The treatment with an anti-glycosaminoglycan antibody reduces aortic oxidative stress in a rabbit model of atherosclerosis.

Retained low-density lipoproteins (LDL) by arterial glycosaminoglycans (GAG) are more susceptible to reactive oxygen species-mediated oxidation, contributing to oxidative stress and atherosclerosis. Recently, we reported the properties of the chimeric mouse/human monoclonal antibody chP3R99-LALA to bind sulfated GAG, to inhibit LDL-chondroitin sulfate binding, and to avoid LDL oxidation in vitro. Here, we hypothesized that chP3R99-LALA treatment might reduce aortic oxidative stress in a therapeutic setting. Redox biomarkers and serum lipids were determined by spectrophotometric methods. Subcutaneous administration of five doses (100 µg) of chP3R99-LALA, after Lipofundin administration (2 mL/kg/day, i.v.) during 8 days, reduced atherosclerotic lesion development, which was not associated with a serum lipid modulation. In contrast, the treatment with chP3R99-LALA reduced (p < 0.05) malondialdehyde and protein oxidation, induced a restoration of reduced glutathione level, of the superoxide dismutase and catalase activities and of endothelial nitric oxide level. Thus, the antiatherogenic effect of chP3R99-LALA treatment seems to be associated with a reduction of aortic oxidative stress. These results contribute in understanding the molecular mechanisms associated with chP3R99-LALA atheroprotection and support the use of anti-GAG antibody-based immunotherapy as a potential tool to treat the atherosclerosis.

Respuesta de ratones Balb/c frente a ciclofosfamida y bleomicina en el ensayo cometa alcalino de linfocitos de sangre periférica / Balb/c mice response against cyclophosphamide and bleomycin in the alkaline comet assay of peripheral blood lymphocytes

En este artículo se evaluó el efecto mutágenico de la ciclofosfamida y bleomicina, con el objetivo de armonizar el número de exposiciones al ser utilizadas como controles positivos en ensayos in vivo de genotoxicidad, mediante el ensayo cometa alcalino. Se realizó en linfocitos de sangre periférica, utilizando 10 ratones/grupo/sexo de la línea Balb/c como biomodelo experimental. Fueron formados 5 grupos experimentales/sexo, el primero administrado con NaCl al 0,9% por vía intraperitoneal (i.p) como control negativo. El segundo y el tercero administrados con ciclofosfamida por vía i.p, con diseños de tratamientos diferentes en dosis de 50 mg/kg. El cuarto y quinto grupo fueron administrados con bleomicina por vía i.p, igualmente en dos diseños de tratamientos diferentes en dosis de 20 mg/kg. El mayor valor de inducción de daño se obtuvo con el uso de la ciclofosfamida y bleomicina, ambas en el diseño de administración de 48 y 24 horas antes de la eutanasia. Este estudio será aplicable a la evaluación de drogas que no han sido exploradas en el ámbito de la antigenotoxicidad y genotoxicidad in vivo. Además permitirá contar con un mayor conocimiento acerca de este ensayo, favoreciendo su validación (AU)

In this article were evaluated the mutagenic effect of cyclophosphamide and bleomycin, with the objective of harmonizing the number of exhibitions when being used as positive controls on in vivo genotoxicity assay, by means of alkaline comet assay. It was carried out in peripheral blood lymphocytes, using 10 mice/group/sex of the Balb/c line as experimental biomodel. We were formed 5 experimental groups per sex. The first group was administered with NaCl 0,9 % by intraperitoneal (i.p) route. The second and third groups were administered with cyclophosphamide by i.p route, with designs of different treatments at doses of 50 mg/kg. The fourth and fifth groups were administered with bleomycin by i.p route, equally in two designs of different treatments at doses of 20 mg/kg. The bigger inductions of damage were obtained with the use of the cyclophosphamide and bleomycin, both in the design of 48 and 24 hours administration before the euthanasia. This study will be applicable to the drugs evaluation that they have not been explored in to the in vivo antigenotoxicity and genotoxicity environment. It will also allow having a bigger knowledge about this assay, favoring their validation (AU)

