Effects of the consumption of caffeinated and decaffeinated instant coffee beverages on oxidative stress induced by strenuous exercise in rats.

Many authors attribute the antioxidant activity of brewed coffee to its caffeine content. In addition, caffeine intake has been associated with increased performance during physical exercise. This study analyzed the in vivo effects of drinking caffeinated and decaffeinated instant coffee (8%, w/v) on oxidative stress and antioxidant enzyme activity in the anterior tibialis muscles of rats subjected to intense exercise. It was observed that exercise induced lipid peroxidation (estimated using malondialdehyde) and protein oxidation (evaluated by determining the formation of carbonyl groups) in the muscle (P < 0.05). Decaffeinated instant coffee and caffeine solution did not exhibit antioxidant activity in vivo. Caffeinated instant coffee beverage intake did not induce changes in superoxide dismutase and glutathione peroxidase activities but was able to diminish lipid and protein oxidation in the anterior tibialis muscles of rats after exercise (P < 0.05), contributing to a reduction in the oxidative stress triggered by exercise.

Buclizine crystal forms: First Structural Determinations, counter-ion stoichiometry, hydration, and physicochemical properties of pharmaceutical relevance.

Buclizine (BCZ) is a chiral synthetic piperazine derivative which has antihistaminic, anti-muscarinic and antiemetic properties, and has been reintroduced as an appetite stimulant, especially for pediatric patients. Structural information about this drug, as well as other buclizine crystalline forms (solvates, salts and co-crystals) including the BCZ free-base (BCZ-FB), is non-existent. Here, we present for the first time the crystal structure of the monohydrochloride monohydrate salt of BCZ (BCZHCl·H2O), and of its anhydrous form, BCZHCl. Interestingly, BCZHCl·H2O was obtained by recrystallization from the raw material (BCZH2Cl2) in ethanol:water solution showing that BCZ anhydrous dihydrochloride salt changes easily to a monohydrochloride monohydrate salt modification, which raise concerns about formulation quality control. BCZHCl·H2O and BCZHCl crystallize in the orthorhombic space groups (Pna21 and Pca21) belonging to the mm2 point group and are thus classified as non-centrosymmetric achiral structures (NA). Intuitively, we expect these salts to crystallize in a space group with a center of symmetry, since less than 5% of the known racemic compounds crystallize in the NA type. The crystal structures of BCZH2Cl2 and BCZ-FB were not determined, but their existence was verified by other techniques (chloride ion analysis, PXRD, HPLC, FT-IR, DSC, TGA) and by comparison of the obtained results with those found for BCZHCl. Additionally, we have also performed an evaluation of the equilibrium solubility (at six different aqueous media) and the dissolution profile of the BCZHCl salt compared to the raw material and BCZ-FB. Different equilibrium solubility values were found comparing the three forms in acidic and neutral pH ranges and all of them were insoluble at pH > 7.0. Moreover, tablets prepared with BCZH2Cl2, BCZHCl or BCZ-FB show significant differences in terms of dissolution profile.

Hepatoprotective and Antioxidant Activities of Oil from Baru Almonds (Dipteryx alata Vog.) in a Preclinical Model of Lipotoxicity and Dyslipidemia.

The oil obtained from baru (Dipteryx alata Vog.) almonds exhibits high energy value and is reported in popular medicine for the treatment of rheumatic diseases and reproductive disturbances. Although baru oil is used in domestic cuisine, the chemical characterization of this oil and its effects on lipid metabolism are still poorly understood. Therefore, this study evaluated the fatty acid (FA) profile and the effects of baru oil on liver and aorta in a murine model of dyslipidemia. The chromatographic profile of baru oil showed high levels of unsaturated FAs, especially oleic acid. Saturated FAs, such as palmitic and lignoceric acids, were found in lower amounts. Hypercholesterolemia was induced in male Wistar rats by daily administration of a lipid emulsion by gavage for 15 weeks. Biochemical and histopathological analysis were performed on serum, aorta, and liver. The results demonstrated that animals developed marked hypercholesterolemia, liver steatosis, and increased lipid peroxidation in the aorta. Treatment with baru oil attenuated lipid peroxidation and drastically reduced liver damage, especially ballooning degeneration and steatosis. By restricting vascular and hepatic injury, this oil showed potential applicability as a functional food, reinforcing its use in popular medicine and domestic cuisine.

Pharmacokinetics and pharmacodynamics of glimepiride polymorphs.

Glimepiride (GLIM) is used as an oral antihyperglycemic agent for treatment of type 2 diabetes. The drug presents two polymorphic forms (GLIM form I and GLIM form II) described in the literature, and according to in vitro data, GLIM form II is about 3.5 times more soluble and releases 2 times the drug amount than GLIM form I in the physiological pH range. Considering the literature in vitro data and that the diabetes treatment demands glycemic control, avoiding abrupt fluctuations in the blood glucose levels, this work aimed to study the impact of GLIM polymorphism in the in vivo performance of GLIM solid oral dosages. For this, hard gelatin capsules with GLIM form I or II were prepared and orally administered in rats. After that, pharmacokinetic studies were performed by sampling animal blood at different times, and biochemical parameters (pharmacodynamic), such as glucose and insulin, were also evaluated. Our results showed that the in vitro data corroborate with our in vivo assays. GLIM form II provided higher plasma concentration of drug than form I (at baseline up to approximately 200 min after oral administration) and, consequently, increased insulin release and reduced levels of glucose, showing good correlation between pharmacokinetic and pharmacodynamics assays. Thus, this study demonstrated that GLIM polymorphs in oral dosages might alter the drug efficacy, which may expose the patients to risks, such as hypoglycemia.

Assessment of exposure to pesticides in rural workers in southern of Minas Gerais, Brazil.

The aim of the study was to assess of occupational exposure to pesticides in rural workers using genotoxicity test, bioindicators and clinical evaluation. Blood, urine and buccal samples from persons, rural workers exposed to a complex mixture of pesticides with organophosphates (n=94) and without organophosphates (n=94) were collected to compare the activities of cholinesterases, the levels of urinary dialkyl phosphates, genotoxicity data, from a cytome assay. Biomarkers were analysed by traditional/published methods Control group consisted of 50 other persons, non- occupationally exposed to pesticides from the city of Alfenas, Minas Gerais, Brazil. All subjects underwent a clinical evaluation. In the group exposed to organophosphates, the activity of acetylcholinesterase, butyrylcholinesterase and total cholinesterase was lower by 63.8%, 12.8%, and 14.8%, respectively, and 92.6% of the group had dialkyl phosphates present in their urine. The cytome assay was used to measure biomarkers of DNA damage (micronuclei and/or elimination of nuclear material by budding), cytokinetic defects (binucleated cells), and proliferative potential (basal cell) and/or cell death (condensed chromatin, karyorrhectic, pyknotic, and karyolytic cells). The group exposed to organophosphates showed significant changes in all these parameters compared to the control group and showed significant changes in budding, condensed chromatin and karyolytic cells compared with the group non-exposed to organophosphates. Data from the clinical evaluation showed significant changes in the central nervous, respiratory and auditory systems. The studied biomarkers are able to distinguish occupational and environmental exposure to pesticides and the data showed hazardous exposure to organophosphates and afforded valuable data to estimate the risk to cancer development.

Leaf extract of Coffea arabica L. reduces lipid peroxidation and has anti-platelet effect in a rat dyslipidemia model

Abstract This study aimed to evaluate the antioxidant potential of the Coffea arabica Lineu (L.) leaf extract and its effects on platelet aggregation of dyslipidemic rats. The extract was obtained by the percolation of C. arabica L. leaves in hydroethanolic solution 70% (v/v). The mass spectrometry FIA-ESI-MS² suggested the presence of chlorogenic acid, rutin acid, and quinic acid. The DPPH• radicals scavenging capacity was demonstrated (IC50 = 0.06 mg/mL). The extract was administered to rats by gavage (300 mg/kg/day) for 56 days. Dyslipidemia was induced by administering Triton WR-1339 (300 mg/kg body weight) on the 54th day. On day 56, blood was collected by puncturing the abdominal aorta artery and the aortic artery was removed. Lipid profile, markers of renal and hepatic injury, lipid peroxidation, and platelet aggregation tests were carried out. The ingestion of extract reduced the lipid peroxidation (aorta and plasma) and platelet aggregation in dyslipidemic rats. The extract did not affect markers of renal and hepatic function as analyzed in this study, suggesting neither impaired liver nor kidney function in these animals. Therefore, our results demonstrate that the extract of leaves of C. arabica L. show antioxidant potential in vitro and in vivo as well as anti-platelet aggregation in dyslipidemic animals

Coffee intake (Coffea arabica L. ) reduces advanced glycation end product (AGEs) formation and platelet aggregation in diabetic rats

Objectives: The study aimed to determine the effect of coffee intake on AGEs formation and platelet aggregation in diabetic Wistar rats. Methods: Coffee powder samples were used to prepare a 10% beverage. Diabetes mellitus was induced in the animals by administering 2% alloxan. All animal experiments were approved by the ethics committee for animal experiments under N°. 420/2012 and 536/2013. Diabetic and non-diabetic rats were divided into 6 groups treated and untreated with coffee (7.2 mL/Kg body weight) and aminoguanidine (AGE inhibiting agent) (100 mg/Kg body weight) for 50 days. After 50 days, the animals were fasted for 12 h and anesthetized (40 mg/Kg sodium pentobarbital) intraperitoneally. Blood samples were collected from the abdominal artery puncture. Hematological parameters (red cells, hemoglobin, hematocrit and leukocyte) and glycemic and HbA1c levels were measured. AGEs quantification (spectrofluorometric method) and the platelet aggregation test (aggregation of cuvettes in a four-channel platelet aggregometer) were also conducted. The rats' renal function was evaluated by measuring serum urea and creatinine. Results: Data showed that coffee intake had no effect on the hematological parameters. Fasting glucose and HbA1c dosage were significantly higher in diabetic animals compared to non-diabetic animals (confirmed the effectiveness of inducing and maintaining diabetic status). Results showed that coffee reduced AGE formation and platelet aggregation in our animal model, not altering the animals' renal function. Conclusions: These results suggest beneficial effects on vasculopathy, a common complication in diabetic patients.

Caffeinated instant coffee prevents an increase in exercise-mediated superoxide anion production in rat peritoneal neutrophils

The present study analyzed the in vivo effects of drinking caffeinated and decaffeinated instant coffee (8% w/v) by adult male Wistar rats submitted to high-intensity exercises. The parameters used in the evaluation were the determination of the activities of NADPH oxidase, myeloperoxidase and other antioxidant enzymes present in neutrophils of rats. It was observed that exercise-induced superoxide anion production depends on the NADPH oxidase activity (estimated by the cytochrome C reduction test) in peritoneal neutrophils (p < 0.05). The intake of caffeinated and decaffeinated instant coffee beverages and of a caffeine solution to 1.67% did not induced changes in the activities of the enzymes myeloperoxidase, superoxide dismutase and glutathione peroxidase (p < 0.05). But consumption of caffeinated instant coffee drink prevented an increase in NADPH oxidase-mediated superoxide production induced by highly intense exercise in rat neutrophils. While the decaffeinated instant coffee drink or caffeine solution alone did not affect NADPH oxidase-mediated superoxide production. We suggest that this activity is associated with the chemical composition and concentration of phenolic compounds and other antioxidant substances formed during roasting. From the obtained results, it was concluded that moderate intake of caffeinated instant coffee (equivalent to a daily human consumption of 4 50-mLcups of coffee) may have beneficial effects on health, contributing to a reduction in superoxide anion generation. Therefore, more research must be conducted to elucidate the mechanism of action of caffeinated coffee on NADPH oxidase in neutrophils.