Antisclerothic effect of tibolone by reducing proinflammatory cytokines expression, ROS production and LDL-ox uptake in THP-1 macrophages.

BACKGROUND: Cardiovascular disease is more frequent in menopausal women, which has been related to factor such as weight gain, altered fat distribution, and increased inflammation markers including adipokines (MCP-1, TNF-α, IL-6) and cytokines (IL-1, IL-6, TNF-α) produced by macrophages. In addition to their phagocytic activity, macrophages secrete cytokines and chemokines that induces cell recruitment, which is a process related to vascular damage that favors the formation of atheromatous plaques. Tibolone (Tb) therapy is used to reduce the symptoms of menopause as well as osteoporosis and it has been shown to decreases the risk of fractures. METHODS: To investigate the effect of tibolone in macrophage enzymatic activity, gene expression of cytokines, and its effect on foam cells formation. We use phorbol-12-myristate-13-acetate (PMA)-differentiated THP-1 cells. The cells were incubated 24 h and 48 h using pre and post-treatment schemes. We evaluated total ROS determination by NBT assay, expression of cytokines (IL-1ß, IL-6, TNF-α, NOS2, ARG1, TGFß) by RT-qPCR and foam cell formation in THP-1 differentiated macrophages stimulated with PMA. RESULTS: It was observed that the minor levels of total ROS determination were obtained with tibolone at 48 h in post-treatment scheme. Also, in a long term we found decrease the proinflammatory cytokines (IL-1ß, IL-6 and TNF-α). Finally, with treatment for 24 h with P4 y Tb we observed fewer LDL vesicles into macrophages cytoplasm. CONCLUSIONS: These results suggest that tibolone reduces the inflammatory process, also inhibits the foam cells formation; suggesting a possible role in reducing cardiovascular risk.

Analysis of Antioxidant Consumption, Body Mass Index and the Waist-Hip Ratio in Early Postmenopause.

Oxidative stress is present in early postmenopause. Antioxidants, present in food, avoid or limit the damage caused by free radicals. The aim of this study was to analyze whether the consumption of vitamin A, vitamin C, and Selenium was adequate in postmenopausal women and its relationship with levels of malondialdehyde. A descriptive, cross-sectional prospective clinical study was carried out with 132 women (45⁻55 years old) in postmenopause. The body mass index (BMI) and the waist-to-hip ratio (WHR) were calculated. The participants were surveyed about their food consumption for seven days. The plasmatic concentration of malondialdehyde was quantified by the methyl-phenyl-indole method. The women were grouped according to their BMI. All groups showed similar consumption of proteins, lipids, and carbohydrates, which exceeded the daily recommended level. According to the WHR, 87% had android fat distribution. Selenium, vitamin C, and vitamin A intake were below the daily recommended/suggested levels. The greater the BMI, the higher the plasmatic concentration of malondialdehyde in the patients. It was observed an elevated caloric intake, android fat distribution, and a greater BMI was accompanied by a lower consumption of antioxidants and an increased level of malondialdehyde.

Vertical sleeve gastrectomy improves indices of metabolic disease in rodent model of surgical menopause.

OBJECTIVE: Although women are the most common recipients of weight loss surgeries for the amelioration of the comorbidities of obesity, few studies have addressed the efficacy of these procedures with specific attention to reproductive stage. Here we ask in a rodent model of vertical sleeve gastrectomy (VSG) whether improvements to metabolic health are realized in women having received surgical menopause. Specifically we were interested in knowing whether rats made menopausal through surgical means would exhibit persistent hepatic steatosis as reported in previously pregnant, freely cycling female VSG rats or if it is resolved as reported in male VSG rats. METHODS: All the rats first received ovariectomy (OVX) and then were placed on high-fat diet before either sham or VSG surgery (N = 12, 9) and then were monitored for resolution of obesity-related comorbidities. RESULTS: VSG was sufficient to reduce weight and adiposity in OVX females in comparison to obese rats (P < 0.001). Glucose tolerance (P < 0.05) was improved in OVX-VSG females with no change in insulin sensitivity. Both circulating (P < 0.01) and hepatic triglyceride (P < 0.01) levels were also reduced after VSG. Liver integrity was improved in OVX-VSG in comparison to OVX-obese as reflected by reduced aspartate aminotransferase levels (P < 0.05). The ability of mitochondria to generate adenosine triphosphate was maintained, and an increase in complex IV may decrease the production of mitochondrial reactive oxygen species. CONCLUSIONS: Taken together, VSG in OVX rats experience many positive benefits including the resolution of hepatic steatosis that persists in reproductively intact female rats after VSG.