Social environment improves immune function and redox state in several organs from prematurely aging female mice and increases their lifespan.

Aging is associated with a chronic oxidative stress (increase of oxidants and decrease of antioxidants), which contributes to immunosenescence and therefore shorter longevity. Nevertheless, a positive social network has been related to the adequate maintenance of health and deceleration of aging. Adult prematurely aging mice (PAM) are characterized by their inadequate stress response to a T-maze, showing premature immunosenescence and oxidative stress establishment. These impairments contribute to shorter life spans in comparison to exceptional non-PAM (ENPAM). However, it is not known whether these characteristics of PAM could be prevented by a positive cohabitation. Therefore, the aim of the present work was to determine if the premature immunosenescence and oxidative stress shown by PAM could be avoided by the cohabitation with ENPAM, increasing their life span. Female CD1 PAM and ENPAM were divided into three experimental groups: PAM controls, ENPAM controls and a social environment experimental group, containing in the same cage ENPAM and PAM (proportion 5/2, respectively). After 2 months, mice were sacrificed and spleen, thymus, liver and heart removed. Later, several immune functions as well as oxidative stress parameters were assessed in spleen and thymus leukocytes. Also, several oxidative stress parameters were analyzed in liver and heart. The results showed that PAM, after co-housing with ENPAM, had improved immune functions and redox balance in spleen and thymus leukocytes. This improvement of redox state was also observed in liver and heart. Furthermore, all these positive effects seem to be related to the increased life span of PAM.

Papel de las microvesículas como biomarcadores y futuras dianas farmacológicas de enfermedades cardiovasculares / Role of microvesicles as biomarkers and future pharmacology targets of cardiovascular diseases

En la década de los 90 se descubrió un nuevo sistema de comunicación célula-célula a través de vesículas con moléculas bioactivas liberadas al espacio extracelular. Estas vesículas, conocidas como vesículas extracelulares (VE), actúan como reguladores de procesos fisiológicos, pero también participan en el desarrollo y progresión de múltiples patologías. Las microvesículas (MVs) son un tipo de VE que se producen como resultado del daño celular, y están implicadas en la etiopatogenia de un gran número de enfermedades cardiovasculares porque intervienen en el inicio de la aterosclerosis. Diferentes fármacos cardioprotectores han demostrado tener un efecto sobre las MVs; por otro lado, desde que se conoce su capacidad para transferir información biológica, el uso de las éstas como vehículos de suministro molecular ha adquirido interés científico. El objetivo de este trabajo es analizar la implicación de las MVs en la etiopatogenia de la aterosclerosis estableciendo su importancia como biomarcadores de diagnóstico y de seguimiento. Se revisará el efecto farmacológico de las terapias actuales sobre las MVs y se discutirá su papel como herramienta terapéutica

In the 1990's, it was discovered a new cell-cell communication system based on the action of vesicles that cargo bioactive molecules, on neighboring cells. These vesicles, known as extracellular vesicles (EVs) act as regulators of several physiological processes but also participate in the development and progression of multiple diseases. Microvesicles (MVs) are types of EVs that are implicated in the etiopathogenesis of a large number of cardiovascular diseases due to they take part in the onset of atherosclerosis. Different cardioprotective drugs have shown to have an effect on MVs. In addition, since the discovery that MVs are capable of transferring biological information, the use of them as drug delivery vehicles has gained scientific interest. The aim of this work is to analyze the involvement of MVs in the origin of atherosclerosis to demonstrate their role as diagnostic biomarkers, as well as to review the pharmacological effect of current therapies on MVs and their role as therapeutic tool

Age-related changes in xanthine oxidase activity and lipid peroxidation, as well as in the correlation between both parameters, in plasma and several organs from female mice

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Xanthine oxidase, a purine catabolism enzyme, has been implicated as an important source of oxidant production and plays an essential role in several inflammatory and oxidative stress-related diseases. It is known that the increasing levels of oxidants cause the chronic oxidative stress characteristic of the ageing process. The aim of the present work was to determine the changes in xanthine oxidase activity and oxidative damage to lipids in several organs (liver, kidney, spleen, lung and two different brain areas, namely cerebral cortex and brainstem) and plasma from two different age groups of BALB/c female mice: adult (7-month-old) and old (18-month-old) mice, as well as to analyse the possible correlation between both parameters. Xanthine oxidase activity was significantly increased in liver, cerebral cortex and plasma from old mice in comparison with adults. Similar results were obtained in the lipid peroxidation levels, in which old mice showed a high increment in liver and cerebral cortex. Moreover, the results show a significant and positive correlation between xanthine oxidase activity and lipid peroxidation levels in cerebral cortex. The age-related increase in the xanthine oxidase activity and lipid peroxidation in liver and cerebral cortex of mice seems to suggest that the xanthine oxidase plays a role in the acceleration of the oxidative damage in these organs with age and its possible contribution to the pathophysiological changes associated to the process of ageing (AU)

The aged-related increase in xanthine oxidase expression and activity in several tissues from mice is not shown in long-lived animals.

Xanthine oxidase (XO) is an important source of oxidant production and plays an essential role in several oxidative stress-related diseases. Aging is associated with a progressive deregulation of homeostasis as a result of a chronic oxidative stress situation. In the present work the age-related changes in XO expression and activity, as well as the activities of superoxide dismutase and catalase have been investigated in liver, kidney and thymus from four different age groups of mice, including long-lived animals. Furthermore, we have evaluated the contribution of the XO to the oxidative stress-associated with aging, in comparison to another enzymatic key source of oxidant generation, the NADPH oxidase, in peritoneal leukocytes from old mice. In all the tissues analyzed, the old mice showed higher activity and expression of XO, and decreased or unchanged superoxide dismutase and catalase activities as compared with adult mice. Moreover, the inhibition of reactive oxygen species with allopurinol or apocynin in peritoneal leukocytes from old mice, suggest that both XO and NADPH oxidase contribute to the generation of superoxide anion, whereas the XO may have a special relevance in the production of hydrogen peroxyde. Finally, long-lived animals showed a well-preserved redox state, in terms of antioxidant defenses and oxidant compounds in tissues and immune cells, which may be related to the ability of these subjects to reach a very advanced age in healthy condition. These results confirm that XO plays an important role in the age-related oxidative stress in tissues and immune cells.

Age-related changes in xanthine oxidase activity and lipid peroxidation, as well as in the correlation between both parameters, in plasma and several organs from female mice.

Xanthine oxidase, a purine catabolism enzyme, has been implicated as an important source of oxidant production and plays an essential role in several inflammatory and oxidative stress-related diseases. It is known that the increasing levels of oxidants cause the chronic oxidative stress characteristic of the ageing process. The aim of the present work was to determine the changes in xanthine oxidase activity and oxidative damage to lipids in several organs (liver, kidney, spleen, lung and two different brain areas, namely cerebral cortex and brainstem) and plasma from two different age groups of BALB/c female mice: adult (7-month-old) and old (18-month-old) mice, as well as to analyse the possible correlation between both parameters. Xanthine oxidase activity was significantly increased in liver, cerebral cortex and plasma from old mice in comparison with adults. Similar results were obtained in the lipid peroxidation levels, in which old mice showed a high increment in liver and cerebral cortex. Moreover, the results show a significant and positive correlation between xanthine oxidase activity and lipid peroxidation levels in cerebral cortex. The age-related increase in the xanthine oxidase activity and lipid peroxidation in liver and cerebral cortex of mice seems to suggest that the xanthine oxidase plays a role in the acceleration of the oxidative damage in these organs with age and its possible contribution to the pathophysiological changes associated to the process of ageing.

Gestational and lactational lead intoxication produces alterations in the hepatic system of rat pups.

The effects of lead (Pb) intoxication during pregnancy and lactation were studied in the hepatic system of pups and young Wistar rats to test the hypothesis that gestational and lactational lead exposure alters the normal function of the liver in neonates. Lead acetate (300 mg/L) dissolved in distilled water was administered ad libitum to mothers during gestation and lactation. At days 12 and 21 postnatal (PN), pups were sacrificed, blood was collected, and livers were removed. Blood lead (PbB) levels were also measured. Although, histological evaluation revealed neither abnormalities in the liver structure nor depositions of lead, the toxicant produced biochemical alterations. Lead-intoxicated pups exhibited a decrease in hemoglobin, iron, and alkaline and acid phosphatase levels and an increase in PbB content. Protein, DNA, and lipid total amounts were reduced, and hepatic glycogen content was diminished at days 12 and 21 PN, with a higher level of glucose in the blood. Lead administration also resulted in a decrease in alkaline phosphatase in the liver of pups at day 21 PN, but acid phosphatase was unaltered. The findings of this study support the hypothesis that lead intoxication of mothers in gestation and lactation results in alterations in the hepatic system in neonates and pups.

Lead intoxication in gestational and lactation periods alters the development of male reproductive organs.

The effect of lead (Pb) intoxication during pregnancy and lactation on the male reproductive system was studied to evaluate the alterations caused by Pb in the development of pups. The investigations covered the effect of lead on the course of spermatogenesis and the development of the epididymis and reproductive glands. For this purpose, dams were intoxicated with 300 mg/L Pb during the gestational period and through lactation. Pups were sacrificed on Postnatal (PN) Days 12 and 21. Blood lead (PbB) and plasma iron concentrations were measured, and blood cells counted. Biochemical studies as well as histochemical analyses were performed on testes and accessory glands of the reproductive system. Lead intoxication resulted in a decrease in testis and seminal vesicle weights and an increase in DNA and RNA levels on PN Day 21. Total protein was significantly decreased by the toxicant, and alkaline and acid phosphatase levels of the gonads were reduced. Effects were also reflected in the reduction of the thickness of epithelium and of seminiferous tubule diameter (STD) as a consequence of the action of lead in the reduction in numbers of prospermatogonia and spermatocytes. Results indicate that the reproductive system targets of lead intoxication are not only the testes; lead intoxication results in the inhibition of testicular, epididymal, and seminal vesicle function, altering the biochemical composition of these organs, and consequently, affecting the normal development of germinal cells.