RESUMO
Safranal, isolated from saffron (Crocus sativus L.), is known to possesses neuroprotective effects. In this study, the neuroprotective potential of safranal against PC12 cell injury triggered by ischemia/reperfusion was investigated. PC12 cells were pretreated with safranal at concentration ranges of 10-160 µM for 2 h and then deprived from oxygen-glucose-serum for 6 h, followed by reoxygenation for 24 h (OGD condition). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), 2,7-dichlorofluorescin diacetate (DCF-DA), and comet assays were used to measure the extent of cellular viability, reactive oxygen substances (ROS), and DNA damage, respectively. Also, propidium iodide (PI) flow cytometry assay and western blotting of bax, bcl-2, and cleaved caspase-3 were performed for assessment of apoptosis. OGD exposure reduced the cell viability and increased intracellular ROS production, oxidative DNA damage, and apoptosis, in comparison with untreated control cells. Pretreatment with safranal (40 and 160 µM) significantly attenuated OGD-induced PC12 cell death, oxidative damage, and apoptosis. Furthermore, safranal markedly reduced the overexpression of bax/bcl-2 ratio and active caspase-3 following OGD (p < 0.05). The present findings indicated that safranal protects against OGD-induced neurotoxicity via modulating of oxidative and apoptotic responses.Graphical abstract The schematic representation of the mode of action of safranal against PC12 cells death induced by oxygen-glucose-serum deprivation and reoxygenation (OGD-R).
Assuntos
Cicloexenos/farmacologia , Fármacos Neuroprotetores/farmacologia , Terpenos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Hipóxia Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA , Glucose , Estresse Oxidativo/efeitos dos fármacos , Oxigênio , Células PC12 , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismoRESUMO
BACKGROUND: Tramalol overdose is disproportionately more common in Iran. In recent years, Tramadol overdose has become one of the most common causes of poisoning admissions to emergency departments in this country. To the best of our knowledge, there is little or no information regarding the toxicokinetic properties of Tramadol such as its half life. Given the fact that poisoning management should be based on the toxicokinetic of substances, we aimed at investigating the half life of Tramadol in man as a critical toxicokinetic variable in overdose. METHODS: Blood samples of each patient were collected on admission and repeated later. Plasma was harvested after separation from blood cells by centrifugation and quantified using HPLC method. Calculations were performed on Tramadol blood concentration quantities. FINDINGS: Demographic: Most of cases were men (81.81%). Mean (Standard Deviation (SD), min-max) age was 23 (8.142, 17-40). Serum Tramadol levels: Mean (SD, min-max) first Tramadol concentration was 786.91 (394.53, 391-1495). Mean (SD, min-max) second Tramadol concentration was 433.09 (269.63, 148-950). Mean (SD, min-max) of Tramadol half life was calculated as 9.24 hour (2.310, 4.99-13.45) Associations: Half life was associated with higher concentrations (r=0.708 Sig=0.015). CONCLUSION: We report the mean half life of tramadol in overdose to be 9.24 hours which is remarkably higher than that measured in previous pharmacokinetic studies. We also concluded that Tramadol half life is dose dependent in overdose which may explain the further consequences of severe overdoses.
Assuntos
Analgésicos Opioides/farmacocinética , Overdose de Drogas/etiologia , Tramadol/farmacocinética , Adolescente , Adulto , Analgésicos Opioides/intoxicação , Estudos Transversais , Overdose de Drogas/sangue , Feminino , Meia-Vida , Humanos , Irã (Geográfico) , Masculino , Estudos Prospectivos , Tramadol/intoxicação , Adulto JovemRESUMO
BACKGROUND: Adiponectin is an adipose tissue-derived protein with anti-inflammatory properties. Statins are a class of cholesterol-lowering drugs, widely used for treatment of cardiovascular diseases. OBJECTIVES: In the current study, we aimed to assess the effects of simvastatin on serum levels of adiponectin in patients with dyslipidemia, recruited from Ghaem Hospital, Mashhad, Iran. MATERIALS AND METHODS: A total of 102 patients with dyslipidemia were treated with simvastatin or placebo during a double-blind, cross-over, placebo-controlled trial. The adiponectin levels were measured before and after each treatment period. Seventy seven participants completed the study. RESULTS: There was a significant reduction in serum total cholesterol (approxmately 21%), low density lipoprotein-cholesterol (LDL-C) (approxmately 28%), and triglycerides (approxmately 11%), after four weeks of treatment with simvastatin (P < 0.001). CONCLUSIONS: No significant change in serum adiponectin concentrations was observed after treatment with simvastatin. This may be because of the relatively short duration of treatment and longer treatment duration may be necessary to investigation in future studies.