RESUMO
Ginger (Zingiber officinale) is a globally marketed flavoring agent and cooking spice with a long history of human health benefits. The fungicide carbendazim (CBZ) is often detected in fruits and vegetables for human nutrition and has been reported to elicit toxic effects in different experimental animal models. The present study investigated the protective effects of 6-Gingerol-rich fraction (6-GRF) from ginger on hematotoxicity and hepatorenal damage in rats exposed to CBZ. CBZ was administered at a dose of 50 mg/kg alone or simultaneously administered with 6-GRF at 50, 100, and 200 mg/kg, whereas control rats received corn oil alone at 2 mL/kg for 14 days. Hematological examination showed that CBZ-mediated toxicity to the total white blood cell (WBC), neutrophils, lymphocytes, and platelets counts were normalized to the control values in rats cotreated with 6-GRF. Moreover, administration of CBZ significantly decreased the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase as well as glutathione level in the livers and kidneys of rats compared with control. However, the levels of hydrogen peroxide (H2O2) and malondialdehyde were markedly elevated in kidneys and livers of CBZ-treated rats compared with control. The significant elevation in the plasma indices of renal and hepatic dysfunction in CBZ-treated rats was confirmed by light microscopy. Coadministration of 6-GRF exhibited chemoprotection against CBZ-mediated hematotoxicity, augmented antioxidant status, and prevented oxidative damage in the kidney and liver of rats.
Assuntos
Antioxidantes/farmacologia , Benzimidazóis/toxicidade , Carbamatos/toxicidade , Catecóis/farmacologia , Álcoois Graxos/farmacologia , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Zingiber officinale/química , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Animais , Antioxidantes/análise , Aspartato Aminotransferases/sangue , Benzimidazóis/sangue , Bilirrubina/sangue , Carbamatos/sangue , Catalase/metabolismo , Catecóis/análise , Creatinina/sangue , Determinação de Ponto Final , Álcoois Graxos/análise , Glutationa/metabolismo , Peróxido de Hidrogênio/metabolismo , Rim/metabolismo , Fígado/metabolismo , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/análise , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , gama-Glutamilciclotransferase/sangueRESUMO
For point-of-care testing of the illegal fortification of repaglinide (Rep) in natural dietary supplements, a competitive chemiluminescent immunoassay (CLIA) was established, using a horseradish peroxidase (HRP)-luminol-H2O2 system for signal amplification. Polyclonal antibodies for Rep were produced via immunization technique. Following optimization of the enzyme reaction time and concentrations of antibody and coating antigen, the method showed a limit of quantification (LOQ) of 1.0 ng/mL in PBS and limit of detection (LOD) of 8.3 ng/mL in serum and 6.0 ng/mL in blank tablets. When applied in natural dietary supplements, the method provided results consistent with those from HPLC, suggesting that the proposed method could be used for rapid screening of Rep in natural dietary supplements and detecting Rep in serum after administration.
Assuntos
Carbamatos/análise , Carbamatos/sangue , Suplementos Nutricionais/análise , Imunoensaio , Luminescência , Piperidinas/análise , Piperidinas/sangue , Cromatografia Líquida de Alta Pressão , Humanos , Limite de Detecção , Sistemas Automatizados de Assistência Junto ao LeitoRESUMO
BACKGROUND AND OBJECTIVES: St John's wort (SJW; Hypericum perforatum) has been one of the most commonly used herbal remedies for mood disorders. This study aimed to investigate the effect of SJW, a pregnane X receptor (PXR) agonist, on the pharmacokinetics and pharmacodynamics of repaglinide, a widely consumed glucose-lowering drug. METHODS: In a two-phase, randomized, crossover study with a 4-week washout period between phases, 15 healthy subjects with specific solute carrier organic anion transporter family member 1B1 (SLCO1B1) genotypes were given pretreatment with SJW 325 mg or placebo three times daily for 14 days, and a single dose of repaglinide 1 mg was administered followed by 75 g glucose at 15 minutes after repaglinide administration. RESULTS: In all subjects, SJW had no effect on the total area under the plasma concentration-time curve from time zero to infinity (AUC(∞)), the peak plasma concentration (C(max)) or the elimination half-life (t(½)) of repaglinide. In addition, SJW had no significant effect on the blood glucose-lowering and insulin-elevating effects of repaglinide. CONCLUSION: Consumption of SJW for 14 days had no clinically significant effect on the pharmacokinetics and pharmacodynamics of repaglinide.
Assuntos
Carbamatos/farmacocinética , Depressão/tratamento farmacológico , Interações Ervas-Drogas/genética , Hypericum , Hipoglicemiantes/farmacocinética , Piperidinas/farmacocinética , Extratos Vegetais/farmacocinética , Receptores de Esteroides/agonistas , Carbamatos/sangue , Carbamatos/farmacologia , Estudos Cross-Over , Sistema Enzimático do Citocromo P-450/metabolismo , Genótipo , Humanos , Hipoglicemiantes/farmacologia , Transportador 1 de Ânion Orgânico Específico do Fígado , Transportadores de Ânions Orgânicos/genética , Fitoterapia , Piperidinas/sangue , Piperidinas/farmacologia , Placebos , Extratos Vegetais/farmacologia , Receptor de Pregnano X , Receptores de Esteroides/genética , Receptores de Esteroides/metabolismo , Adulto JovemRESUMO
The effects of extracorporeal carbamylation were determined in four patients with sickle cell anemia. Treatments were carried out in clusters every 4 to 6 weeks over a 6-month period. Mean carbamylation achieved in vivo was 1.3 moles cyanate per mole of hemoglobin. The mean in vitro P50 during treatment was 22.1 mm. Hg as compared to the pretreatment value of 30 mm. Hg. Hemoglobin concentration was increased over the 6 months by 24 per cent. The treatment resulted in the stimulation of erythropoiesis. Treated cells had a prolonged survival of about 40 days, but bilirubin did not fall. Blood volume and heart size remained unchanged. Carbamylation did not appear to alter the degree of sickling at any given O2 saturation. Painful attacks continued through the treatment period with a frequency of 84 per cent and a severity-frequency index of 77 per cent of that in the control period. There was no evidence of cyanate toxicity associated with extracorporeal therapy.