmã , Animais , Medula Óssea/efeitos dos fármacos , Reparo do DNA/efeitos dos fármacos , Reparo do DNA/genética , Expectorantes/toxicidade , Feminino , Glicerol/toxicidade , Fígado/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos , Testes de Mutagenicidade , Ratos , Ratos Endogâmicos F344 , Ratos Sprague-Dawley
11.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 16(7): 390-3, 1996 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-9387729

RESUMO

One hundred and seventy children with cough were divied into two groups at random. 120 patient were treated with Zhenkeling oral liquor (ZKL group). The other 50 children were given pectoral syrup (control group). The results showed that the total effective rates of ZKL group and control group were 96.7% and 56.0% respectively, and the markedly effective rates were 80.8%, 18.0% respectively (P < 0.001). Animal experiments indicated Zhenkeling has the effect of relieving cough, reducing sputum and ameliorating asthma; their antibiotic and anti-inflammatory effects were discovered too. The dosage of Zhenkeling was 100 times as clinical dose in acute toxicity test and the dosage was 32, 16, 8 times as clinical dose in long term toxicity test respectively. No adverse action was found in these experiments.


Assuntos
Antitussígenos/uso terapêutico , Tosse/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Expectorantes/uso terapêutico , Administração Oral , Animais , Antitussígenos/toxicidade , Criança , Pré-Escolar , Medicamentos de Ervas Chinesas/toxicidade , Expectorantes/toxicidade , Feminino , Humanos , Lactente , Masculino , Camundongos , Ratos , Ratos Wistar
12.
Toxicol Appl Pharmacol ; 139(1): 128-34, 1996 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8685895

RESUMO

Sulfation of acetaminophen is a high-affinity and low-capacity conjugation pathway in rats. It is thought that sulfation becomes saturated in rats at high doses of acetaminophen because of limited availability of the active sulfate donor, 3'-phosphoadenosine 5'-phosphosulfate (PAPS), the supply of which is, in turn, limited by the availability of its precursor, inorganic sulfate. The present study was designed to determine whether a similar mechanism is responsible for capacity-limited sulfation in mice. Saturation of acetaminophen sulfation occurs in both species; however, at the maximal rate of sulfation, sulfate and PAPS concentrations were markedly decreased in rats but not in mice. Administration of sodium sulfate and the sulfate precursor N-acetylcysteine enhanced the formation of acetaminophen sulfate in rats, but not in mice. Mice exhibited lower activities of hepatic PAPS synthetic enzymes (i.e., ATP sulfurylase and APS kinase) and sulfotransferase than rats, which may in part be responsible for their lower capacity to sulfate acetaminophen. In addition, administration of acetaminophen further decreased phenolsulfotransferase activity in mice. In rats, administration of acetaminophen did not influence hepatic sulfotransferase activity. These observations suggest that while the capacity of rats to sulfate acetaminophen is limited by the availability of PAPS, in mice it is limited by sulfotransferase activity.


Assuntos
Acetaminofen/toxicidade , Fosfoadenosina Fosfossulfato/metabolismo , Acetaminofen/sangue , Acetaminofen/farmacocinética , Acetaminofen/urina , Acetilcisteína/administração & dosagem , Acetilcisteína/toxicidade , Animais , Arilsulfotransferase/metabolismo , Sítios de Ligação , Disponibilidade Biológica , Biotransformação , Catárticos/administração & dosagem , Catárticos/toxicidade , Cromatografia Líquida de Alta Pressão , Expectorantes/administração & dosagem , Expectorantes/toxicidade , Depuradores de Radicais Livres/administração & dosagem , Depuradores de Radicais Livres/toxicidade , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Ratos , Ratos Sprague-Dawley , Especificidade da Espécie , Sulfatos/administração & dosagem , Sulfatos/sangue , Sulfatos/toxicidade , Sulfatos/urina
13.
Zhongguo Zhong Yao Za Zhi ; 20(3): 176-8, inside front cover, 1995 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-7646783

RESUMO

The water, ethanol and ether extracts from Cynanchum glaucescems administrated orally showed significant antitussive effect in ammonia-induced cough model in mice. The water and ethanol extracts had obvious expectorant effect. The filtered solution of water decoction injected intraperitoneally could effectively prevent guinea pigs from asthma induced by acetulcholine and histamine mixture, and also inhibit the ear inflammation in mice caused by croton oil. All these effects showed close dose-effect relationship.


