RESUMO
OBJECTIVES: Male infertility caused by exposure to heavy metals is a current global issue. Exposure to cadmium chloride (CdCl2) negatively affects the male reproductive system. Many infertile people, especially in developing countries, resort to folkloric treatment. Plukenetia conophora is used in Nigerian folk medicine to promote fertility. This study investigated the effects of Plukenetia conophora (PC) and 4H-Pyran-4-One 2,3-Dihydro-3,5-Dihydroxy-6-Methyl (DDMP) on Wistar rats with cadmium chloride-induced testicular damage. METHODS: Forty-two male Wistar rats (150-190g) were divided into seven groups (n=6) and treated daily for 54 days as follows: Controls (normal saline); CdCl2 (2mg/kg single IP dose); CdCl2 + 200 mg/kg vitamin E; CdCl2 + 100 or 200 mg/kg PC; and CdCl2 + 25 or 50 mg/kg DDMP. The rats were sacrificed 55 days after the start of the study; Samples were collected for analysis. Biochemical parameters malondialdehyde, nitric oxide, antioxidant enzymes, and proton pumps were measured by spectrophotometry. Reproductive hormones were measured using ELISA. Data were analysed using ANOVA and differences in mean values were considered significant at p<0.05. RESULTS: Significant increases in sperm count, motility, and viability were observed in the groups given CdCl2+Vitamin E, CdCl2+PC or CdCl2+DDMP as compared with the CdCl2 group. Malondialdehyde and nitric oxide levels in the groups treated with CdCl2+PC or CdCl2+DDMP decreased significantly when compared with the group given CdCl2. Significant increases were observed in antioxidant enzymes, proton pump, and testosterone in the groups treated with CdCl2+PC or CdCl2+DDMP, respectively. CONCLUSION: Plukenetia conophora alleviated male reproductive toxicity induced by cadmium chloride in Wistar rats. 4H-Pyran-4-One 2,3-Dihydro-3,5-Dihydroxy-6-Methyl present in Plukenetia conophora may be responsible for the ameliorative effects.
Assuntos
Cloreto de Cádmio/toxicidade , Euphorbiaceae , Infertilidade Masculina/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Substâncias Protetoras/uso terapêutico , Pironas/uso terapêutico , Animais , Antioxidantes/metabolismo , Sequestradores de Radicais Livres/metabolismo , Infertilidade Masculina/induzido quimicamente , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Medicina Tradicional , Extratos Vegetais/efeitos adversos , Substâncias Protetoras/efeitos adversos , Pironas/efeitos adversos , Ratos Wistar , Análise do Sêmen , Espectroscopia de Infravermelho com Transformada de Fourier , Espermatozoides/efeitos dos fármacos , Testes de ToxicidadeRESUMO
Cynara scolymus L., popularly known as artichoke, is consumed as food and used as tea infusions for pharmacological purposes to treat liver dysfunctions and other conditions. Scientific data on the safety and protective effect of artichoke in human-derived liver cells is missing. This study investigated the genotoxic and modulatory effect of a liophilized extract suspended in water of C. scolymus L. leaves. Four extract concentrations (0.62, 1.25, 2.5 and 5.0 mg/mL) were evaluated using the comet assay on human hepatocyte cultures, HepG2 cells. Genotoxicity was assessed after two treatment periods, 1 and 24 h. Antigenotoxicity was evaluated against oxidative lesions induced by hydrogen peroxide in pre-, simultaneous and post-treatment protocols. Artichoke leaves aqueous extract induced genotoxic effects in HepG2 cells after 1- and 24-h treatments. In turn, extract concentrations of 0.62, 1.25 and 2.5 mg/mL, exhibited a protective effect in pretreatment, compared to hydrogen peroxide alone. However, in simultaneous and post-treatment protocols, only the lowest concentration reduced the frequency of DNA damage induced by hydrogen peroxide. In addition, in the simultaneous treatment protocol, the highest artichoke extract concentration increased hydrogen peroxide genotoxicity. It can be concluded that artichoke is genotoxic, in vitro, to HepG2 cells, but can also modulate hydrogen peroxide DNA damage.
