8-hydroxy-2--deoxyguanosine and Dyslipidemias

Dyslipidemia is a common complication of chronic kidney disease (CKD) and contributes to cardiovascular morbidity and mortality of CKD patients.. The aim of the present study was to determine whether fluvastatin, which is mostly characterized by its pleiotropic anti-oxidant effects, has renoprotective effects in dyslipidemic patients with CKD.. In 43 dyslipidemic patients with CKD taking fluvastatin 10 mg/day, 20 mg/day or 30 mg/day, renal functions as well as lipid profiles were assessed.. After 3 months of treatment with fluvastatin, LDL-cholesterol level significantly decreased. Serum creatinine level, estimated glomerular filtration rate (eGFR), urinary albumin excretion (UAE), urinary liver-type fatty acid binding protein (L-FABP) level and urinary 8-hydroxydeoxyguanosine (8-OHdG) level did not change in overall patients. However, in patients with microalbuminuria (baseline UAE ≥ 30 mg/g·creatinine; n = 23), the UAE significantly decreased [2.43 ± 0.67 to 1.98 ± 0.80 log(mg/g·creatinine), p = 0.01]. In patients with high L-FABP group (baseline L-FABP ≥ 11 µg/g·creatinine; n = 18), the urinary L-FABP level was significantly decreased (1.52 ± 0.45 to 1.26 ± 0.43 µg/g·creatinine, p < 0.01). In the limited 23 patients with microalbuminuria, the L-FABP level was significantly decreased [1.20 ± 0.62 to 1.03 ± 0.49 log(µg/g·creatinine), p = 0.042], although the LDL-cholesterol level (139 ± 28 to 129 ± 23 mg/dL, p = 0.08) only showed a tendency to decrease. The 8-OHdG level also was significantly decreased (13.6 ± 9.6 to 9.8 ± 3.8 ng/g·creatinine, p = 0.043). In the overall patients, changes in the values for UAE and urinary L-FABP were not correlated with the changes in LDL-levels.. Fluvastatin reduces both UAE and the urinary L-FABP level, and thus, has renoprotective effects, independent of its lipid lowering effects in dyslipidemic patients with CKD.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Aged, 80 and over; Albuminuria; Cholesterol, LDL; Creatinine; Deoxyguanosine; Dyslipidemias; Fatty Acid-Binding Proteins; Fatty Acids, Monounsaturated; Female; Fluvastatin; Glomerular Filtration Rate; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Male; Renal Insufficiency, Chronic; Treatment Outcome

Since co-administration of ezetimibe, a specific inhibitor of cholesterol absorption into the intestine, has been shown to augment lipid-lowering effects of statins, ezetimibe plus statins is a novel therapeutic strategy for the treatment of dyslipidemia in high-risk patients. Statins have been shown to ameliorate renal function and reduce proteinuria in patients with chronic kidney disease (CKD). However, effects of co-administration of ezetimibe with statins on renal damage and dysfunction in CKD patients remain unknown. In this study, we examined whether co-administration of ezetimibe with pitavastatin could augment renoprotective properties of pitavastatin in non-diabetic CKD patients with dyslipidemia. Total cholesterol, LDL-cholesterol and triglycerides levels were reduced more by co-administration of ezetimibe (10mg/day) with pitavastatin (2mg/day) (n=10) than by pitavastatin alone (n=10). In addition, ezetimibe plus pitavastatin treatment produced significant incremental reduction in proteinuria related to pitavastatin therapy alone. In univariate analyses, proteinuria was correlated with plasma levels of total cholesterol, LDL-cholesterol, triglycerides, HDL-cholesterol (inversely), asymmetric dimethylarginine, an endogenous nitric oxide synthase inhibitor, and urinary excretion levels of L-fatty acid binding protein (L-FABP), a marker of tubular injury and 8-hydroxydeoxyguanosine (8-OHdG), an oxidative stress marker. Multiple stepwise regression analysis revealed that LDL-cholesterol (p<0.001) and urinary excretion levels of L-FABP (p=0.001) and 8-OHdG (p<0.001) were independently related to proteinuria (R(2)=0.969). Our present study demonstrated for the first time that co-administration of ezetimibe enhanced proteinuria-lowering effects of pitavastatin in non-diabetic CKD patients partly via a cholesterol-independent manner. Ezetimibe may have pleiotropic actions that could contribute to renoprotective properties of this lipid-lowering agent.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Anticholesteremic Agents; Arginine; Azetidines; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Deoxyguanosine; Drug Therapy, Combination; Dyslipidemias; Ezetimibe; Fatty Acid-Binding Proteins; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kidney Diseases; Male; Middle Aged; Proteinuria; Quinolines; Severity of Illness Index; Treatment Outcome; Triglycerides

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Case-Control Studies; Chromosomes, Human; Cytokinesis; DNA Damage; Dyslipidemias; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Micronucleus Tests; Middle Aged

To explore the association between dyslipidemia and the level of 8-OHdG/Cr in urine among a population exposed to chronic arsenic.. Four hundred and seven subjects were randomly selected in an arsenic-affected area in Inner Mongolia. After blood biochemical examination, all the subjects were divided into 4 groups based on the results of total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C)and low density lipoprotein cholesterol (LDL-C). The groups consisted of hypercholesterolemia, HDL-C ratio anomaly, combined hypercholesterolemia and HDL-C ratio anomaly, as well as a normal lipid group. Urine samples were collected and 8-OHdG/Cr was measured using the ELISA method. A generalized linear mixed model was used to analyze the association between dyslipidemia and 8-OHdG/Cr.. The levels of 8-OHdG/Cr as 55.73 (39.90-79.94) ng/mg, 58.08 (44.94-69.91)ng/mg, 65.28 (49.29-92.95) ng/mg and 51.43 (36.86-68.57) ng/mgin the HDL-C ratio anomaly, hypercholesterolemia, combined hypercholesterolemia and HDL-C ratio anomaly groups and the control group, respectively, which showed significant differences on the levels of 8-OHdG/Cr in the four groups(P = 0.006). From the linear regression analysis results showed that the 8-OHdG/Cr level in combined hypercholesterolemia and HDL-C ratio anomaly group was higher (4.25 ± 0.55 ng/mg) than in the control group (3.96 ± 0.55 ng/mg) (P = 0.018). After adjusting for important covariates, there was a linear trend between the levels of 8-OHdG/Cr and dyslipidemia (P = 0.016).. Data from our study showed a linear relation between hypercholesterolemia, HDL-C ratio anomaly and the 8-OHdG/Cr level, suggesting that dyslipidemia was associated with oxidative DNA damage among those .

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adolescent; Adult; Aged; Arsenic Poisoning; Cholesterol, HDL; Chronic Disease; Deoxyguanosine; DNA Damage; Dyslipidemias; Female; Humans; Male; Middle Aged; Triglycerides; Young Adult

Diabetes mellitus is characterized by oxidative stress, which in turn determines endothelial dysfunction. Gliclazide is a sulphonylurea antidiabetic drug with antioxidant effects due to its azabicyclo-octyl ring. It has been reported to potentially protect the vasculature through improvements in plasma lipid levels and platelet function. We hypothesized that gliclazide has a beneficial effect on endothelial function in Goto-Kakizaki rats (GK), an animal model of type 2 diabetes fed an atherogenic diet for 4 months. We evaluated the influence of gliclazide on both metabolic and oxidative status and NO-mediated vasodilation. GKAD rats showed increased oxidative stress and impaired endothelium-dependent vasodilation. GKAD rats treated with gliclazide showed increased sensitivity to NO-mediated vasodilation, a significant decrease in fasting glycemia and insulinemia, and a significant decrease in systemic oxidative stress. In conclusion, our results suggest that gliclazide treatment improves NO-mediated vasodilation in diabetic GK rats with dyslipidemia probably due to its antioxidant effects, although we cannot rule out substantial benefits due to a reduction in fasting blood glucose. The availability of a compound that simultaneously decreases hyperglycemia, hyperinsulinemia, and inhibits oxidative stress is a promising therapeutic candidate for the prevention of vascular complications of diabetes.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Acetylcholine; Animals; Antioxidants; Body Weight; Deoxyguanosine; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Dietary Fats; Disease Models, Animal; Dyslipidemias; Gliclazide; Hypoglycemic Agents; Nitric Oxide; Oxidative Stress; Rats; Rats, Mutant Strains; Rats, Wistar; Vasodilation; Vasodilator Agents