title: Mitochondrial dysfunction in brain cortex mitochondria of STZ-diabetic rats: effect of l-Arginine.
abstract: Mitochondrial dysfunction has been implicated in many diseases, including diabetes. It is well known that oxygen free radical species are produced endogenously by mitochondria, and also nitric oxide (NO) by nitric oxide synthases (NOS) associated to mitochondrial membranes, in consequence these organelles constitute main targets for oxidative damage. The aim of this study was to analyze mitochondrial physiology and NO production in brain cortex mitochondria of streptozotocin (STZ) diabetic rats in an early stage of diabetes and the potential effect of L-arginine administration. The diabetic condition was characterized by a clear hyperglycaemic state with loose of body weight after 4 days of STZ injection. This hyperglycaemic state was associated with mitochondrial dysfunction that was evident by an impairment of the respiratory activity, increased production of superoxide anion and a clear mitochondrial depolarization. In addition, the alteration in mitochondrial physiology was associated with a significant decrease in both NO production and nitric oxide synthase type I (NOS I) expression associated to the mitochondrial membranes. An increased level of thiobarbituric acid-reactive substances (TBARS) in brain cortex homogenates from STZ-diabetic rats indicated the presence of lipid peroxidation. L-arginine treatment to diabetic rats did not change blood glucose levels but significantly ameliorated the oxidative stress evidenced by lower TBARS and a lower level of superoxide anion. This effect was paralleled by improvement of mitochondrial respiratory function and a partial mitochondrial repolarization.In addition, the administration of L-arginine to diabetic rats prevented the decrease in NO production and NOSI expression. These results could indicate that exogenously administered L-arginine may have beneficial effects on mitochondrial function, oxidative stress and NO production in brain cortex mitochondria of STZ-diabetic rats.
authors.affiliation: Cátedra de Biología Celular y Molecular, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, C1113AAD, Buenos Aires, Argentina.
authors.forename: M Del Carmen
authors.initials: Mdel C
authors.lastname: Ortiz
authors.forename: Silvia
authors.initials: S
authors.lastname: Lores-Arnaiz
authors.forename: M Florencia
authors.initials: MF
authors.lastname: Albertoni Borghese
authors.forename: Sabrina
authors.initials: S
authors.lastname: Balonga
authors.forename: Agustina
authors.initials: A
authors.lastname: Lavagna
authors.forename: Ana Laura
authors.initials: AL
authors.lastname: Filipuzzi
authors.forename: Daniela
authors.initials: D
authors.lastname: Cicerchia
authors.forename: Monica
authors.initials: M
authors.lastname: Majowicz
authors.forename: Juanita
authors.initials: J
authors.lastname: Bustamante
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D001835:Body Weight; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013311:Streptozocin
chemical_list: D001786:Blood Glucose; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D013311:Streptozocin; D001120:Arginine