Advanced glycation end‐products in sickle cell anaemia

Abstract

Summary Tissue accumulation of advanced glycation end‐products (AGEs) has been implicated in the oxidant‐induced vascular pathology of diabetes and other diseases. Because homozygous sickle cell anaemia (SCA) is a state of oxidative stress, we tested the hypothesis that circulating AGE levels are elevated in SCA. Blood was obtained from age‐ and race‐matched children classified as either non‐sickle cell controls, SCA without vaso‐occlusive crisis (SCA − VOC), or SCA with vaso‐occlusive crisis (SCA + VOC). Plasma and red blood cell (RBC) AGE levels were measured by immunoassay. RBC levels of reduced (GSH) and oxidized (GSSG) glutathione were measured by capillary electrophoresis as an indicator of endogenous antioxidant status. The results showed that plasma AGE levels and the rate of RBC AGE accumulation were significantly higher in patients with SCA compared with controls. GSH was not different between groups but was significantly inversely correlated with plasma AGEs in both controls and patients with SCA. GSSG was significantly lower and GSH/GSSG higher in SCA + VOC patients, suggesting that GSH/GSSG might be an objective indicator of acute VOC or a risk factor for VOC. We conclude that circulating AGE levels are strongly influenced by endogenous antioxidant status and may play a role in the vascular pathology of SCA.

Validation study to compare effects of processing protocols on measured Nɛ-(carboxymethyl)lysine and Nɛ-(carboxyethyl)lysine in blood

“…A PubMed search shows that in the 1980s, 1990s, and 2000s, the number of articles on AGEs was 21, 978, and >3700, respectively. Epidemiological studies have suggested that individuals with higher elevated circulating CML, are at greater risk of arterial stiffness, (12) chronic kidney disease, (13) anemia, (14) cardiovascular and all-cause mortality. (15) The data provided here support the use of stored samples, regardless of collection and storage method, from other epidemiological studies for the analysis of CML and CEL to further examine the association between AGEs and disease risk.…”

Biomarkers for Oxidative Stress: Clinical Application in Pediatric Medicine

“…Gastrointestinal/Hepatologic: autoimmune hepatitis [38], chronic constipation [112], inflammatory bowel disease [47], nonalcoholic fatty liver disease [75,106], viral hepatitis [19], Wilson disease [78] Genetic: Cockayne syndrome [49], Down syndrome [54,57], Zellweger syndrome [44] Hematologic: acute leukemia [52,53,88], β-thalassemia [45], erythropoietic protoporphyria [104], Fanconi anemia [72], sickle cell anemia [93] Infectious: acute bronchiolitis [70], acute infectious mononucleosis [48], acute otitis media [102], acute tonsillitis [102], adenovirus infection [48], chronic nail candidiasis [80], chronic otitis media [87], chronic tonsillitis [62,82] [90], inflammatory myopathy [60], selenium-deficient skeletal muscle disorder [59], spinal muscular atrophy [24], traumatic brain injury [36,46] Investigation of the role of oxidative stress in pediatric diseases requires information about the oxidative stress status of young populations. It will be possible to evaluate the contribution of oxidative stress to various pediatric diseases and establish better approaches for each disease when we know normal levels of oxidative stress in children and adolescents.…”

Erythrocyte NADPH oxidase activity modulated by Rac GTPases, PKC, and plasma cytokines contributes to oxidative stress in sickle cell disease

“…[3][4][5] RBC and other cell types show evidence of lipid peroxidation and oxidative damage to structural proteins. [6][7][8] Additionally, plasma from SCD patients has elevated levels of advanced glycation end products 9,10 and products of lipid peroxidation (F-2 isoprostanes, malonaldehyde, and 4-hydroxynonenal), [11][12][13] all of which are markers of oxidative stress. There are several postulated mechanisms for the increased oxidative stress in patients with SCD.…”