Increased oxidative stress in foam cells obtained from hemodialysis patients.

Premature atherosclerosis represents the main cause of mortality among end-stage renal disease patients (ESRD). Increased inflammation and oxidative stress are involved in initiation and progression of the atherosclerotic plaque. As foam cells are capable of producing significant amounts of inflammatory mediators and free radicals, we hypothesized that foam cells from uremic patients could produce more inflammation and oxidative stress than foam cells from normal people and be, somehow, involved in the accelerated atherosclerosis of uremia. To test this hypothesis, the levels of a few markers of inflammation and oxidative stress: Tumor necrosis factor-α, inducible nitric oxide synthase, malondialdehyde, nitric oxide by-products were measured in the supernatants of macrophage-derived foam cells cultures from 18 hemodialysis patients and 18 apparently healthy individuals controls. Malondialdehyde levels in the supernatant of cell cultures (macrophages stimulated or not with native and oxidized lipoprotein) were significantly increased in uremic patients; no statistically significant difference was found between the supernatant concentrations of nitric oxide by-products, inducible nitric oxide synthase activity, and tumor necrosis factor-α between patients and controls. Our results, obtained with human macrophages and macrophage-derived foam cells, are compatible with the theory that increased cellular oxidative stress and inflammatory activity in ESRD patients could accelerate the atherosclerotic process. The present culture protocol showed it is possible to use human mononuclear cells to evaluate the oxidative metabolism of foam cells, which are considered to be the initial step of atherosclerotic lesions.

[Effects of ramipril and simvastatin on the oxidative stress of diabetic rats]. / Efeito do ramipril e da sinvastatina sobre o estresse oxidativo de ratos diabéticos.

OBJECTIVE: To evaluate if ramipril, with or without simultaneous use of simvastatin, would be capable of reducing oxidative stress of streptozotocin (STZ) induced diabetic rats. METHODS: The drugs were given to the diabetic rats for 2 weeks; oxidative stress was measured by dosage of total plasma antioxidant capacity (TRAP) and malondialdehyde (MDA). RESULTS: Ramipril, used alone, was capable of significantly increasing the antioxidative defenses of the diabetic rat; simvastatin, given alone or combined with ramipril in separate administrations, did not produce any significant effect on the oxidative stress; concomitant administration of ramipril and simvastatin significantly reduced the antioxidative plasmatic defenses of rats with chemically induced diabetes mellitus CONCLUSIONS: Our data corroborate the positive effect of ramipril upon plasma antioxidative defenses but did not confirm a possible beneficial effect of simvastatin in the model. More research is needed to clarify the paradoxal TRAP reduction verified with simultaneous administration of the drugs.

Efeito do ramipril e da sinvastatina sobre o estresse oxidativo de ratos diabéticos / Effects of ramipril and simvastatin on the oxidative stress of diabetic rats

OBJETIVO: Avaliar se o ramipril, isoladamente ou em combinação com a sinvastatina, seria capaz de reduzir o estresse oxidativo de ratos diabéticos pela estreptozotocina (STZ). MÉTODOS: As drogas foram administradas a ratos diabéticos por duas semanas; o estresse oxidativo foi medido por dosagem de capacidade antioxidante total plasmática (TRAP) e malonaldeído (MDA). RESULTADOS: O ramipril usado isoladamente foi capaz de aumentar significativamente as defesas antioxidantes do rato diabético; a sinvastatina isoladamente ou combinada ao ramipril em tomadas separadas não produziu efeito significativo sobre o estresse oxidativo; a administração simultânea de ramipril e sinvastatina reduziu as defesas antioxidantes plasmáticas de ratos com diabetes melito químico. CONCLUSÕES: Os dados do presente estudo corroboram o efeito positivo do ramipril sobre a defesa antioxidante do plasma, mas não confirmam um possível efeito benéfico da sinvastatina no modelo. Pesquisas adicionais são necessárias para clarificar a paradoxal redução da TRAP verificada pela administração simultânea das drogas.

OBJECTIVE: To evaluate if ramipril, with or without simultaneous use of simvastatin, would be capable of reducing oxidative stress of streptozotocin (STZ) induced diabetic rats. METHODS: The drugs were given to the diabetic rats for 2 weeks; oxidative stress was measured by dosage of total plasma antioxidant capacity (TRAP) and malondialdehyde (MDA). RESULTS: Ramipril, used alone, was capable of significantly increasing the antioxidative defenses of the diabetic rat; simvastatin, given alone or combined with ramipril in separate administrations, did not produce any significant effect on the oxidative stress; concomitant administration of ramipril and simvastatin significantly reduced the antioxidative plasmatic defenses of rats with chemically induced diabetes mellitus CONCLUSIONS: Our data corroborate the positive effect of ramipril upon plasma antioxidative defenses but did not confirm a possible beneficial effect of simvastatin in the model. More research is needed to clarify the paradoxal TRAP reduction verified with simultaneous administration of the drugs.

Metformin increases HDL3-cholesterol and decreases subcutaneous truncal fat in nondiabetic patients with HIV-associated lipodystrophy.

The purpose of this study was to assess metformin effects on high-density lipoprotein (HDL) composition of patients with HIV-associated lipodystrophy (LDHIV). Twenty-four adult outpatients were enrolled to receive metformin (1700 mg/d) during 6 months, but 2 were lost to follow-up and 6 stopped the drug due to adverse events (gastrointestinal in 5, and excessive weight loss in 1). From the 16 subjects who completed the study, 69% were female. At baseline, 3 and 6 months, we assessed: weight, waist and hip circumferences, blood pressure, fasting glucose and insulin, homeostasis model assessment of insulin resistance (HOMA2-IR), lipids, and HDL subfractions by microultracentrifugation. At 0 and 6 months, body fat distribution was assessed by computed tomography (CT) scan (L4 and middle femur). Metformin use was associated with reduction of mean weight (-2.4Kg at 6 months; p < 0.001), body mass index, waist, waist-to-hip ratio and a marked decrease in blood pressure (p < 0.001). Subcutaneous (p = 0.01) and total abdominal fat (p = 0.002) were reduced, but no change was found in visceral or thigh fat. No difference was detected on plasma glucose, insulin, HOMA2-IR, cholesterol or triglycerides, except for an increase in HDL3-cholesterol (from 21 mg/dL to 24 mg/dL, p = 0.002) and a reduction of nascent HDL (the fraction of plasma HDL-cholesterol not associated to subfractions HDL2 or HDL3) (p = 0.008). Adverse effects were very common, but most were gastrointestinal and mild. Thus, metformin use in LDHIV increases HDL3-cholesterol (probably due to improved maturation of HDL) and decreases blood pressure, weight, waist, and subcutaneous truncal fat, making this an attractive option for preventing cardiovascular disease in this population.