title: Oxidative stress improvement is associated with increased levels of taurine in CKD patients undergoing lipid-lowering therapy.
abstract: Lipid-lowering therapy has been reported to reduce several oxidative stress (OS) markers in hypercholesterolemia. Since OS is frequently associated with renal dysfunction, we aimed to investigate the effect of hypolipidemic drugs on oxidative stress and plasma taurine (Tau), a sulfur amino acid with a marked antioxidant effect, in chronic kidney disease (CKD). We enrolled 30 CKD randomized to receive three different hypolipidemic regimens for 12 months: simvastatin alone (40 mg/day) or ezetimibe/simvastatin combined therapy (10/20 or 10/40 mg/day). Low molecular weight (LMW) thiols including homocysteine, cysteine, cysteinylglycine, glutathione, and glutamylcysteine in their reduced and total form and oxidative stress indices as malondialdehyde (MDA) and allantoin/uric acid (All/UA) ratio were also evaluated. Tau concentration significantly increased throughout the therapy. The rise of taurine was more striking for the group with the concomitant administration of ezetimibe/simvastatin 10/40 mg/day (+31.6% after 1 year of therapy). A significant decrease of both MDA and All/UA ratio was observed during therapy for all patients (-19% for both MDA and All/UA ratio) with a more pronounced effect in patients treated with ezetimibe/simvastatin 10/40 mg/day (-26% for MDA and -28% for All/UA ratio). Besides, an increase of thiols reduced forms was found (+20.7% of LMW thiols redox status) with a greater effect in subjects treated with ezetimibe/simvastatin 10/40 mg/day (+24.7%). Moreover, we demonstrated that oxidative stress improvement during therapy was correlated with increased taurine levels. We hypothesize that taurine may be responsible for the oxidative stress improvement observed during lipid-lowering treatment through the reduction of superoxide anion production at the respiratory chain activity level.
authors.affiliation: Porto Conte Ricerche Srl, Tramariglio, Alghero, Sassari, Italy. angelozinellu@libero.it
authors.forename: Angelo
authors.initials: A
authors.lastname: Zinellu
authors.forename: Salvatore
authors.initials: S
authors.lastname: Sotgia
authors.forename: Giacomina
authors.initials: G
authors.lastname: Loriga
authors.forename: Luca
authors.initials: L
authors.lastname: Deiana
authors.forename: Andrea Ercole
authors.initials: AE
authors.lastname: Satta
authors.forename: Ciriaco
authors.initials: C
authors.lastname: Carru
mesh_terms: D000368:Aged; D000481:Allantoin / Q000097:blood; D001384:Azetidines / Q000494:pharmacology* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004338:Drug Combinations; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D000960:Hypolipidemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D019821:Simvastatin / Q000494:pharmacology* / Q000627:therapeutic use; D013438:Sulfhydryl Compounds / Q000097:blood; D013481:Superoxides / Q000097:blood; D013654:Taurine / Q000097:blood*; D014527:Uric Acid / Q000097:blood
chemical_list: D001384:Azetidines; D004338:Drug Combinations; D000960:Hypolipidemic Agents; D013438:Sulfhydryl Compounds; D013481:Superoxides; D013654:Taurine; D014527:Uric Acid; D000481:Allantoin; D008315:Malondialdehyde; D019821:Simvastatin; D000069438:Ezetimibe