RESUMO
Background & objectives: Aluminum (Al) toxicity is closely linked to the pathogenesis of Alzheimer’s disease (AD). This experimental study was aimed to investigate the active avoidance behaviour of rats after intrahippocampal injection of Al, and biochemical and immunohistochemical changes in three bilateral brain structures namely, forebrain cortex (FBCx), hippocampus and basal forebrain (BF). Methods: Seven days after intra-hippocampal (CA1 sector) injection of AlCl3 into adult male Wistar rats they were subjected to two-way active avoidance (AA) tests over five consecutive days. Control rats were treated with 0.9% w/v saline. The animals were decapitated on the day 12 post-injection. The activities of acetylcholinesterase (AChE) and glucose-6-phosphate dehydrogenase (G6PDH) were measured in the FBCx, hippocampus and BF. Immunohistochemical staining was performed for transferrin receptors, amyloid β and tau protein. Results: The activities of both AChE and G6PDH were found to be decreased bilaterally in the FBCx, hippocampus and basal forebrain compared to those of control rats. The number of correct AA responses was reduced by AlCl3 treatment. G6PDH administered prior to AlCl3 resulted in a reversal of the effects of AlCl3 on both biochemical and behavioural parameters. Strong immunohistochemical staining of transferrin receptors was found bilaterally in the FBCx and the hippocampus in all three study groups. In addition, very strong amyloid β staining was detected bilaterally in all structures in AlCl3-treated rats but was moderate in G6PDH/AlCl3-treated rats. Strong tau staining was noted bilaterally in AlCl3-treated rats. In contrast, tau staining was only moderate in G6PDH/AlCl3-treated rats. Interpretation & conclusions: Our findings indicated that the G6PDH alleviated the signs of behavioural and biochemical effects of AlCl3-treatment suggesting its involvement in the pathogenesis of Al neurotoxicity and its potential therapeutic benefit. The present model could serve as a useful tool in AD investigations.
RESUMO
Ionizing radiation in differentiated thyroid cancer (DTC) patients treated with radioiodine (131-I) produces reactive oxygen species (ROS), which could induce oxidative stress with disturbance of redox balance. The aim of this study was to evaluate oxidative stress in DTC patients treated with 3.7 or 5.5 GBq of 131-I using values for serum malondialdehyde (MDA, a marker of oxidative stress), uric acid (to determine antioxidant status) and total antioxidative status (TAS). The study population included 20 DTC patients and 20 healthy controls. Significant differences in MDA concentrations were found between DTC patients before 131-I therapy and control subjects (p = 0.001), while TAS values were similar in both populations (p>0.05). There was a negative correlation between MDA concentrations and TAS in the DTC group before therapy (R2 = 0.2973, p = 0.013). Three days after 131-I therapy, MDA concentrations were higher than the pretreatment values (3.36 ± 1.69 nmol/mL vs. 2.93 ± 1.31 nmol/mL; p = 0.006), while serum uric acid concentrations declined progressively from 341.0 ± 80.39 μmol/L to 304.25 ± 77.25 μmol/L (p = 0.026) in 3 days and 291.2 ± 88.86 μmol/L (p = 0.009) in 7 days after 131-I therapy. There was no dose-dependent effect on MDA, or uric acid concentrations and TAS. Thus, 131-I therapy in DTC patients induced oxidative stress, which was accompanied by a simultaneous and extended reduction in uric acid concentration, but without significant disturbances in TAS. This is the first study that evaluated TAS capacity in DTC patients before and 7 days after 131-I therapy. The relatively stabile TAS values in these patients indicated a good protection from oxidative stress induced by high doses of ionizing radiation.