Behavior of Oxidative Stress Markers in Alcoholic Liver Cirrhosis Patients.

Alcohol is the most socially accepted addictive substance worldwide, and its metabolism is related with oxidative stress generation. The aim of this work was to evaluate the role of oxidative stress in alcoholic liver cirrhosis (ALC). This study included 187 patients divided into two groups: ALC, classified according to Child-Pugh score, and a control group. We determined the levels of reduced and oxidized glutathione (GSH and GSSG) and the GSH/GSSG ratio by an enzymatic method in blood. Also, protein carbonyl and malondialdehyde (MDA) content were estimated in serum. MDA levels increased in proportion to the severity of damage, whereas the GSH and GSSG levels decreased and increased, respectively, at different stages of cirrhosis. There were no differences in the GSH/GSSG ratio and carbonylated protein content between groups. We also evaluated whether the active consumption of or abstinence from alcoholic beverages affected the behavior of these oxidative markers and only found differences in the MDA, GSH, and GSSG determination and the GSH/GSSG ratio. Our results suggest that alcoholic cirrhotic subjects have an increase in oxidative stress in the early stages of disease severity and that abstinence from alcohol consumption favors the major antioxidant endogen: GSH in patients with advanced disease severity.

Human monocytes and macrophages undergo M1-type inflammatory polarization in response to high levels of glucose.

Emerging data suggest that elevated glucose may promote inflammatory activation of monocytic lineage cells with the ability to injure vascular endothelial tissue of diabetic patients, however evidence in primary human monocytes and macrophages is still insufficient. We investigated the effect of high glucose concentration on the inflammatory capacity of human macrophages in vitro and examined whether similar responses were detectable in circulating monocytes from prediabetic patients. Primary monocytes were isolated from healthy blood donors and differentiated into macrophages. Differentiated macrophages were exposed to normal levels of glucose (NG), high glucose (HG) or high mannitol as osmotic pressure control (OP) for three days. Using PCR, ELISA and flow cytometry, we found that HG macrophages showed overexpression of CD11c and inducible nitric oxide synthase as well as down-regulation of arginase-1 and interleukin (IL)-10 with respect to NG and OP macrophages. Consistent with in vitro results, circulating monocytes from hyperglycemic patients exhibited higher levels of CD11c and lower expression of CD206 than monocytes from normoglycemic controls. In subjects with hyperglycemia, elevation in CD11c(+) monocytes was associated with increased obesity, insulin resistance, and triglyceridemia as well as low serum IL-10. Our data suggest that human monocytes and macrophages undergo M1-like inflammatory polarization when exposed to high levels of glucose on in vitro culture conditions and in patients with hyperglycemia. These results demonstrate that excess glucose has direct effects on macrophage activation though the molecular mechanisms mediating such a response remain to be elucidated.

Hyperleptinemia is associated with parameters of low-grade systemic inflammation and metabolic dysfunction in obese human beings.

Leptin is an adipose tissue-derived hormone that has been involved in hypothalamic and systemic inflammation, altered food-intake patterns, and metabolic dysfunction in obese mice. However, it remains unclear whether leptin has a relationship with parameters of systemic inflammation and metabolic dysfunction in humans. We thus evaluated in a cross-sectional study the circulating levels of leptin in 40 non-obese and 41 obese Mexican individuals, examining their relationship with tumor necrosis factor alpha (TNF-α), interleukin (IL) 12, IL-10, central obesity, serum glucose and insulin levels, and serum triglyceride and cholesterol concentrations. Circulating levels of leptin, TNF-α, IL-12, IL-10, and insulin were measured by ELISA, while concentrations of glucose, triglyceride, and cholesterol were determined by enzymatic assays. As expected, serum levels of leptin exhibited a significant elevation in obese individuals as compared to non-obese subjects, showing a clear association with increased body mass index (r = 0.4173), central obesity (r = 0.4678), and body fat percentage (r = 0.3583). Furthermore, leptin also showed a strong relationship with serum TNF-α (r = 0.6989), IL-12 (r = 0.3093), and IL-10 (r = -0.5691). Interestingly, leptin was also significantly related with high concentrations of fasting glucose (r = 0.5227) and insulin (r = 0.2229), as well as elevated levels of insulin resistance (r = 0.3611) and circulating triglyceride (r = 0.4135). These results suggest that hyperleptinemia is strongly associated with the occurrence of low-grade systemic inflammation and metabolic alteration in obese subjects. Further clinical research is still needed to determine whether hyperleptinemia may be a potential marker for recognizing the advent of obesity-related metabolic disorders in human beings.