Pro-Resolving Lipid Mediator Resolvin E1 Mitigates the Progress of Diethylnitrosamine-Induced Liver Fibrosis in Sprague-Dawley Rats by Attenuating Fibrogenesis and Restricting Proliferation.

Liver fibrosis is a complex process associated to most types of chronic liver disease, which is characterized by a disturbance of hepatic tissue architecture and the excessive accumulation of extracellular matrix. Resolvin E1 (RvE1) is a representative member of the eicosapentaenoic omega-3 lipid derivatives, and is a drug candidate of the growing family of endogenous resolvins. Considering the aforementioned, the main objective of this study was to analyze the hepatoprotective effect of RvE1 in a rat model of liver fibrosis. Male Sprague-Dawley rats received diethylnitrosamine (DEN, 70 mg/mg body weight intraperitoneally (i.p)) as an inductor of liver fibrosis once weekly and RvE1(100 ng/body weight i.p) twice weekly for four weeks. RvE1 suppressed the alterations induced by DEN, normalizing the levels of alanine aminotransferase (ALT), albumin, and lactate dehydrogenase (LDH), and ameliorated DEN injury by decreasing the architecture distortion, inflammatory infiltration, necrotic areas, and microsteatosis. RvE1 also limited DEN-induced proliferation through a decrease in Ki67-positive cells and cyclin D1 protein expression, which is related to an increase of the levels of cleaved caspase-3. Interestingly, we found that RvE1 promotes higher nuclear translocation of nuclear factor κB (NF-κB)p65 than DEN. RvE1 also increased the levels of nuclear the nuclear factor erythroid 2-related factor 2 (Nrf2), but with no antioxidant effect, measured as an increase in glutathione disulfide (GSSG) and a decrease in the ratio of glutathione (GSH)/GSSG. Taken together, these results suggest that RvE1 modulates the fibrogenesis, steatosis, and cell proliferation in a model of DEN induced fibrosis.

Propolis as an Adjuvant in the Healing of Human Diabetic Foot Wounds Receiving Care in the Diagnostic and Treatment Centre from the Regional Hospital of Talca.

OBJECTIVE: Diabetic foot wounds are a relevant diabetes complication and a major health problem. It has been described that propolis has health benefits due to its anti-inflammatory, antioxidant, and support in the healing process. The current study assessed the effect of propolis as an adjuvant in the healing of human diabetic foot ulcers. This was evaluated in a randomized placebo-controlled study of subjects receiving care in the Diagnostic and Treatment Centre from the Regional Hospital of Talca, Chile. RESEARCH DESIGN AND METHODS: Randomized subjects received ambulatory healing treatment for diabetes foot wounds with propolis spray (3%), which was applied to cover the entire wound surface each time it was dressed from week 0 until cicatrization or 8 weeks as a maximum. Two serum samples were taken (day 0 and end of the study) for cytokine and oxidative stress analyses. Also, macro- and microscopy were analyzed in the process of wound healing. RESULTS: The study comprised 31 subjects with type 2 diabetes in treatment for diabetic foot wounds in the Diagnostic and Treatment Centre from the Regional Hospital of Talca. Propolis promotes a reduction of the wound's area by an average of 4 cm2, related to an increase in the connective tissue deposit compared to the control. Also, propolis increased the glutathione (GSH) and GSH/glutathione disulfide (GSSG) ratio (p < 0.02), depleted tumor necrosis factor- (TNF-) α, and increased interleukin- (IL-) 10 levels. Topical propolis did not modify the biochemical parameters in the serum of the studied subjects. CONCLUSIONS: The topical use of propolis turned out to be an interesting therapeutic strategy as an adjuvant in the care of diabetes foot wounds due to its ability to improve and promote healing based on its anti-inflammatory and antioxidant profile. This trial is registered with NCT03649243.

The Role of Propolis in Oxidative Stress and Lipid Metabolism: A Randomized Controlled Trial.

Although there is evidence of the benefits of propolis on human health, the vast majority of studies have been conducted using animal models. The present study includes the chemical characterization and clinical evaluation of the effects of the oral administration of propolis solution on the oxidative status and modulation of lipids in a human population in Talca, Chile. Chemical characterization of propolis, total phenol, flavonoids, and total antioxidant capacity were determined by ORAC. Identification of phenols and flavonoids in propolis was assessed by HPLC-DAD. A double-blind, placebo-controlled clinical trial was conducted. Subjects provided informed consent form and the Bioethics Committee of the Universidad de Talca approved protocol. Eligible subjects (n = 67) were randomized in two groups: propolis (n = 35) and placebo (n = 32). All subjects were evaluated at 0 (baseline), 45, and 90 days. In the propolis group, we observed that increases in HDL-c went from 53.9 ± 11.9 to 65.8 ± 16.7 mg/dL (p < 0.001) from baseline to 90 days. Compared to placebo subjects, consumption of propolis induced a net increase in GSH levels (p < 0.0001) and a decrease (p < 0.001) in TBARS levels for the propolis group. Our findings indicate potential benefits of propolis use in human health. The use of propolis appears to have positive effects on oxidative status and improvement of HDL-c, both of which contribute to a reduced risk of cardiovascular disease.

High levels of iron status and oxidative stress in patients with metabolic syndrome.

Studies concerning oxidative stress (OxE) parameters have increased, mainly because of its important role in cardiovascular diseases and diabetes complications. The main objective of this study was to evaluate iron nutrition status and oxidative stress parameters in subjects that had developed metabolic syndrome (MetS). Subjects from the Research Program of Risk Factors for Cardiovascular Disease (n = 155) were studied (ages ranging from 45 to 65 years old) and classified according to the Adult Treatment Panel III criterion. A blood sample was taken after a 12-h fasting period, and basal glucose, insulin, thiobarbituric acid reactive substances (TBARS), oxidized LDL (oxLDL), heme oxygenase (HO) activity, lipid profile, and iron nutrition status were determined. Eighty-five subjects were classified as MetS, and 70 non-MetS. Individuals with MetS showed higher Fe storage (high levels of ferritin, total body iron and low transferrin receptor), oxLDL, TBARS, and homeostatic model assessment for insulin resistance levels. The MetS group showed high levels of oxidative stress parameters (HO activity, oxLDL, and TBARS). The presence of MetS showed an association with LDL oxidation risk (multiple lineal regression according to sex and age, p < 0.001). High levels of triglycerides (p < 0.001) and waist circumference (p < 0.012) were associated with oxLDL levels, as well as an association between TBARS and oxLDL with ferritin levels. Through logistic regression analyses, the highest quartile of ferritin was associated with a threefold risk of developing MetS compared to the lowest quartile; also, TBARS showed a 21-fold risk for the development of MetS. Finally, elevated levels of oxidative stress parameters such us oxLDL, TBARS, HO, and Fe storage were associated to MetS.

High levels of hsCRP are associated with carbohydrate metabolism disorder.

AIM: To determine risk parameters associated with high values of high sensitive C-reactive protein (hsCRP) in subjects with different glucose fasting levels. METHODS: Anthropometric parameters, arterial pressure, glycemia, lipid profile, uric acid, and hsCRP were studied in a population of 513 individuals between 40 and 65 years. RESULTS: In total, 349 (68.0%) were normoglycemic (NG); 113 (22.0%) had impaired fasting glucose (IFG); and 51 (9.9%) were diabetic subjects. A multivariate linear regression analysis showed that the natural logarithm of hsCRP was associated significantly with glycemia levels (P = 0.009), uric acid (P = 0.001), diastolic blood pressure (P = 0.011), smoking habit (P = 0.021), BMI (P<0.001), and sex (P<0.001). One-third of the NG subjects had high hsCRP levels. A multiple logistic regression analysis showed that sex and BMI were variables related to high levels of hsCRP in subjects with IFG and NG. In NG subjects, uric acid levels were associated with risk of presenting high hsCRP levels and were higher in women than men. In NG women, ROC curves analysis identified a uric acid level of 3.9 mg/dl as a cut-off point to predict a high value of hsCRP. Those individuals with uric acid values higher than 3.9 mg/dl and normal glycemia had 3.5-fold more risk of having hsCRP levels over 3.0 mg/l. CONCLUSIONS: We sustain that high levels of hsCRP are associated with disturbance in carbohydrate metabolism. In addition, we believe that in low cardiovascular risk population, such as NG women, uric acid levels above 3.9 mg/dl might represent a signal of possible pro-inflammatory state and cardiovascular risk.

Intervention with education and exercise reverses the metabolic syndrome in adults.

About 29% of the adult population of Talca, Chile, suffers from the metabolic syndrome (MS), a value higher than the national prevalence. Evidence indicates that exercise and nutritional changes reduce the predominance of this syndrome. The goal of this study was to evaluate the effects of a structured interventional program of physical activity and nutritional counseling in adults with MS. Fifty-one subjects were studied: 27 were included in the interventional program (I-MS). The control group was formed by 24 individuals who did not participate in the program (NI-MS). We assessed body weight, corporal composition, arterial pressure, glycemia, and lipid profile at baseline and after 18 weeks of treatment. After this period, the I-SM group showed a significant decrease in triglycerides (geometric mean 202.2 to 110.5 mg/dL, P < .001), diastolic blood pressure (mean 85.4 to 79.6 mm Hg, P = .001), waist circumference (mean men 101.5 to 94.1 cm, P < .001; mean women 107.2 to 96.2 cm, P < .001), weight (mean 81.1 to 77.2 kg, P < .001), and body mass index (mean 31.8 to 30.2 kg/m(2), P < .001). In the NI-MS group, the individual parameters did not change significantly. Our results show that a non-pharmacological treatment based on exercise exerts an important beneficial effect in patients with MS, mainly on the waist circumference, blood pressure, and triglycerides.

Inhibitory effect of three C-glycosylflavonoids from Cymbopogon citratus (Lemongrass) on human low density lipoprotein oxidation.

This study assessed the inhibitory effect of three C-glycosylflavonoids from Cymbopogon citratus leaves--isoorientin (1), swertiajaponin (2) and isoorientin 2"-Orhamnoside (3)--on human LDL oxidation. Isolated LDL was incubated with compounds 1-3 and the kinetics of lipid peroxidation were assessed by conjugated diene and malondialdehyde-thiobarbituric acid reactive substances (MDA-TBARS) formation after addition of copper ions. Significant differences (p < 0.05) between the lag time phase of the control and the lag time phase in the presence of the compounds 1 (0.25 microM) and 2 (0.50 microM) were observed. After five hours of incubation all three compounds showed a significant inhibitory effect on MDA-TBARS formation with respect to the control. After six hours of incubation only compound 1 kept a remarkable antioxidant effect. This study demonstrates that isoorientin (1) is an effective inhibitor of in vitro LDL oxidation. As oxidative damage to LDL is a key event in the formation of atherosclerotic lesions, the use of this natural antioxidant may be beneficial to prevent or attenuate atherosclerosis.

Evaluation of metabolic syndrome in adults of Talca city, Chile.

OBJECTIVE: Insulin resistance (IR) is an important risk factor for type 2 Diabetes Mellitus (DM2) and cardiovascular disease (CVD). Metabolic Syndrome (MS) is a clustering of metabolic alterations associated to IR; however, there is no international consensus for defining its diagnosis. Our objective was to evaluate the prevalence and characteristics of MS identified by the ATP III and IDF criteria in adults from Talca city. RESEARCH AND METHODS: We studied 1007 individuals, aged 18-74, and residents from Talca. MS subjects were defined according to ATP III (three altered factors) and IDF criteria (patients with waist circumference >80/90 cm (W/M) and two others altered factors). RESULTS: The prevalence of metabolic syndrome according to the IDF and ATP III criteria was 36.4% and 29.5%, respectively after adjustment for age and sex. The agreement for both criteria was 89%. The prevalence in men was higher than in women for both MS definitions, although not significant. MS probability increased with age, and the highest risk was in the 57-68 age group (ATP-MS) and 53-72 age group (IDF-MS). Hypertension, high triglycerides and abdominal obesity are the most frequent alterations in MS. CONCLUSION: MS prevalence in adults was higher when diagnosed with IDF than with ATP criterion; in both, age is directly related with the MS presence. The MS subjects showed higher levels of blood pressure, waist circumference and plasma triglycerides. Considering our results, it is worrisome that one third of our population has a high risk of developing DM2 and CVD in the future.

Relationship between Apolipoprotein E polymorphism and nephropathy in type-2 diabetic patients.

Twenty to forty percent of type-2 diabetic patients (DM2) present nephropathy. Genetic polymorphism of Apolipoprotein E (Apo E) has been proposed as a risk factor in the development and progression of diabetic nephropathy. The purpose of the study was to evaluate the relationship between Apo E polymorphism and presence of nephropathy in DM2 patients. We studied 85 DM2 patients with a similar nutritional state, environmental and socioeconomic condition and more than 10 years of evolution. They were grouped in DM2 patients with kidney complications (n=56) and without kidney complications (n=29; control group). Apo E genotype was determined by restriction fragment-length polymorphism analysis. A plasmatic biochemical characterization was performed on all the subjects studied. The 85 DM2 patients had arterial hypertension in treatment. The nephropathy diabetic group showed differences (p<0.001) in BMI, systolic blood pressure, glycemia, cholesterol (total, HDL and LDL), HbA1c and creatinine. The e4 allelic frequency was 8% in the nephropathy group versus 25.9% in the control group. Apo e3 allele and E3/3 genotype frequency were higher and E3/4 genotype was lower in the nephropathy group than in controls. These groups also showed differences in total, HDL and LDL cholesterol. DM2 patients without nephropathy presented a higher frequency of e4 allele. These results could suggest a protective role of e4 allele in the development and progression of diabetic nephropathy.

Apolipoprotein E polymorphism in type 2 diabetic patients of Talca, Chile.

Apolipoprotein E (apo E) modulates the metabolism of atherogenic lipoprotein particles and participates in the process of cellular incorporation of specific lipoproteins. Genetic polymorphism of apo E has been reported as an important dyslipidemia genetic marker associated with coronary artery disease. Type 2 diabetes mellitus is a disease with a high incidence and prevalence in the world. The main cause of death in these patients is myocardial stroke and a high incidence of general cardiovascular complications. The purpose of this work was to characterize the genotype of apo E in diabetic patients from Talca, Chile, in order to describe the allelic frequency of the apo E gene and its correlation to the lipids profile. Type 2 diabetic patients (200) were recruited from the Diabetes Program of Talca Hospital, Chile. Apo E genotype was determined by restriction fragment-length polymorphism analysis. A biochemical characterization was performed in all the subjects. Type 2 diabetic patients had elevated levels of glycemia, lipid profile and BMI compared to the control group. The E3/3 genotype and epsilon3 allele had a higher frequency in both groups. The E2/3 and E3/4 genotypes had higher levels of triglyceride (TG) and cholesterol respectively; however, there was not any statistical relationship between them. In conclusion, genotype of apo E in diabetic patients did not differ with healthy; E2/3 and E3/4 genotypes tend to have higher levels of triglyceride and cholesterol respectively. We think that these results corroborate that in the etiology of the dyslipidemia, there is more than one associate genetic marker.