Assuntos
Antitussígenos/farmacologia , Broncodilatadores/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Expectorantes/farmacologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/toxicidade , Antitussígenos/toxicidade , Broncodilatadores/toxicidade , Medicamentos de Ervas Chinesas/toxicidade , Expectorantes/toxicidade , Feminino , Masculino , Camundongos
14.
Regul Toxicol Pharmacol ; 18(2): 169-80, 1993 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8278639

RESUMO

Carter-Wallace conducted a detailed audit and evaluation of the data available from the carcinogenicity studies with iodinated glycerol conducted in the B6C3F1 mouse and the F344/N rat by the National Toxicology Program (NTP). We conclude that there is no evidence of carcinogenicity of the compound in either the B6C3F1 mouse or the F344/N rat.


Assuntos
Carcinógenos/toxicidade , Expectorantes/toxicidade , Glicerol/análogos & derivados , Adenoma/induzido quimicamente , Adenoma/patologia , Animais , Feminino , Glicerol/toxicidade , Leucemia Monocítica Aguda/induzido quimicamente , Leucemia Monocítica Aguda/patologia , Masculino , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Vírus da Hepatite Murina , Vírus da Parainfluenza 1 Humana , Neoplasias Hipofisárias/induzido quimicamente , Neoplasias Hipofisárias/patologia , Ratos , Ratos Endogâmicos F344 , Reprodutibilidade dos Testes
15.
Arzneimittelforschung ; 42(5): 646-9, 1992 May.
Artigo em Inglês | MEDLINE | ID: mdl-1530679

RESUMO

The pharmacological activity and acute toxicity of (-)-6(S)-hydroxy-4(R)-(1-hydroxy-1-methylethyl)-1-cyclohexene-1-ethanol (CO/1408, CAS 103079-06-7), a new mucoactive drug, were evaluated. After oral and intravenous administration CO/1408 increased the pulmonary secretion of fluorescein in rats, as an index of bronchosecretogogue activity. In addition, CO/1408 markedly increased the mucociliary transport rate. In in vitro study CO/1408 did not modify the viscosity of pig gastric mucin. Acute toxicity studies showed a very low toxicity after single dose indicating a high safety level for the doses used in this report. The results obtained point out the potential usefulness of CO/1408 to ameliorate the symptoms observed in some obstructive pulmonary diseases.


Assuntos
Cicloexanóis/farmacologia , Expectorantes/farmacologia , Acetilcisteína/farmacologia , Animais , Columbidae , Cicloexanóis/toxicidade , Cicloexenos , Expectorantes/toxicidade , Feminino , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Técnicas In Vitro , Masculino , Camundongos , Camundongos Endogâmicos ICR , Mucinas/metabolismo , Depuração Mucociliar/efeitos dos fármacos , Ratos , Ratos Endogâmicos , Sistema Respiratório/efeitos dos fármacos , Sistema Respiratório/metabolismo , Suínos , Viscosidade
16.
Cancer Detect Prev ; 16(3): 173-83, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-1458507

RESUMO

Sixty-day bioassays of iodinated glycerol, trichlorfon, and acetaminophen were conducted using a leukemia transplant model in 6- to 8-week-old F344 rats to investigate the potential of these chemicals to affect tumor progression. The chemicals were administered in the drinking water at doses that approximated those used in previously conducted 2-year carcinogenesis studies. Simultaneous with dose administration, half of a group of young, healthy, syngeneic rats were given subcutaneous transplants of mononuclear cells derived from spleens of leukemic donors. Variables used to quantitate tumor progression included body weight, spleen weight, white blood cell (WBC) and red blood cell (RBC) counts, packed cell volume, hemoglobin concentration, and platelet counts. Iodinated glycerol at 1.25 or 2.5 mg/ml caused a greater increase in leukocytosis in dosed transplant recipients in comparison to that experienced by undosed recipients: trichlorfon at 2.5 or 5.0 mg/ml enhanced splenomegaly and induced greater reductions in RBC parameters in dosed recipients in comparison to that experienced by undosed recipients. Acetaminophen at 3.0 and 6.0 mg/ml resulted in insignificant but dose-related increases in spleen weight and leukocytosis only in the female rat transplant recipients, as was observed in 2-year studies. Based on results from the short-term leukemia transplant model, data from 2-year carcinogenicity studies, and structure-activity considerations, exposure to iodinated glycerol and trichlorfon was more strongly associated with the expression of leukemia than exposure to acetaminophen. The potential carcinogenicity of each of these chemicals should be taken into consideration when calculating estimates of risk and decisions for their use.


Assuntos
Acetaminofen/toxicidade , Expectorantes/toxicidade , Glicerol/análogos & derivados , Leucemia Experimental/patologia , Triclorfon/toxicidade , Animais , Peso Corporal/efeitos dos fármacos , Testes de Carcinogenicidade , Modelos Animais de Doenças , Feminino , Glicerol/toxicidade , Leucemia Experimental/induzido quimicamente , Masculino , Transplante de Neoplasias , Ratos , Ratos Endogâmicos F344
17.
Farmaco Sci ; 40(2): 108-19, 1985 Feb.
Artigo em Italiano | MEDLINE | ID: mdl-3996580

RESUMO

New 2,4-dibromo-6-(N-cyclohexyl-N-methyl)aminomethylanilides of N-acetylcysteine and N-acetyl-S-carboxymethylcisteine derivatives, N-benzyloxycarbonylcysteine and N,N'-bisbenzyloxycarbonylcystine were synthesized. The compounds were tested for the expectorant activity in rabbit and mouse. N,N'-Bisbenzyloxycarbonylcystin-bis [2,4-dibromo-6-(N-cyclohexyl-N-methyl)aminomethyl]anilide (XIX) was selected for further investigations.


Assuntos
Anilidas/síntese química , Cisteína/análogos & derivados , Cistina/análogos & derivados , Expectorantes/síntese química , Anilidas/farmacologia , Anilidas/toxicidade , Animais , Fenômenos Químicos , Química , Cisteína/síntese química , Cisteína/farmacologia , Cisteína/toxicidade , Cistina/síntese química , Cistina/farmacologia , Cistina/toxicidade , Expectorantes/toxicidade , Dose Letal Mediana , Masculino , Camundongos , Camundongos Endogâmicos , Coelhos
18.
Langenbecks Arch Chir ; 362(1): 17-23, 1984.
Artigo em Alemão | MEDLINE | ID: mdl-6231439

RESUMO

Embolia cutis medicamentosa (ECM) is a rare complication after intramuscular injection of certain drugs, resulting in local necrosis of skin and muscle at the injection site. The pathogenesis is still not clear. Drugs and their effective substances, from which an ECM recently was described (depot penicilline, antirheumatic drug combinations), were injected intraarterially, periarterially, and intramuscularly into the hind legs of rats. The legs were examined macroscopically and histologically. Complete skin and muscle necrosis of the hind leg was only found after intraarterial injection of the incriminated drugs. The most important single effective substance was phenylbutazone. From the experiments it is concluded that the intraarterial injection mode is the most likely pathomechanism of lokal skin and muscle necrosis in the ECM arising from the incriminated drugs.


Assuntos
Erupção por Droga/patologia , Injeções Intra-Arteriais/efeitos adversos , Músculos/efeitos dos fármacos , Trombose/induzido quimicamente , Animais , Antibacterianos/toxicidade , Anti-Inflamatórios/toxicidade , Combinação de Medicamentos , Expectorantes/toxicidade , Injeções Intramusculares/efeitos adversos , Músculos/patologia , Necrose , Ratos , Ratos Endogâmicos
19.
Arzneimittelforschung ; 33(9): 1281-6, 1983.
Artigo em Inglês | MEDLINE | ID: mdl-6685509

RESUMO

The efficacy and toxicity of a compound containing organically bound iodine, 4-hydroxymethyl-2-indomethyl-2,3-dioxolane (domiodol), were evaluated. After oral and intravenous administration domiodol increased respiratory tract excretion indirectly measured on the basis of bronchial secretion in rats. Based on Kasé's method for quantitatively collecting respiratory tract fluid from rabbits, oral domiodol at the dose of 50-200 mg/kg induced a dose-related increase in respiratory tract fluid. In addition, oral domiodol (50 and 100 mg/kg) significantly reduced the viscosity of sputum collected quantitatively from rabbits with subacute bronchitis induced by long-term exposure to SO2 gas; the percentage decrease in viscosity was statistically correlated with the content of dry matter, protein and polysaccharides in the sputum. Domiodol had a marked cilio-excitatory effect, but did not affect experimental asthma in guinea-pigs or the respiratory resistance of anesthetized dogs. Subacute toxicity of the substance was investigated in rats. In serum biochemistry tests mean triglycerides were reduced in both sexes at dose levels higher than 32 mg/kg. Changes of T3 levels and a slight increase in thyroid weight accompanied by minimal histological alterations were observed in rats given high doses of domiodol. The majority of the changes observed were reversible after withdrawal of domiodol.


Assuntos
Dioxolanos/farmacologia , Dioxóis/farmacologia , Expectorantes/farmacologia , Resistência das Vias Respiratórias/efeitos dos fármacos , Animais , Asma/fisiopatologia , Líquidos Corporais/efeitos dos fármacos , Bronquite/fisiopatologia , Cílios/efeitos dos fármacos , Columbidae , Dioxolanos/toxicidade , Cães , Expectorantes/toxicidade , Feminino , Cobaias , Masculino , Coelhos , Ratos , Ratos Endogâmicos , Sistema Respiratório/efeitos dos fármacos , Escarro/efeitos dos fármacos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA