Effect of DHEA and metformin on corpus luteum in mice

Effect of DHEA and metformin on corpus luteum in mice Abstract We evaluated the effect of hyperandrogenism in ovaries with functional and regressing corpora lutea (CL) and the action of metformin in preventing these possible alterations using a mouse model. To obtain a CL functional for 9+/-1 days, immature female mice of the BALB/c strain were injected i.p. with 10 IU/mouse of pregnant mare´s serum gonadotropin (PMSG). DHEA (60 mg/kg body weight s.c., 24 and 48 h prior to kill) decreased both serum progesterone (P) and estradiol (E(2)) levels and increased the activity of superoxide dismutase (SOD) from ovaries with functional CL (on day 5 after PMSG). It increased P and E(2) and the activities of SOD and catalase (CAT) and decreased lipoperoxidation of ovaries with regressing CL (on day 9 after PMSG). Treatment with DHEA did not affect the production of prostaglandin F(2alpha) (PGF(2alpha)) or PGE by ovaries with functional CL, whereas DHEA decreased PGF(2alpha) and increased PGE production by ovaries with regressing CL. Metformin (50 mg/kg body weight, orally) given together with DHEA restored E(2) levels from mice with ovaries with functional CL and serum P, PGF(2alpha) and PGE levels, and oxidative balance in mice with ovaries with regressing CL. Metformin alone was able to modulate serum P and E(2) levels, lipoperoxidation, SOD and CAT, and the 5,5-dimethyl-1-pyrroline N-oxide/(*)OH signal. These findings suggest that hyperandrogenism is able to induce or to rescue CL from luteolysis and metformin treatment is able to prevent these effects.Fil: Sander, Valeria Analía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas (subsede Chascomús) | Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas (subsede Chascomús); ArgentinaFil: Facorro, Graciela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Físico Matemática; ArgentinaFil: Piehl, Lidia Leonor. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Físico Matemática; ArgentinaFil: Rubin de Cellis, E. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Fisicomatemática. Cátedra de Física; ArgentinaFil: Motta, Alicia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentin

Effects of photooxidation on membrane integrity in Salix nigra seeds

Background and Aims: Salix nigra seeds are desiccation-tolerant, as are orthodox seeds, although in contrast to other orthodox seeds they lose viability in a few weeks at room temperature. They also differ in that the chloroplasts of the embryo tissues conserve their chlorophyll and endomembranes. The aim of this paper was to investigate the role of chlorophyll in seed deterioration. Methods: Seeds were aged at different light intensities and atmospheric conditions. Mean germination time and normal and total germination were evaluated. The formation of free radicals was assessed using electronic spin resonance spectroscopy, and changes in the fatty acid composition from phospholipids, galactolipids and triglycerides using gas-liquid chromatography. Membrane integrity was studied with electronic spin resonance spin probe techniques, electrolyte leakage and transmission electron microscopy. Key Results: Light and oxygen played an important role in free-radical generation, causing a decrease in normal germination and an increase in mean germination time. Both indices were associated with a decrease in polyunsaturated fatty acids derived from membrane lipids as phospholipids and galactolipids. The detection of damage in thylakoid membranes and an increase in plasmalemma permeability were consistent with the decrease in both types of lipids. Triglycerides remained unchanged. Light-induced damage began in outermost tissues and spread inwards, decreasing normal germination. Conclusions: Salix nigra seeds were very susceptible to photooxidation. The thylakoid membranes appeared to be the first target of the photooxidative process since there were large decreases in galactolipids and both these lipids and the activated chlorophyll are contiguous in the structure of that membrane. Changes in normal germination and mean germination time could be explained by the deteriorative effects of oxidation.Instituto de Investigaciones Bioquímicas de La Plat

Effects of photooxidation on membrane integrity in Salix nigra seeds

Background and Aims: Salix nigra seeds are desiccation-tolerant, as are orthodox seeds, although in contrast to other orthodox seeds they lose viability in a few weeks at room temperature. They also differ in that the chloroplasts of the embryo tissues conserve their chlorophyll and endomembranes. The aim of this paper was to investigate the role of chlorophyll in seed deterioration. Methods: Seeds were aged at different light intensities and atmospheric conditions. Mean germination time and normal and total germination were evaluated. The formation of free radicals was assessed using electronic spin resonance spectroscopy, and changes in the fatty acid composition from phospholipids, galactolipids and triglycerides using gas-liquid chromatography. Membrane integrity was studied with electronic spin resonance spin probe techniques, electrolyte leakage and transmission electron microscopy. Key Results: Light and oxygen played an important role in free-radical generation, causing a decrease in normal germination and an increase in mean germination time. Both indices were associated with a decrease in polyunsaturated fatty acids derived from membrane lipids as phospholipids and galactolipids. The detection of damage in thylakoid membranes and an increase in plasmalemma permeability were consistent with the decrease in both types of lipids. Triglycerides remained unchanged. Light-induced damage began in outermost tissues and spread inwards, decreasing normal germination. Conclusions: Salix nigra seeds were very susceptible to photooxidation. The thylakoid membranes appeared to be the first target of the photooxidative process since there were large decreases in galactolipids and both these lipids and the activated chlorophyll are contiguous in the structure of that membrane. Changes in normal germination and mean germination time could be explained by the deteriorative effects of oxidation.Instituto de Investigaciones Bioquímicas de La Plat