Assuntos
Antioxidantes/efeitos adversos , Cynara scolymus/química , Dano ao DNA , Células Hep G2/metabolismo , Estresse Oxidativo , Extratos Vegetais/efeitos adversos , Folhas de Planta/química , Antioxidantes/isolamento & purificação , Antioxidantes/metabolismo , Brasil , Linhagem Celular Tumoral , Ensaio Cometa , Cynara scolymus/crescimento & desenvolvimento , Suplementos Nutricionais/efeitos adversos , Liofilização , Células Hep G2/efeitos dos fármacos , Hepatócitos , Humanos , Peróxido de Hidrogênio/agonistas , Peróxido de Hidrogênio/antagonistas & inibidores , Peróxido de Hidrogênio/toxicidade , Testes de Mutagenicidade , Mutagênicos/química , Mutagênicos/toxicidade , Agricultura Orgânica , Oxidantes/agonistas , Oxidantes/antagonistas & inibidores , Oxidantes/toxicidade , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/metabolismo , Folhas de Planta/crescimento & desenvolvimento , Substâncias Protetoras/efeitos adversos , Substâncias Protetoras/isolamento & purificação , Substâncias Protetoras/metabolismoRESUMO
Abstract Objective: To assess clinical and laboratory data, and acute kidney injury (AKI) in HIV-infected children using and not using highly active antiretroviral therapy (HAART) prior to admission. Methods: A retrospective study was conducted with HIV-infected pediatric patients (<16 years). Children who were using and not using HAART prior to admission were compared. Results: Sixty-three patients were included. Mean age was 5.3 ± 4.27 years; 55.6% were females. AKI was observed in 33 (52.3%) children. Patients on HAART presented lower levels of potassium (3.9 ± 0.8 vs. 4.5 ± 0.7 mEq/L, p = 0.019) and bicarbonate (19.1 ± 4.9 vs. 23.5 ± 2.2 mEq/L, p = 0.013) and had a higher estimated glomerular filtration rate (102.2 ± 36.7 vs. 77.0 ± 32.8 mL/min/1.73 m2, p = 0.011) than those not on HAART. In the multivariate analysis, the use of HAART prior to the admission was a protective factor for AKI (p = 0.036; OR = 0.30; 95% CI = 0.097-0.926). Conclusion: AKI is a common complication of pediatric HIV infection. Use of HAART prior to the admission preserved glomerular filtration and was a protective factor for AKI, but increased medication side effects, such as hypokalemia and renal metabolic acidosis.
Resumo Objetivo: Avaliar dados clínicos e laboratoriais, bem como ocorrência de lesão renal aguda (LRA), em crianças HIV positivas com e sem uso de terapia antirretroviral altamente ativa (TARV) antes da admissão. Métodos: Estudo retrospectivo em pacientes pediátricos HIV positivos (< 16 anos). Foram comparadas as crianças que estavam em uso com aquelas sem uso de TARV prévia à internação. Resultados: Foram incluídos 63 pacientes, com média de 5,3 ± 4,27 anos, 55,6% do sexo feminino. LRA foi encontrada em 33 casos (52,3%). Os pacientes que usavam TARV apresentaram menores níveis de potássio (3,9 ± 0,8 vs. 4,5 ± 0,7 mEq/L, p = 0,019) e bicarbonato (19,1 ± 4,9 vs. 23,5 ± 2,2 mEq/L, p = 0,013), bem como maior taxa de filtração glomerular estimada (102,2 ± 36,7 vs. 77,0 ± 32,8 mL/min/1,73m2, p = 0,011), do que o pacientes sem TARV prévia. Na análise multivariada o uso de TARV prévia à internação foi fator protetor contra LRA (p = 0,036; RC = 0,30; IC de 95% = 0,097-0,926). Conclusão: A LRA é uma complicação comum da infecção pediátrica pelo HIV. O uso de TARV antes da internação foi associado a melhor taxa de filtração glomerular e foi fator de proteção contra LRA, porém desencadeou efeitos colaterais como hipocalemia e acidose metabólica.
Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Infecções por HIV/complicações , Terapia Antirretroviral de Alta Atividade/métodos , Injúria Renal Aguda/complicações , Potássio/sangue , Bicarbonatos/sangue , Infecções por HIV/tratamento farmacológico , Estudos Retrospectivos , Substâncias Protetoras/efeitos adversos , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Taxa de Filtração Glomerular/efeitos dos fármacosRESUMO
OBJECTIVE: To assess clinical and laboratory data, and acute kidney injury (AKI) in HIV-infected children using and not using highly active antiretroviral therapy (HAART) prior to admission. METHODS: A retrospective study was conducted with HIV-infected pediatric patients (<16 years). Children who were using and not using HAART prior to admission were compared. RESULTS: Sixty-three patients were included. Mean age was 5.3±4.27 years; 55.6% were females. AKI was observed in 33 (52.3%) children. Patients on HAART presented lower levels of potassium (3.9±0.8 vs. 4.5±0.7mEq/L, p=0.019) and bicarbonate (19.1±4.9 vs. 23.5±2.2mEq/L, p=0.013) and had a higher estimated glomerular filtration rate (102.2±36.7 vs. 77.0±32.8mL/min/1.73m2, p=0.011) than those not on HAART. In the multivariate analysis, the use of HAART prior to the admission was a protective factor for AKI (p=0.036; OR=0.30; 95% CI=0.097-0.926). CONCLUSION: AKI is a common complication of pediatric HIV infection. Use of HAART prior to the admission preserved glomerular filtration and was a protective factor for AKI, but increased medication side effects, such as hypokalemia and renal metabolic acidosis.
Assuntos
Injúria Renal Aguda/complicações , Terapia Antirretroviral de Alta Atividade/métodos , Infecções por HIV/complicações , Adolescente , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Bicarbonatos/sangue , Criança , Pré-Escolar , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Humanos , Lactente , Masculino , Potássio/sangue , Substâncias Protetoras/efeitos adversos , Estudos RetrospectivosRESUMO
Ten known meroterpenoids and the new meroterpenoid 7 were isolated from the Chilean seaweed Stypopodium flabelliforme as their acetylated derivatives. Furthermore, the known metabolite taondiol has been isolated for the first time from this species. The molecular structure of the new metabolite was determined by spectroscopic methods based on 1D- and 2D-NMR. Isolation of 7 represents a key step toward a better understanding of the biogenesis of this class of meroterpenoids. Among the meroditerpenoids isolated, stypodiol, isoepitaondiol, epitaondiol and sargaol exhibited gastroprotective activity on the HCl/Ethanol-induced gastric lesions model in mice. Regarding the mode of gastroprotective action, the activity of epitaondiol was reversed significantly when animals were pretreated with indomethacin, N-ethylmaleimide and N-nitro-l-arginine methyl ester (L-NAME) suggesting that prostaglandins, sulfhydryl groups and nitric oxide are involved in their mode of gastroprotective action. In the case of sargaol the gastroprotective activity was attenuated with indomethacin and N-ethylmaleimide, which suggests that prostaglandins and sulfhydryl groups are also involved in the mode of action using this model.
Assuntos
Antiulcerosos/isolamento & purificação , Modelos Animais de Doenças , Diterpenos/isolamento & purificação , Descoberta de Drogas , Phaeophyceae/química , Alga Marinha/química , Úlcera Gástrica/prevenção & controle , Acetilação , Animais , Antiulcerosos/efeitos adversos , Antiulcerosos/química , Antiulcerosos/uso terapêutico , Linhagem Celular , Chile , Diterpenos/efeitos adversos , Diterpenos/química , Diterpenos/uso terapêutico , Mucosa Gástrica/efeitos dos fármacos , Humanos , Camundongos , Estrutura Molecular , Oceano Pacífico , Phaeophyceae/crescimento & desenvolvimento , Polinésia , Substâncias Protetoras/efeitos adversos , Substâncias Protetoras/química , Substâncias Protetoras/isolamento & purificação , Substâncias Protetoras/uso terapêutico , Distribuição Aleatória , Alga Marinha/crescimento & desenvolvimento , Estereoisomerismo , Terpenos/efeitos adversos , Terpenos/química , Terpenos/isolamento & purificação , Terpenos/uso terapêuticoRESUMO
OBJECTIVES: To assess whether copper deficiency plays a role in the recently described cysteamine toxicity in patients with cystinosis, and to examine whether polymorphisms in copper transporters, lysyl oxidase, and/or type I procollagen genes could be responsible for the occurrence of cysteamine toxicity in a small subset of patients with cystinosis. STUDY DESIGN: Thirty-six patients with cystinosis were included: 22 with Fanconi syndrome (including 7 with cysteamine toxicity), 12 after renal transplantation, 1 receiving hemodialysis, and 1 with ocular cystinosis. Serum copper and ceruloplasmin levels and urinary copper/creatinine ratio were measured. Genes ATP7A and CTR1 (encoding copper transporters), LOX (encoding lysyl oxidase), and COL1A1 and COL1A2 (encoding type I procollagen) were analyzed in patients with (n = 6) and without (n = 5) toxicity. Fibroblast (pro)collagen synthesis was compared in patients with (n = 3) and those without (n = 2) cysteamine toxicity. RESULTS: All 22 patients with Fanconi syndrome had increased urinary copper excretion. Serum copper and ceruloplasmin levels were decreased in 9 patients, including all 7 patients with cysteamine toxicity. No specific sequence variations were associated with toxicity. All fibroblasts exhibited normal (pro)collagen synthesis. CONCLUSION: Patients with cystinosis with cysteamine toxicity demonstrate copper deficiency. This can cause decreased activity of lysyl oxidase, the enzyme that generates the aldehydes required for collagen cross-linking. Thus, copper supplementation might prevent cysteamine toxicity.
Assuntos
Cobre/deficiência , Cisteamina/efeitos adversos , Cistinose/complicações , Substâncias Protetoras/efeitos adversos , Fármacos Renais/efeitos adversos , Adenosina Trifosfatases/genética , Adolescente , Adulto , Biomarcadores/metabolismo , Proteínas de Transporte de Cátions/genética , Ceruloplasmina/metabolismo , Criança , Pré-Escolar , Colágeno/metabolismo , Colágeno Tipo I/genética , Cadeia alfa 1 do Colágeno Tipo I , Cobre/metabolismo , Transportador de Cobre 1 , ATPases Transportadoras de Cobre , Cisteamina/uso terapêutico , Cistinose/tratamento farmacológico , Cistinose/genética , Cistinose/metabolismo , Síndrome de Fanconi/complicações , Síndrome de Fanconi/tratamento farmacológico , Síndrome de Fanconi/genética , Síndrome de Fanconi/metabolismo , Feminino , Marcadores Genéticos , Humanos , Masculino , Polimorfismo Genético , Substâncias Protetoras/uso terapêutico , Proteína-Lisina 6-Oxidase/genética , Fármacos Renais/uso terapêutico , Análise de Sequência de DNA , Adulto JovemRESUMO
O objetivo deste trabalho é avaliar e comparar o efeito protetor da acetamida nas intoxicações por monofluoroacetato de sódio (MF) e por oito plantas brasileiras que causam "morte súbita" (PBCMS) (Palicourea marcgravii, P. juruana, Pseudocalymma elegans, Arrabidaea bilabiata, Amorimia (Mascagnia) rigida, M. pubiflora, Amorimia (Mascagnia) exotropica e M. aff. rigida) em ratos, bem como descrever o quadro clínico-patológico nos animais intoxicados. Foram utilizados 33 ratos da linhagem Wistar (Rattus norvegicus albinus), nove dos quais ingeriram espontaneamente folhas frescas de P. marcgravii nas doses de 2,0 e 4,0g/kg. Dois desses ratos receberam doses únicas de acetamida de 2,0 e 4,0g/kg, por via oral um minuto antes do fornecimento da planta. Outro rato recebeu 4,0g/kg de acetamida após ingerir 4,0g/kg da planta e manifestar sintomas graves. Nos experimentos com MF, foram administradas a quatro ratos doses de 4,0 e 8,0mg/kg; o intervalo de tempo entre a administração da acetamida e dos extratos concentrados ou do MF variou entre 2 a 4 horas. A dose de acetamida utilizada variou de 2,0 a 8,0g/kg. Nos experimentos com extratos concentrados das oito PBCMS, 20 ratos foram intoxicados por via oral com doses únicas ou repetidas. A acetamida, quando previamente administrada em doses suficientemente altas, evitou o aparecimento dos sinais clínicos ou morte dos animais intoxicados por