Homocysteine and inflammation as main determinants of oxidative stress in the elderly |
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| Authors: | Emilie Ventura Richard Durant Audrey Jaussent Marie-Christine Picot Marion Morena Stéphanie Badiou Anne-Marie Dupuy Claude Jeandel Jean-Paul Cristol |
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| Institution: | 1. 5th Department of Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania;2. Department of Medical Genetics, Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania;3. Department of Pharmacology, Toxicology and Clinical Pharmacology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania;4. Department of Pharmaceutical Biochemistry and Clinical Laboratory, Faculty of Pharmacy, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania;5. Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania;6. Department of Medical Biochemistry, Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania;1. Department of Clinical Oncology, Hospital Israelita Albert Einstein, Sao Paulo, Brazil;2. Department of Geriatrics Oncology, Hospital Israelita Albert Einstein and Universidade de Sao Paulo (USP/ICESP), Sao Paulo, Brazil;3. Department of Radiation Oncology, Hospital Israelita Albert Einstein, Sao Paulo, Brazil;4. Department of Neuro-oncology, Hospital Israelita Albert Einstein, Sao Paulo, Brazil |
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| Abstract: | Oxidative stress is commonly observed in the elderly and could be involved in age-related diseases. However, the determinants of superoxide anion overproduction are not clearly understood. Superoxide anion production was evaluated using a lucigenin-based chemiluminescence method in 478 elderly subjects (304 women, 174 men; 79.5 ± 7.1 years). Homocysteine (HCy) metabolism (homocysteinemia, vitamin B12, plasma, and erythrocyte folates), inflammation (CRP, fibrinogen, α-1 acid glycoprotein), lipid parameters (total cholesterol, triglycerides, HDL and LDL cholesterol), and nutritional parameters (albumin, transthyretin) were determined. The results show that HCy levels (p < 0.001) and superoxide anion production (p = 0.04) increase with aging, but CRP does not. Highest HCy (> 20 μM) (OR 1.83 (1.09–3.07), p = 0.02) and CRP over 5 mg/L (adjusted OR 2.01 (1.15–3.51), p = 0.01) are the main determinants in superoxide anion production in the elderly. These clinical data are confirmed in an in vitro study using THP-1 monocyte-like cells. Incubation with HCy thiolactone (HTL) (0–200 μM) and LPS (0–20 ng/ml) dramatically enhances NADPH oxidase expression and activation. Moreover, a synergic action was evidenced for low concentrations of HTL (20 μM) and LPS (5 ng). Taken together, the clinical data and in vitro experiments support the hypothesis that moderate homocysteinemia and low-grade inflammation synergically enhance NADPH oxidase activity in the elderly. |
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