Oxidized LDL (oxLDL) and nitric oxide (NO) exert contradictory actions within the vascular endothelium microenvironment influencing key events in atherogenesis. OxLDL and NO are so far regarded as representative parameters of oxidative stress and endothelial dysfunction, new targets in prevention, diagnosis and therapy of cardiovascular diseases, and also as candidate biomarkers in evaluating the human biological age. The aim of this review is to explore recent literature on molecular mechanisms and pathophysiological relationships between LDL oxidation, NO synthesis and vascular endothelium function/dysfunction in ageing, focusing on the following aspects: (1) the impact of metabolic status on both LDL oxidation and NO synthesis in relation with oxidative stress, (2) the use of oxidized LDL and NO activity as biomarkers in human studies reporting on cardiovascular outcomes, and (3) evidences supporting the importance of oxidized LDL and NO activity as relevant biomarkers in vascular ageing and age-related diseases.
Protein carbonyls are widely analysed as a measure of protein oxidation. Several different methods exist for their determination. A previous study had described orders of magnitude variance that existed when protein carbonyls were analysed in a single laboratory by ELISA using different commercial kits. We have further explored the potential causes of variance in carbonyl analysis in a ring study. A soluble protein fraction was prepared from rat liver and exposed to 0, 5 and 15 min of UV irradiation. Lyophilised preparations were distributed to six different laboratories that routinely undertook protein carbonyl analysis across Europe. ELISA and Western blotting techniques detected an increase in protein carbonyl formation between 0 and 5 min of UV irradiation irrespective of method used. After irradiation for 15 min, less oxidation was detected by half of the laboratories than after 5 min irradiation. Three of the four ELISA carbonyl results fell within 95% confidence intervals. Likely errors in calculating absolute carbonyl values may be attributed to differences in standardisation. Out of up to 88 proteins identified as containing carbonyl groups after tryptic cleavage of irradiated and control liver proteins, only seven were common in all three liver preparations. Lysine and arginine residues modified by carbonyls are likely to be resistant to tryptic proteolysis. Use of a cocktail of proteases may increase the recovery of oxidised peptides. In conclusion, standardisation is critical for carbonyl analysis and heavily oxidised proteins may not be effectively analysed by any existing technique.
The major protective role of adiponectin versus stress related to an impaired glucose and lipid metabolism suggests that adiponectin plays a critical role in adiposity-related metabolic stress and redox homeostasis.
Insulin and leptin have an overlapping anorexigenic action as well as opposite effects on glucose and lipid metabolism. The study focuses on the biochemical and clinical relevance of new indices of insulin-leptin axis utilized in the study of the relationships between leptinemia, insulin sensitivity and oxidative stress, in elderly subjects with metabolic syndrome. We conducted clinical studies on elderly people with metabolic syndrome versus control subjects by creating new insulin-adipogenic indices, namely Insulin-to-Leptin Ratio (ILR) and Insulin-Adipogenic Resistance index (IAR-index). Inflammation and oxidative stress biomarkers evaluated were the high-sensitivity C-reactive protein (hsCRP), the advanced oxidation protein products (AOPP), and the serum antioxidant capacity measured as ferric reducing antioxidant potential (FRAP). The metabolic syndrome group showed significantly (p<0.01) lower levels of ILR and not significant (p=0.09) higher values of IAR-index, as compared to the control group. In metabolic syndrome subjects, the IAR-index was significantly positively correlated with uric acid (r=0.313, p<0.05), FRAP (r=0.347, p<0.05) and AOPP (r=0.677, p<0.01), and negatively correlated with HDL-cholesterol (r=- 0.340, p<0.05) as well as with the ratio FRAP/uric acid (r=- 0.315, p<0.05). ILR and IAR-index reflected the biological state of adipose and pancreatic β-cells and seem to depict the adipo-insular axis status related to metabolic and oxidative stress better than individual markers. Therefore, ILR and IAR-index could represent integrated high-potential biomarkers for disease and patient stratification.
Ionizing radiation induces genomic instability in living organisms, and several studies reported an ageing-dependent radiosensitivity. Chemical compounds, such as scavengers, radioprotectors, and modifiers, contribute to reducing the radiation-associated toxicity. These compounds are often antioxidants, and therefore, in order to be effective, they must be present before or during exposure to radiation. However, not all antioxidants provide radioprotection. In this study, we investigated the effects of procaine and of a procaine-based product Gerovital H3 (GH3) on the formation of endogenous and X-ray-induced DNA strand breaks in peripheral blood mononuclear cells (PBMCs) isolated from young and elderly individuals. Interestingly, GH3 showed the strongest radioprotective effects in PBMCs from young subjects, while procaine reduced the endogenous amount of DNA strand breaks more pronounced in aged individuals. Both procaine and GH3 inhibited lipid peroxidation, but procaine was more effective in inhibiting mitochondria free radicals’ generation, while GH3 showed a higher antioxidant action on macrophage-induced low-density lipoprotein oxidation. Our findings provide new insights into the mechanisms underlying the distinct effects of procaine and GH3 on DNA damage.
Erythropoietin (EPO), a key hormone involved in red blood cell formation has been recently acknowledged for its pleiotropic actions and protective role in ageing and various pathological conditions concurrent with oxidative stress, vascular diseases and metabolic abnormalities such as diabetes mellitus. The aim of the study was to evaluate the relationship between circulating erythropoietin levels and oxidative stress biomarkers, in elderly with type 2 diabetes (T2DM). The study was carried out in 67 subjects with T2DM (69 ± 5 years; n = 37) without anemia, and aged-matched controls (70 ± 6 years; n = 30). EPO serum levels, erythrocyte susceptibility to lipid peroxidation (ESP) and total antioxidant capacity (TAC) were evaluated. Lower EPO levels (p < 0.01) and higher ESP values (p < 0.001) were found in T2DM group, compared to healthy subjects. EPO levels showed significant negative associations with ESP, both in T2DM subjects (r = -0.565; p < 0.001) and in all study population (r = -0,600; p < 0,001; n = 67). In conclusion, we provide new data regarding the cytoprotective effect of EPO exerted at systemic level on erythrocyte membrane, in the particular state of impaired glucose metabolism associated with oxidative stress, in the elderly.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.