beta-carotene and Diabetic-Nephropathies

Diabetic nephropathy (DN), a major cause of morbidity and mortality in diabetes, will develop within a subset of type 1 diabetes mellitus (T1DM) patients, and oxidative stress has been implicated in its pathogenesis. To investigate the relationship between indicators of early DN stages (hyperfiltration estimated by creatinine clearance > or =150 ml/min per 1.73 m(2), microalbuminuria) and oxidative stress, a prospective study was conducted in 29 T1DM patients (age 13.89 +/- 4.61 years) and 18 control subjects (age 13.23 +/- 3.99 years). Blood samples were collected to assay for biomarkers of oxidative stress (malondialdehyde and carbonyl groups) and antioxidants (glutathione peroxidase, reduced glutathione, alpha-tocopherol, and beta-carotene). With respect to control subjects, in T1DM patients, an increase was found in biomarkers of oxidative stress (p < 0.05), mainly due to the group of subjects with hyperfiltration, and a decrease in the ratio alpha-tocopherol/lipids (p < 0.05). In multiple regression analyses, age at disease onset, glycated hemoglobin, microalbuminuria, and oxidative stress biomarkers remained as explicative variables of hyperfiltration (R (2) adjusted = 0.731, p = 0.000). These findings support the importance of the oxidative damage to lipids and proteins, which is linked to hyperfiltration and which could contribute to the development of DN in patients with T1DM.

Topics: Adolescent; Age of Onset; Albuminuria; alpha-Tocopherol; Antioxidants; beta Carotene; Biomarkers; Child; Child, Preschool; Creatinine; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Female; Glomerular Filtration Rate; Glutathione; Glutathione Peroxidase; Humans; Male; Malondialdehyde; Oxidants; Oxidative Stress; Prospective Studies; Young Adult

Oxidative stress is implicated as an important mechanism by which diabetes causes nephropathy. Astaxanthin, which is found as a common pigment in algae, fish, and birds, is a carotenoid with significant potential for antioxidative activity. In this study, we examined whether chronic administration of astaxanthin could prevent the progression of diabetic nephropathy induced by oxidative stress in mice. We used female db/db mice, a rodent model of type 2 diabetes, and their non-diabetic db/m littermates. The mice were divided into three groups as follows: non-diabetic db/m, diabetic db/db, and diabetic db/db treated with astaxanthin. Blood glucose level, body weight, urinary albumin, and urinary 8-hydroxydeoxyguanosine (8-OHdG) were measured during the experiments. Histological and 8-OHdG immunohistochemical studies were performed for 12 weeks from the beginning of treatment. After 12 weeks of treatment, the astaxanthin-treated group showed a lower level of blood glucose compared with the non-treated db/db group; however, both groups had a significantly high level compared with the db/m mice. The relative mesangial area calculated by the mesangial area/total glomerular area ratio was significantly ameliorated in the astaxanthin-treated group compared with the non-treated db/db group. The increases in urinary albumin and 8-OHdG at 12 weeks of treatment were significantly inhibited by chronic treatment with astaxanthin. The 8-OHdG immunoreactive cells in glomeruli of non-treated db/db mice were more numerous than in the astaxanthin-treated db/db mice. In this study, treatment with astaxanthin ameliorated the progression and acceleration of diabetic nephropathy in the rodent model of type 2 diabetes. The results suggested that the antioxidative activity of astaxanthin reduced the oxidative stress on the kidneys and prevented renal cell damage. In conclusion, administration of astaxanthin might be a novel approach for the prevention of diabetes nephropathy.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Albuminuria; Animals; beta Carotene; Deoxyguanosine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Models, Animal; Female; Kidney; Mice; Mice, Mutant Strains; Reference Values; Regression Analysis; Tissue Distribution; Xanthophylls

We aimed to examine the relationship of serum lipids, lipoproteins, apolipoproteins and antioxidants with renal dysfunction as measured by urinary excretion of albumin and of retinol binding protein (RBP) in insulin-dependent diabetes mellitus (IDDM). We studied 121 patients with IDDM. Glomerular function was assessed as the urinary albumin/creatinine ratio (UA/UC), and tubular function as the urinary retinol-binding protein/creatinine ratio (UR/UC), both measured in three early morning spot urine samples. The mean (range) UA/UC was 1.95 mg/mmol (0.3-476.5) and UR/UC was 17.5 micrograms/mmol (1.0-1853.8). 17% of the patients had a UA/UC > 3 mg/mmol and 33% had a UR/UC > 20 micrograms/mmol. Significant positive correlations were observed between both UA/UC and UR/UC and the following: serum total cholesterol (P < 0.005); triglycerides (P < 0.001); apolipoproteins A-I (P < 0.05), A-II (P < 0.02) and B (P < 0.002); glycated haemoglobin (P < 0.002). No significant associations were found with serum vitamin E, beta-carotene or total antioxidant activity. In multiple regression, only UA/UC was independently associated with serum apo B and cholesterol concentrations. In conclusion, in IDDM glomerular dysfunction, as measured by UA/UC, is associated with elevated serum cholesterol, triglycerides, apo B, apo A-I and apo A-II, but not with HDL cholesterol or antioxidant status. Tubular dysfunction tends to occur with increasing albuminuria, but it is not independently associated with serum lipid, lipoprotein, apolipoprotein or antioxidant levels.

Topics: Adult; Aged; Albuminuria; Antioxidants; Apolipoprotein A-I; Apolipoprotein A-II; Apolipoproteins B; beta Carotene; Biomarkers; Blood Pressure; Cholesterol; Cholesterol, HDL; Creatinine; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Female; Glycated Hemoglobin; Humans; Kidney Glomerulus; Kidney Tubules; Lipoprotein(a); Lipoproteins; Male; Middle Aged; Regression Analysis; Retinol-Binding Proteins; Triglycerides; Vitamin E