Brain catalase in the streptozotocin-rat model of sporadic Alzheimer's disease treated with the iron chelator-monoamine oxidase inhibitor, M30.

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.

Antioxidant capacity in rat brain after intracerebroventricular treatment with streptozotocin and alloxan--a preliminary study.

Intracerebroventricular (icv) administration of betacytotoxic drug streptozotocin (STZ) produces long-term and progressive cognitive deficits in rats, as well as deficits in cerebral glucose and energy metabolism. These changes resemble those found in the brain of patients with sporadic Alzheimer's disease (sAD), and therefore, STZ-icv treated rats have been proposed as an experimental model of sAD. In this study the antioxidant capacity (AC), using manual oxygen radical absorbance capacity (ORAC) assay, was measured in the rat brain frontoparietal cortex (FC) and brainstem-cerebellum region (BS-CB) after administration of STZ and another betacytotoxic drug alloxan (AL). Region-specific differences of AC were found, which were more expressed when hydroxyl radical (ORAC(-OHo)) generator was used in the assay. AC against ORAC(-OHo) was significantly lower in BS-CB than in FC of the control rats. Furthermore, ORAC(-OHo) significantly decreased in BS-CB 3-months following the icv administration of AL, but significantly increased following the TG+AL combined treatment in comparison with the controls. However, 3-months following the icv treatment of AL combination with a different glucose transport inhbitor, 3-O-methyl-D-glucose, ORAC(-OHo) values in BS-CB and ORAC(-ROOo) values in FC were significantly decreased in comparison to the controls. Our results suggest that betacytotoxic-icv treatment alters antioxidant defense systems in the brain, which particularly regarding the STZ-icv treatment, could be a useful tool in search for possible new antioxidant treatments of the neurodegenerative disorders such as sAD.

Brain antioxidant capacity in rat models of betacytotoxic-induced experimental sporadic Alzheimer's disease and diabetes mellitus.

It is believed that oxidative stress 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 against peroxyl (ORAC(-ROO)*) and hydroxyl (ORAC(-OH)*) free radical was measured in three different brain regions (hippocampus, cerebellum, and brain stem) by means of oxygen radical absorbance capacity (ORAC) assay. In the brain of both STZ-induced diabetic and STZ-icv treated rats decreased antioxidant capacity has been found demonstrating regionally specific distribution. In the diabetic rats these abnormalities were not associated with the development of peripheral diabetic neuropathy. Also, these abnormalities were not prevented by the icv pretreatment of glucose transport inhibitor 5-thio-D-glucose in the STZ-icv treated rats, suggesting different mechanism for STZ-induced central effects from those at the periphery. Similarities in the oxidative stress alterations in the brain of STZ-icv rats and humans with sAD could be useful in the search for new drugs in the treatment of sAD that have antioxidant activity.

Antioxidant capacity in postmortem brain tissues of Parkinson's and Alzheimer's diseases.

Oxidative stress has been associated with damage and progressive cell death that occurs in neurodegenerative disorders such as Parkinson's disease (PD) and Alzheimer's disease (AD). The aim of this study was to investigate the antioxidant capacity in postmortem motor cortex (MC), nucleus caudatus (NC), gyrus temporalis (GT) and substantia nigra (SN) from controls (C) and patients with PD and AD. The initial samples consisted of 68 subjects of PD, AD and C. Brains were matched for age, sex and postmortem time. Brain tissue was homogenized in a phosphate buffer pH 7.3 and separated with two-step centrifugation at 15,000rpm for 30 min and 15,000 rpm for 10 min at 4 degrees C. Antioxidant capacity in the supernatants was measured using the oxygen radical absorbance assay (ORAC). The results showed that in the SN of parkinsonian's brain the balance between production of free radicals and the neutralization by a complex antioxidant system is disturbed. No changes in the antioxidant capacity of postmortem MC and NC of parkinsonian's brain in comparison with C were found. In the SN of parkinsonian's brain, antioxidant capacity seems to be lower in comparison with C (p < 0.05). Antioxidant capacity against peroxyl radical showed that MC of AD patients was lower than in the MC of C (p < 0.005). In NC of AD patients the antioxidant capacity against hydroxyl radical was increased in comparison with C (p < 0.04). No changes in the antioxidant capacity were found in brain tissues of AD in comparison with C, when CuSO4 was used as a free radical generator.

Antioxidant capacity of the neurohormone melatonin.

The aim of this study was to elucidate the antioxidant behaviour of melatonin (M) and determine its activity-structure relationship. M or 5-metoxy-N acetyltriptamine is a neurohormone secreted by the pineal gland, which plays a proven role in maintaining sleep-wake rhythms. The antioxidant capacity of M was analysed using the oxygen radical absorbance capacity (ORAC) assay. Furthermore, spectral measurements for aerobic photolytic reaction of neutral red (NR) and degree of inhibition of photolysis with M, glutathione (GSH), ascorbic acid (AA) and vitamin E analogue Trolox were studied at room temperature 25 degrees C, using visible (VIS) and ultra-violet (UV) radiations. In the ORAC assay 2,2-azobis (2-amidino-propane)dihydrochloride (AAPH) a peroxyl radical generator, ROO degrees ; H2O2-Cu2+, mainly a hydroxyl radical generator, degrees OH; and Cu2+ a transition metal were used. Although some studies indicated that M is a powerful antioxidant, no one has compared its antioxidant capacities with GSH, E-vitamin and AA, using three free radical (FR) generators in an assay which utilizes an area-under curve technique and thus combines both inhibition time and inhibition degree of FR action by an antioxidant into a single quantity. In the current study, we used ORAC assay with three FR generators. The assay is based on propensity of the fluorescence emitted by the protein beta-phycoerythrin (beta-PE) from porphyridium cruentum to be quenched when exposed to FR action. M in our experiments acted as a universal antioxidant against ROO degrees and degrees OH radicals. Also, M served as an antioxidant in the presence of Cu2+. M, which is a lipid-soluble compound, was a twice more powerful antioxidant than vitamin E, and four times than AA or GSH. Furthermore, M inhibited aerobic photolysis of NR photoinduced with VIS and UV rays faster and more effectively, than AA, GSH or vitamin E. AA with NR, under aerobic conditions during irradiation with VIS and UV acted as a pro-oxidant. M may be the premier molecule to protect the cells from oxidative stress.