MF, bem como pelas folhas frescas de P. marcgravii e com os extratos concentrados de cada uma das sete outras PBCMS utilizadas. Todos esses ratos foram novamente submetidos ao mesmo protocolo experimental, porém sem administração de acetamida. Nesses experimentos posteriores todos os ratos manifestaram sinais clínicos e morte (exceto M. aff. rigida, cuja amostra não se revelou tóxica). Todos os ratos apresentaram aurículas de leve a acentuadamente ingurgitadas e, por vezes, também as veias cava cranial e caudal. Havia moderada dilatação cardíaca direita e esquerda em três animais. O fígado de todos os animais apresentava-se de leve a acentuadamente congesto, e em alguns ratos, verificou-se evidenciação do padrão lobular. Observou-se ainda discreta a leve presença de líquido espumoso na superfície de corte dos pulmões em três ratos. O exame histopatológico evidenciou nos rins de seis dos 30 ratos leve a moderada tumefação citoplasmática dos túbulos uriníferos contornados distais e, por vezes, também nos túbulos coletores, mas somente em quatro (dois intoxicados por P. marcgravii, um por P. elegans e outro por A. exotropica) havia a clássica lesão de degeneração hidrópico-vacuolar com picnose nuclear evidente. No fígado de 26 animais havia congestão e, destes, três apresentaram estreitamento compressivo dos cordões hepáticos, oito corpúsculos de choque; em outros três, necrose focal de discreta a moderada. Observou-se ainda, de discreta a moderada vacuolização de hepatócitos em 16 animais. Este trabalho demonstra que a acetamida possui acentuado efeito protetor, capaz de prevenir os sinais clínicos e evitar a morte dos ratos intoxicados por MF, folhas frescas de P. marcgravii e extratos concentrados de outras sete PBCMS. O quadro clínico-patológico observado nos ratos intoxicados pelo MF e pelas PBCMS deste estudo, associado ao efeito protetor da acetamida, confirma que o MF é o princípio tóxico responsável pela morte dos ratos, e, por extensão, também dos bovinos que ingeriram PBCMS.(AU)
The protective effect of acetamide in poisoning by sodium monofluoroacetate (MF) and by eight Brazilian sudden death causing plants (BSDCP) (Palicourea marcgravii, P. juruana, Pseudocalymma elegans, Arrabidaea bilabiata, Amorimia (Mascagnia) rigida, M. pubiflora, Amorimia (Mascagnia) exotropica and M. aff. rigida) was studied using rats. Additionally the clinical and pathological picture of the poisoning was described. In these experiments 33 Wistar rats (Rattus norvegicus albinus) were used. Nine rats ate spontaneously the fresh leaves of P. marcgravii at amounts of 2.0 and 4.0g/kg. Two of the rats received orally single doses of acetamide (2.0 and 4.0g/kg) one minute before the plant was supplied. A third rat received 4.0g/kg of acetamide after consumption of 4.0g/kg of the plant and showed severe symptoms of poisoning. In the experiments with MF, doses of 4.0 and 8.0mg/kg were administered to four rats. The interval between the administration of either acetamide and concentrated plant extracts or MF ranged from 2 to 4 hours; the dose of acetamide ranged from 2.0 to 8.0g/ kg. In the experiments with concentrated extracts of eight BSDCP, 20 rats were orally poisoned with single or repeated doses. Acetamide, when previously administered, prevented the appearance of clinical signs and death in all of the rats poisoned by MF, as well as of the ones poisoned by fresh P. marcgravii leaves and by the concentrated extracts of each of the other BSDCP. .(AU)
Assuntos
Animais , Ratos , Substâncias Protetoras/efeitos adversos , Acetamidas/antagonistas & inibidores , Morte Súbita/veterinária , Intoxicação por Plantas/veterináriaRESUMO
In germfree mice, the administration of short-chain fatty acids (SCFA) protected the intestinal mucosa from damage produced by 1-beta-D-arabinofuranosylcytosine (Ara-C). Animals receiving SCFA and Ara-C had intestinal morphologies closer to normal than the control animals, which had severe intestinal lesions. We concluded that orally administrated SCFA reduce intestinal lesions, improving the mucosa pattern of the small intestine and colon.