title: Brain catalase in the streptozotocin-rat model of sporadic Alzheimer's disease treated with the iron chelator-monoamine oxidase inhibitor, M30.
abstract: Low intracerebroventricular (icv) doses of streptozotocin (STZ) produce regionally specific brain neurochemical changes in rats that are similar to those found in the brain of patients with sporadic Alzheimer's disease (sAD). Since oxidative stress is thought to be one of the major pathologic processes in sAD, catalase (CAT) activity was estimated in the regional brain tissue of animals treated intracerebroventricularly with STZ and the multitarget iron chelator, antioxidant and MAO-inhibitor M30 [5-(N-methyl-N-propargylaminomethyl)-8-hydroxyquinoline]. Five-day oral pre-treatment of adult male Wistar rats with 10 mg/kg/day M30 dose was followed by a single injection of STZ (1 mg/kg, icv). CAT activity was measured colorimetrically in the hippocampus (HPC), brain stem (BS) and cerebellum (CB) of the control, STZ-, M30- and STZ + M30-treated rats, respectively, 4 weeks after the STZ treatment. STZ-treated rats demonstrated significantly lower CAT activity in all three brain regions in comparison to the controls (p < 0.05 for BS and CB, p < 0.01 for HPC). M30 pre-treatment of the control rats did not influence the CAT activity in HPC and CB, but significantly increased it in BS (p < 0.05). M30 pre-treatment of STZ-treated rats significantly increased CAT activity in the HPC in comparison to the STZ treatment alone (p < 0.05) and normalized to the control values. These findings are in line with the assumption that reactive oxygen species contribute to the pathogenesis of STZ in a rat model of sAD and indicate that multifunctional iron chelators such as M30 might also have beneficial effects in this non-transgenic sAD model.
authors.affiliation: Department of Chemistry, Faculty of Science, University of Sarajevo, Zmaja od Bosne 33-35, 71 000, Sarajevo, Bosnia and Herzegovina, esofic@pmf.unsa.ba.
authors.forename: E
authors.initials: E
authors.lastname: Sofic
authors.forename: M
authors.initials: M
authors.lastname: Salkovic-Petrisic
authors.forename: I
authors.initials: I
authors.lastname: Tahirovic
authors.forename: A
authors.initials: A
authors.lastname: Sapcanin
authors.forename: S
authors.initials: S
authors.lastname: Mandel
authors.forename: M
authors.initials: M
authors.lastname: Youdim
authors.forename: P
authors.initials: P
authors.lastname: Riederer
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002374:Catalase / Q000378:metabolism*; D003124:Colorimetry; D004195:Disease Models, Animal; D006912:Hydroxyquinolines / Q000494:pharmacology*; D007502:Iron Chelating Agents / Q000494:pharmacology; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017208:Rats, Wistar; D013311:Streptozocin
chemical_list: C517687:5-(N-methyl-N-propargylaminomethyl)-8-hydroxyquinoline; D000975:Antioxidants; D006912:Hydroxyquinolines; D007502:Iron Chelating Agents; D008996:Monoamine Oxidase Inhibitors; D018696:Neuroprotective Agents; D013311:Streptozocin; D002374:Catalase