title: Impaired synthesis contributes to diabetes-induced decrease in liver             glutathione.
abstract: Diabetes-induced glutathione (GSH) decrease is usually ascribed to GSH oxidation.             Here we investigate, in streptozotocin-treated rats, if impairment of GSH synthesis             contributes to GSH decrease in diabetic liver, and if antioxidant treatments can             provide protection. Diabetic rats were divided into 3 groups: untreated diabetic             rats (UD); N-acetyl-cysteine (NAC)-treated diabetic rats; taurine (TAU)-treated             diabetic rats; a group of non-streptozotocin-treated rats was used as control             (CTR). All rats were sacrificed at 40 weeks of age. Diabetes induced hepatic glutathione             decrease, but oxidized glutathione (GSSG) did not increase significantly. Accumulations             of cysteine and cysteinyl-glycine in UD suggest respectively decreased glutathione             synthesis and increased loss through the plasma membrane with subsequent degradation.             Decreased expression of γ-glutamyl-cysteine synthetase in UD is consistent with             repressed GSH synthesis. Moreover, diabetes caused increase of GSSG/GSH ratio             and induction of heme oxygenase-1, both signs of oxidative stress. Supplementation             with NAC or TAU resulted in amelioration of glutathione levels, probably depending             on antioxidant activity, more efficient glutathione synthesis and decreased GSH             loss and degradation. In conclusion, impaired synthesis and increased loss and             degradation of GSH appear to contribute to a decrease in GSH levels in diabetic             liver. NAC and TAU are able to partially protect from oxidative stress and GSH             decrease, while enhancing GSH synthesis and restricting GSH loss.
authors.affiliation: Department of Experimental Medicine, Section of General Pathology,                     University of Genova, Genova, Italy.
authors.forename: Anna Lisa
authors.initials: AL
authors.lastname: Furfaro
authors.forename: Mariapaola
authors.initials: M
authors.lastname: Nitti
authors.forename: Barbara
authors.initials: B
authors.lastname: Marengo
authors.forename: Cinzia
authors.initials: C
authors.lastname: Domenicotti
authors.forename: Damiano
authors.initials: D
authors.lastname: Cottalasso
authors.forename: Umberto Maria
authors.initials: UM
authors.lastname: Marinari
authors.forename: Maria Adelaide
authors.initials: MA
authors.lastname: Pronzato
authors.forename: Nicola
authors.initials: N
authors.lastname: Traverso
mesh_terms: D000111:Acetylcysteine / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D019803:Glutathione Disulfide / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D013654:Taurine / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D013654:Taurine; D013311:Streptozocin; D051547:Heme Oxygenase-1; D005978:Glutathione; D019803:Glutathione Disulfide; D000111:Acetylcysteine