Comparación de la respuesta de ratas Sprague Dawley frente a ciclofosfamida y bleomicina en el ensayo de la morfología de la cabeza del espermatozoide / Comparison of the Sprague Dawley rat’s response against cyclophosphamide and bleomycin in the head sperm morphology assay

El ensayo de la morfología de la cabeza del espermatozoide permite el estudio del potencialgenotóxico de muestras problemas a nivel celular, esta herramienta evalúa los cambios efectuados enla concentración espermática, así como el aumento de la frecuencia espontánea de cabezas deespermatozoides morfológicamente anormales. En este artículo decidimos evaluar y comparar en elbiomodelo de ratas Sprague Dawley machos, el efecto de dos sustancias mutagénicas en este ensayo,la Ciclofosfamida (CF) en dosis de 50 mg/kg y la Bleomicina (BL) en dosis de 30 mg/kg,administradas por vía intraperitoneal durante 5 días consecutivos, siendo sacrificados los animales 52días después de la última administración de los mutágenos. Se obtuvo como resultado que ambosmutágenos disminuyeron la concentración espermática y aumentaron el índice espontáneo de cabezasanómalas en los espermatozoides, siendo observado un marcado efecto mutagénico en la CF encomparación con la BL. Al final de la experiencia se obtuvieron mayores resultados de inducción decabezas de espermatozoides anómalas con el uso de la CF. Estos resultados reafirman el uso de estemutágeno como control positivo eficiente y seguro en este ensayo el cual se encuentra incluido en losestudios de genotoxicidad y toxicología de la fertilidad(AU)

The head sperm morphology assay, allows the study of the genotoxic potencial of samples at thecellular level problems; this tool to evaluate the spermatic concentration changes, as well as theincrease of the spontaneous heads frequency of sperms morphology abnormal. In this article we decideto evaluate and to compare in the Sprague Dawley males rats, the effect of two mutagenic substancesin these assay, the Cyclophosphamide, (CF) in dose of 50 mg/kg and the Bleomycin (BL) in dose of30 mg/kg, administered by intraperitoneal route during 5 consecutive days, being sacrificed theanimals 52 days after the last administration of the mutagens. It was obtained that both mutagendiminished the spermatic concentration and they increased the spontaneous index of anomaloussperms heads, being observed a marked mutagenic effect in the CF in comparison with the BL. At theend of the experience bigger results of induction of anomalous heads sperms were obtained with theuse of the CF. These results reaffirm the use of this mutagen as efficient and safe positive control inthis assay which is included in the genotoxicity studies and fertility toxicology(AU)

Comparison of the effect of the hipocolesteromiante treatment of the atorvastatin, with the combination atorvastatina-policosanol as well as the possible action on the state oxiation - redution, in patient with vascular affections in lower limbs

It has been shown that a decrease in the concentrations of total cholesterol and LDL-col by diets and drugs reduces the peripheral vascular disease risk. Policosanol and Atorvastatin have shown they are capable of reducing both parameters in type II hypercholesterolemia. Some of the steps in the mechanism of action of these drugs are different and could show results sums, when we used in combination. They also show a pleiotropic effect given by its general antioxidant action on lipid peroxidation. OBJECTIVES. To compare the effect of treatment with the combination with Atorvastatin and Atorvastatin - Policosanol n cholesterol concentrations of atherogenic lipoproteins, and the possible antioxidant action. PATIENTS AND METHODS. We studied 104 patients of both sexes in a range of ages between 40 and 60 years. It was taken as a criterion for inclusion Col-LDL levels above 3.3 mmol/L. Patients were randomly distributed into two groups (one treated with Atorvastatin and the other with Atorvastatin + Policosanol). Measurements were made of serum lipoproteins, and hemodynamic studies and oxidative stress before and after three months of treatment. RESULTS. Was found when comparing the groups among themselves, a decrease (p <0.05) in the values of T Col, Col-LDL, TG, VLDL and RAC. Average values were lower (p <0.05) from Col-LDL in the group treated with the combination of both drugs, as well as variations in the parameters which measure oxidative stress ( GSH (p <0.05) increased and MDA decreased). CONCLUSION. The combination of Policosanol and Atorvastatin in the treatment of hypercholesterolemic patients offers better results than using each separately (AU)

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