RESUMO
Cefepime (CEF) is a cephalosporin and can be administered in secondary peritonitis together with metronidazole to treat sepsis. This study aimed to develop and validate an LC-ESI-QTOF-MS method for the quantification of cefepime in the plasma and peritoneal microdialysate of healthy Wistar rats. Chromatographic separation was performed using a CLC-ODS C18 column (250 × 4.6 mm), a C18 pre-column (4 mm, 5 µm) and isocratic elution. Gallic acid was used as the internal standard. The mobile phase consisted of (A) ultrapure water (pH adjusted to 3.5) and (B) acetonitrile (80:20, v/v) at 0.8 ml/min. Quantification was performed using a mass spectrometer with electrospray ionization in positive mode to monitor ions with m/z 481.1322 (CEF) and m/z 171.0288 (IS). The method was validated for selectivity, precision, accuracy, linearity, stability, lower limit of quantification, carryover, recovery and matrix effect. Calibration was done in the ranges 1-40 and 1-100 µg/ml for the peritoneal microdialysate and plasma, respectively. Plasma extraction recovery ranged from 93.9 to 99.9%. The technique was validated and successfully applied in a pilot pharmacokinetic study for estimating the free concentration of CEF in the peritoneal microdialysate of rats for the first time.
Assuntos
Líquido Ascítico , Espectrometria de Massas em Tandem , Acetonitrilas , Animais , Cefepima , Ácido Gálico , Metronidazol , Microdiálise , Ratos , Ratos Wistar , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodos , ÁguaRESUMO
The selective synthesis of 4-alkynyloxazolones and their further applications as substrates to electrophile-promoted nucleophilic cyclization have been developed. The reaction of ynamides with terminal alkynes proceeded smoothly to give 4-alkynyloxazolones in the presence of a catalytic amount of palladium(II) acetate. The products were obtained with the sequential formation of new C-C and C-O bonds via a cascade procedure. The first step involved a carbon-oxygen bond formation, via a 5-endo-dig closure, which was confirmed by X-ray analyses of the crystalline sample. Subsequently, the reaction of 4-alkynyloxazolones with an electrophilic selenium source gave 3-phenylselanyl benzofuran derivatives via an electrophile-promoted nucleophilic cyclization.
Assuntos
Paládio , Catálise , Ciclização , Estrutura Molecular , Paládio/química , EstereoisomerismoRESUMO
The aim of this study was evaluating the effects of jabuticaba aqueous extract (JPE - 0.5 g/kg) on serum lipid levels, immune system, and oxidative stress parameters of streptozotocin-induced diabetic rats. Administration of JPE for 30 days, by gavage, was able to reduce serum levels of total cholesterol, non-high density lipoprotein (HDL) cholesterol, and triglycerides in diabetic rats. The HDL cholesterol levels increased in both diabetic and healthy rats after JPE treatment. Total leukocyte and lymphocyte counts reduced in diabetic rats, and JPE treatment prevented these diabetes mellitus (DM)-induced changes in the immune system. In addition, the induction of DM also led to dysregulation in the activity of superoxide dismutase and catalase antioxidant enzymes as well as an increase in oxidative stress markers. Treatments with JPE reduced oxidative stress and modulated antioxidant enzyme activities. These data demonstrate the potential of JPE as an adjuvant treatment option for diabetic patients. PRACTICAL APPLICATIONS: Considering that it is very common to observe dyslipidemia in diabetic patients and that these alterations, combined with the increased oxidative stress levels, also common in these patients, can lead to the development of cardiovascular diseases, JPE would be an alternative treatment adjunct to reduce these risks. In addition, although more studies are needed, JPE has the potential to improve the count of total lymphocytes and leukocytes, which could assist in improving the immune response of these patients, who also commonly have a higher risk of infectious diseases. Thus, JPE could be used by these patients, in combination with conventional treatment, in the form of a nutraceutical rich in phenolic compounds.
Assuntos
Diabetes Mellitus Experimental , Animais , Glicemia , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Humanos , Sistema Imunitário , Peroxidação de Lipídeos , Lipídeos , Estresse Oxidativo , Ratos , Estreptozocina/toxicidadeRESUMO
OBJECTIVE: This work was to evaluate the chemical constitution of the hydromethanolic (30/70 methanol-water) macerating extract obtained from the leaves of C. nutans, as well as to study the antioxidant, antimicrobial, cytotoxic, and genotoxic activity of the species. Materials and methods. Phytochemical screening, antioxidant activity (total phenolic, total flavonoid, condensed tannins content, DPPH radical, and FRAP), antibacterial activity (P. aeruginosa, B. cereus, E. epidermidis, E. coli, S. aureus, E. faecalis, P. mirabilis, Candida glabrata (clinical isolate), Candida tropicalis (clinical isolate), C. krusei (clinical isolate), and C. albicans (clinical isolate)), and oxidative stress parameters (TBARS, carbonyl protein, and DCFH) were analyzed according to the literature. Toxicity of C. nutans was evaluated using an alternative method, D. melanogaster, as well as a locomotor assay. RESULTS: The phytochemical screening test of methanolic leaves extract revealed the presence of alkaloids, coumarins, quaternary bases, phenolics, flavonoids, tannins, and free steroids. A quantitative phytochemical study indicated the total phenol (30.17 ± 1.44 mg/g), flavonoid (21.64 ± 0.66 mg/g), and condensed tannins (9.58 ± 0.99 mg/g). DPPH (345.41 ± 5.35 µg/mL) and FRAP (379.98 ± 39.25 µM FeSO4/mg sample) show to extract of C. nutans leaves an intermediate value, indicating moderate antioxidant activity of the extract. Antibacterial results revealed only a positive result (antimicrobial activity) for the hexane fraction which significantly inhibited the microorganisms E. epidermidis, C. tropicalis, C. glabrata, and C. krusei at a concentration of 1000 µg/mL. TBARS, carbonyl protein, and DCFH demonstrate that the extract has the ability to protect the cell from protein and lipid damage, as well as the inhibition of oxygen-derived radicals at the three concentrations tested: 0.1, 1, and 10 mg/mL. Regarding the toxicity of C. nutans extract against D. melanogaster, it was found that until the concentration of 15 mg/mL, the extract showed no toxicity and that the LC50 obtained was 24 mg/mL. Results show that the C. nutans extract leaves used to prevent PQ damage were effective in reducing flies' mortality and improving locomotor capacity. CONCLUSION: Our studies demonstrated for the first time that C. nutans crude leaf extract has high antioxidant capacity both in vitro and in vivo through different analysis techniques. These results make it possible to infer future applications in the pharmacological area, evidenced by the low toxicity observed in D. melanogatser, as well as the ability to neutralize different sources of RONS.