Synergistic encapsulation of the anti-HIV agent efavirenz within mixed poloxamine/poloxamer polymeric micelles

This study investigated the synergistic performance of mixed polymeric micelles made of linear and branched poly(ethylene oxide)-poly(propylene oxide) for the more effective encapsulation of the anti-HIV drug efavirenz. The co-micellization process of 10% binary systems combining different weight ratios of a highly hydrophilic poloxamer (Pluronic F127) and a more hydrophobic poloxamine counterpart (Tetronic T304 and T904) was investigated by means of dynamic light scattering, cloud point and electronic spin resonance experiments. Then, the synergistic solubilization capacity of the micelles was shown. Findings revealed a sharp solubility increase from 4 μg/ml up to more than 33 mg/ml, representing a 8430-fold increase. Moreover, the drug-loaded mixed micelles displayed increased physical stability over time in comparison with pure poloxamine ones. Overall findings confirmed the enormous versatility of the poloxamer/poloxamine systems as Trojan nanocarriers for drug encapsulation and release by the oral route and they entail a relevant enhancement of the previous art towards a more compliant pediatric HIV pharmacotherapy. From the Clinical Editor: In this study, the authors demonstrate the versatility of poloxamer/poloxamine systems as Trojan nanocarriers for anti-HIV drug encapsulation and release by the oral route. A highly relevant stability and solubility enhancement is shown, which may ultimately lead to more compliant anti-HIV pharmacotherapy.Fil: Chiappetta, Diego Andrés. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria; ArgentinaFil: Facorro, Graciela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Físico Matemática; ArgentinaFil: Rubín de Celis, Emilio. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Físico Matemática; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sosnik, Alejandro Dario. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria; Argentin

New technique to quantify phospolipids in disordered phase in lung surfactant by electron spin resonance

In pulmonary surfactant (PS) the coexistence of the ordered (Lo) and disordered (Ld) lipid phases would be essential for an optimal activity. Electron spin resonance (ESR) of PS labeled with 5-doxil stearic acid shows two spectral components called S and W. S/W ratio could be understood as the ratio between the probe population in Lo and in Ld. Although the specificity of S/W as an indicator of Lo/Ld has not yet been demonstrated, S/W has been used qualitatively to study changes in Lo/Ld. The goal of this paper is to stablish the correlation between S/W parameter and the amount of lipids in Ld (%Ld) measured by the ESR TEMPO technique described in our previous work. S/W and %Ld were measured in different PS samples under different experimental conditions. The results showed an inverse correlation between S/W and %Ld (r = −0.983; p < 0.001). We demonstrated that the S/W is sensible to the changes of Lo/Ld and can be used to quantify the %Ld.Fil: Cimato, Alejandra Noemi. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Fisicomatemática. Cátedra de Física; ArgentinaFil: Facorro, Graciela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Fisicomatemática. Cátedra de Física; ArgentinaFil: Repetto, Marisa Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analítica y Fisicoquímica. Cátedra de Química General e Inorgánica; ArgentinaFil: Martínez Sarrasague, María Margarita. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Fisicomatemática. Cátedra de Física; Argentin

Effect of serum lipoproteins and cholesterol on an exogenous pulmonary surfactant: ESR analysis of structural changes and their relation with surfactant activity

The study of structural changes in the surfactant may help to understand the mechanisms by which the surfactant is inactivated by serum. Here, we compared the in vitro effects of serum, albumin, lipoproteins (VLDL, LDL, HDL) and cholesterol on the dynamic and structural properties of surfactant suspensions by electronic spin resonance and surface tension measurements. Our results showed that albumin seems to be responsible for macrostructure disaggregation and increased rigidity in the hydrophobic region, but it did not affect surfactant activity. Fluidity in the polar area seems to be critical for proper physiological activity, and the changes induced by serum observed in this area would be generated by HDL or cholesterol, but the amount of cholesterol transferred by serum is not significant. Statistical analysis showed that surfactant activity correlated with the fluidity in the polar area but not with that in the hydrophobic region. We obtained strong evidence that among all the serum components tested, HDL is the one that causes the structural changes that compromise surfactant performance.Fil: Martínez Sarrasague, María Margarita. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Fisicomatemática. Cátedra de Física; ArgentinaFil: Cimato, Alejandra Noemí. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Fisicomatemática. Cátedra de Física; ArgentinaFil: Piehl, Lidia Leonor. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Fisicomatemática. Cátedra de Física; ArgentinaFil: Brites, Fernando Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; ArgentinaFil: Facorro, Graciela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Fisicomatemática. Cátedra de Física; Argentin

Effects of photooxidation on membrane integrity in Salix nigra seeds

Background and Aims: Salix nigra seeds are desiccation-tolerant, as are orthodox seeds, although in contrast to other orthodox seeds they lose viability in a few weeks at room temperature. They also differ in that the chloroplasts of the embryo tissues conserve their chlorophyll and endomembranes. The aim of this paper was to investigate the role of chlorophyll in seed deterioration. Methods: Seeds were aged at different light intensities and atmospheric conditions. Mean germination time and normal and total germination were evaluated. The formation of free radicals was assessed using electronic spin resonance spectroscopy, and changes in the fatty acid composition from phospholipids, galactolipids and triglycerides using gas-liquid chromatography. Membrane integrity was studied with electronic spin resonance spin probe techniques, electrolyte leakage and transmission electron microscopy. Key Results: Light and oxygen played an important role in free-radical generation, causing a decrease in normal germination and an increase in mean germination time. Both indices were associated with a decrease in polyunsaturated fatty acids derived from membrane lipids as phospholipids and galactolipids. The detection of damage in thylakoid membranes and an increase in plasmalemma permeability were consistent with the decrease in both types of lipids. Triglycerides remained unchanged. Light-induced damage began in outermost tissues and spread inwards, decreasing normal germination. Conclusions: Salix nigra seeds were very susceptible to photooxidation. The thylakoid membranes appeared to be the first target of the photooxidative process since there were large decreases in galactolipids and both these lipids and the activated chlorophyll are contiguous in the structure of that membrane. Changes in normal germination and mean germination time could be explained by the deteriorative effects of oxidation.Fil: Roqueiro, Gonzalo. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación de Recursos Naturales. Instituto de Recursos Biológicos; ArgentinaFil: Facorro, Graciela B.. Universidad Nacional de la Plata. Facultad de Ingeniería. Departamento de Fisicomatemática; ArgentinaFil: Huarte, Mónica G.. Universidad Nacional de la Plata. Facultad de Ingeniería. Departamento de Fisicomatemática; ArgentinaFil: Rubín de Celis, Emilio. Universidad Nacional de la Plata. Facultad de Ingeniería. Departamento de Fisicomatemática; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Garcia, Carlos Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Maldonado, Sara Beatriz. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación de Recursos Naturales. Instituto de Recursos Biológicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Maroder, Horacio. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación de Recursos Naturales. Instituto de Recursos Biológicos; Argentina. Universidad Nacional de Luján. Departamento de Ciencias Básicas; Argentin

Structure-anti-leukemic activity relationship study of ortho- dihydroxycoumarins in U-937 cells: Key role of the δ-lactone ring in determining differentiation-inducing potency and selective pro-apoptotic action

Previous studies indicated the need of at least one phenolic hydroxyl group in the coumarin core for induction of cytotoxicity in different cell lines. Herein, we present an exhaustive structure-activity relationship study including ortho-dihydroxycoumarins (o-DHC) derivatives, cinnamic acid derivatives (as open-chain coumarin analogues) and 1,2-pyrones (representative of the δ-lactone ring of the coumarin core), carried out to further identify the structural features of o-DHC required to induce leukemic cell differentiation and apoptosis in U-937 cells. Our results show for the first time that the δ-lactone ring positively influences the aforementioned biological effects, by conferring greater potency to compounds with an intact coumarin nucleus. Most tellingly, we reveal herein the crucial role of this molecular portion in determining the selective toxicity that o-DHC show for leukemic cells over normal blood cells. From a pharmacological perspective, our findings point out that o-DHC may be useful prototypes for the development of novel chemotherapeutic agents.Fil: Vazquez, Ramiro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; ArgentinaFil: Riveiro, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Vermeulen, Elba Monica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Alonso, Eliana. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; ArgentinaFil: Mondillo, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Facorro, Graciela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Fisicomatemática. Cátedra de Física; ArgentinaFil: Piehl, Lidia Leonor. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Fisicomatemática. Cátedra de Física; ArgentinaFil: Gomez, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; ArgentinaFil: Moglioni, Albertina Gladys. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; ArgentinaFil: Fernandez, Natalia Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; ArgentinaFil: Baldi, Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Shayo, Carina Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Davio, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentin