title: Reduced brain antioxidant capacity in rat models of betacytotoxic-induced experimental sporadic Alzheimer's disease and diabetes mellitus.
abstract: It is believed that oxidative stress (OS) plays a central role in the pathogenesis of metabolic diseases like diabetes mellitus (DM) and its complications (like peripheral neuropathy) as well as in neurodegenerative disorders like sporadic Alzheimer's disease (sAD). Representative experimental models of these diseases are streptozotocin (STZ)-induced diabetic rats and STZ-intracerebroventricularly (STZ-icv) treated rats, in which antioxidant capacity (AC) against peroxyl (ORAC(-ROO) (*)) and hydroxyl (ORAC(-OH) (*)) free radicals (FR) was measured in three different brain regions: the hippocampus (HPC), the cerebellum (CB), and the brain stem (BS) by means of oxygen radical absorbance capacity (ORAC) assay. In the brain of both STZ-induced diabetic and STZ-icv treated rats decreased AC has been found demonstrating regionally specific distribution. In the diabetic rats these abnormalities were not associated with the development of peripheral diabetic neuropathy (PDN). Also, these abnormalities were not prevented by the intracerebroventricularly (icv) pretreatment of glucose transport inhibitor 5-thio-D: -glucose (TG) in the STZ-icv treated rats, suggesting different mechanism of STZ-induced central effects from those at the periphery. Similarities of the OS alterations in the brain of STZ-icv rats and humans with sAD could be useful in the search for the new drugs in the treatment of sAD that have antioxidant activity. In the STZ-induced diabetic animals the existence of PDN was tested by the paw pressure test, 3 weeks following the diabetes induction. Mechanical nociceptive thresholds were measured three times at 10-min intervals by applying increased pressure to the hind paw until the paw-withdrawal or overt struggling was elicited. Only those diabetic animals which demonstrated decreased withdrawal threshold values in comparison with the control non-diabetic animals (C) were considered to have developed the PDN.
authors.affiliation: Department of Chemistry, Faculty of Science, University of Sarajevo, Zmaja od Bosne 35, 71 000, Sarajevo, Bosnia and Herzegovina
authors.forename: Ismet
authors.initials: I
authors.lastname: Tahirovic
authors.forename: Emin
authors.initials: E
authors.lastname: Sofic
authors.forename: Aida
authors.initials: A
authors.lastname: Sapcanin
authors.forename: Ismet
authors.initials: I
authors.lastname: Gavrankapetanovic
authors.forename: Lidija
authors.initials: L
authors.lastname: Bach-Rojecky
authors.forename: Melita
authors.initials: M
authors.lastname: Salkovic-Petrisic
authors.forename: Zdravko
authors.initials: Z
authors.lastname: Lackovic
authors.forename: Siegfried
authors.initials: S
authors.lastname: Hoyer
authors.forename: Peter
authors.initials: P
authors.lastname: Riederer
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced* / Q000378:metabolism*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000975:Antioxidants / Q000378:metabolism*; D001923:Brain Chemistry / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced* / Q000378:metabolism; D003929:Diabetic Neuropathies / Q000378:metabolism / Q000473:pathology; D005609:Free Radicals / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism; D007276:Injections, Intraventricular; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D010147:Pain Measurement / Q000187:drug effects; D010545:Peroxides / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013311:Streptozocin / Q000008:administration & dosage
chemical_list: D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D005609:Free Radicals; D009419:Nerve Tissue Proteins; D010545:Peroxides; D017382:Reactive Oxygen Species; D017665:Hydroxyl Radical; D013311:Streptozocin