Influence of Normo- and Hypogonadal Condition, Hyperuricemia, and High-Fructose Diet on Renal Changes in Male Rats

Background. There is a gender disparity in the incidence, prevalence, and progression of renal disease. The object of this paper is to evaluate the presence and type of renal lesion in normogonadic and hypogonadic male rats in a mild hyperuricemia induced condition and exposed to a high-fructose diet. Methods. 56 adult male Wistar rats were used. Animals were divided into two groups, one normogonadic (NGN) and one hypogonadic (HGN), and each group was divided into four subgroups in accordance with the treatment: control with only water (C), fructose (F), oxonic acid (OA), and fructose + oxonic acid (FOA). Renal changes were evaluated by measuring glomerulosclerosis, fibrosis, and arteriolar media/lumen (M/L) ratio. Results. The OA and FOA groups presented significantly hypertension (p<0.001). The OA group significantly increased (p<0.05) the percentage of glomerulosclerosis as well as the FOA group (p<0.001). When comparing NGN versus HGN, we observed a trend to a lower glomerulosclerosis in the latter. A higher arteriolar M/L ratio was observed in the OA (p<0.05) and FOA (p<0.001). Conclusion. Hyperuricemia conditions and a high-fructose diet favor blood pressure increase together with changes in the arteriolar media/lumen ratio and renal glomerular damage. These changes were more apparent in normogonadic animals

A Prenylated Flavanone from Dalea elegans Inhibits Rhodamine 6 G Efflux and Reverses FluconazoleResistance in Candida albicans

In previous studies, 2′,4′-dihydroxy-5′-(1′′′,1′′′-dimethylallyl)-6-prenylpinocembrin, a prenylated flavonoid isolated from Dalea elegans roots, showed activity against multiresistant Staphylococcus aureus and Candida albicans, as well as an uncoupling effect on mitochondria and antioxidant activity. The aim of this study was to evaluate the inhibitory effects of 2′,4′-dihydroxy-5′-(1′′′,1′′′-dimethylallyl)-6-prenylpinocembrin and fluconazole on the efflux of rhodamine 6 G in azole-resistant C. albicans 12–99 that expresses multidrug transporters Cdr1p, Cdr2p, and Mdr1p. The effect of fluconazole and 2′,4′-dihydroxy-5′-(1′′′,1′′′-dimethylallyl)-6-prenylpinocembrin on rhodamine 6 G efflux was assessed in both azole-sensitive and azole-resistant C. albicans. Between 1 and 1000 µM, 2′,4′-dihydroxy-5′-(1′′′,1′′′-dimethylallyl)-6-prenylpinocembrin inhibited rhodamine 6 G efflux only in azole-resistant C. albicans 12–99 in a concentration-dependent manner (IC50 = 119 µM); a competitive effect was observed. It also showed selectivity of action in comparison with other flavanones (6-prenylpinocembrin, isolated from aerial parts of D. elegans, pinocembrin, naringenin, and hesperetin, all at 250 µM). To check the possible implications of the inhibition of azole efflux on cell growth, antifungal assays were conducted. Minimal inhibitory concentration values were 150 µM for 2′,4′-dihydroxy-5′-(1′′′,1′′′-dimethylallyl)-6-prenylpinocembrin and higher than 400 µM for fluconazole. The combination of both compounds at either inhibitory or subinhibitory concentrations was significantly more effective than each compound separately. Minimal inhibitory concentration for fluconazole decreased by more than 400 times in the presence of 100 µM 2′,4′-dihydroxy-5′-(1′′′,1′′′-dimethylallyl)-6-prenylpinocembrin, reversing azole resistance and giving values similar to those of azole-sensitive C. albicans. These data are consistent with a dual action of 2′,4′-dihydroxy-5′-(1′′′,1′′′-dimethylallyl)-6-prenylpinocembrin: direct antifungal effect on azole-resistant C. albicans 12–99 and inhibition of azole transporters, which results in reversion of fluconazole resistance.Fil: Peralta, Mariana Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Calise, Maximiliano. Universidad de Buenos Aires. Facultad de Medicina. Cátedra de Farmacología; ArgentinaFil: Fornari, M. Cecilia. Universidad de Buenos Aires. Facultad de Medicina. Cátedra de Farmacología; ArgentinaFil: Ortega, María Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Diez, Roberto A.. Universidad de Buenos Aires. Facultad de Medicina. Cátedra de Farmacología; ArgentinaFil: Cabrera, Jose Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Perez, Cristina. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Farmacología; Argentin

Alterations in cell adhesion molecules and other biomarkers of cardiovascular disease in patients with metabolic syndrome

Metabolic syndrome is considered a hyperinsulinemic and inflammatory state closely associated to endothelial dysfunction causing an increased incidence of ischemic cardiovascular events and high mortality. The main objective of the present study was to determine whether leukocitary and soluble cell adhesion molecules were altered in patients with metabolic syndrome in comparison with control subjects. Cell adhesion molecules, mainly of leukocitary location, have been not previously evaluated in specifically designed cross-sectional studies involving male patients with metabolic syndrome. Moreover, other circulating markers of different candidate atherogenic risk parameters were also studied and the potential existence of a progressive relation between the number of metabolic syndrome components and the above mentioned biomarkers was analyzed. Thirty one male patients with metabolic syndrome (ATPIII definition) and 56 male control subjects were studied. We evaluated different markers of insulin resistance, inflammation and atherosclerosis, as well as protective factors. Patients with metabolic syndrome showed (a) hypoadiponectinemia (4551 ± 2302 ng/ml vs. 5865 ± 2548 ng/ml, respectively; p < 0.05), (b) an atherogenic lipid and lipoprotein profile, (c) altered HDL chemical composition accompanied by higher cholesteryl ester-triglyceride interchange carried out by CETP, (d) diminished Lp-PLA2 activity (6.5 ± 1.9 vs. 7.3 ± 2.2, p < 0.05, respectively), antioxidant enzyme related with LDL oxidation, which was positively associated with QUICKI and negatively with VCAM-1 and lymphocyte CD18, and (e) high soluble (VCAM-1: 17 ± 5 vs. 13 ± 4 ng/ml, respectively; p < 0.0005) and leukocyte adhesion molecule expression (monocyte CD54: 52 ± 15 vs. 45 ± 12 arbitrary units, respectively; p < 0.0005; and lymphocyte CD49d: 312 ± 56 vs. 284 ± 64 arbitrary units, respectively; p < 0.05). The increment in leukocyte and soluble cell adhesion molecules, crucial for leukocyte interaction with the endothelium and migration into the artery wall, in combination with the other disorders described above reinforce the presence of a clinical status with high propensity to type 2 diabetes and atherosclerotic cardiovascular disease.Fil: Gomez Rosso, Leonardo Adrián. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Benítez, María Belén. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; ArgentinaFil: Fornari, María Cecilia. No especifíca;Fil: Berardi, Vanina. No especifíca;Fil: Lynch, Santiago. Universidad Favaloro; ArgentinaFil: Schreier, Laura Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; ArgentinaFil: Wikinski, Regina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; ArgentinaFil: Cuniberti, Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad Favaloro; ArgentinaFil: Brites, Fernando Daniel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin