Mechanisms of aluminium neurotoxicity in oxidative stress-induced ...

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CHAPTER 3 Effects of aluminium administration on brain lipid peroxidation and protein oxidation in 6-OHDA-lesioned rats and controls 130 Once again, the concentration of TBARS was used as an index of lipid peroxidation in striatum and ventral midbrain (Fig. 5A). Both regions of animals i.p. injected with aluminium alone (subgroup D) showed a statistical difference in TBARS production compared to non-lesioned (subgroup C) control rats (+40% in ventral midbrain and +16% in striatum). Intraventricular injection of 6-OHDA resulted in a significant increase in TBARS concentration in both striatum and ventral midbrain when compared to control rats (+29% and +76%, respectively) and to animals treated with aluminium (+12% and +26%, respectively)). Ventral midbrain and striatum TBARS levels in rats i.p. treated with aluminium and intraventricularly injected with 6- OHDA were +107% and +40% (respectively) increased in respect to control animals. When compared to rats only treated with aluminium (i.e. without 6-OHDA; subgroup D), the TBARS levels of subgroup-F rats were markedly increased in both regions (+47% in ventral midbrain and +21% in striatum) and there were also significant differences when compared with subgroup E, rats only lesioned with 6-OHDA (+17% in ventral midbrain and +8% in striatum). Protein oxidation was assessed by the determination of PCC and PTC in the samples of striatum and ventral midbrain. No significant changes were noticed in the PTC (Fig. 5C) except for rats lesioned with 6- OHDA when compared with animals treated only with aluminium (–11%). By contrast, as shown in Fig. 5B, intraventricular injection of 6-OHDA induced a significant increase in the PCC in striatum and ventral midbrain (+33% and +22%, respectively) as compared with control rats. Treatment with aluminium (subgroups D) revealed a significant difference in ventral midbrain and striatum as compared to control rats (+11% and +18%, respectively). On the other hand, in subgroup F (animals treated with aluminium and lesioned with 6-OHDA) the PCC was reduced in both regions (–16% in ventral midbrain and striatum) as compared to the rats lesioned with 6-OHDA.
CHAPTER 3 In vitro effects of aluminium on the lipid peroxidation and protein oxidation induced by 6-OHDA autoxidation in brain mitochondrial preparations As depicted in Fig. 6A, the incubation of 6-OHDA (10 �M) with brain mitochondria at 37°C for 20 min induced a significant production of TBARS when compared to the mitochondria (Mit) and Mit+Al controls (+91% and +116%, respectively). Significant changes in TBARS production (+100%, +127%) were observed when the autoxidation of 6-OHDA occurred in the presence of Al 3+ (5 �M) as compared to the Mit and Mit+Al controls, respectively. However, the presence of aluminium did not significantly affect the level of TBARS found after the incubation of 6-OHDA in mitochondrial preparations when compared to the Mit+6-OHDA control. The incubation of 6-OHDA (10 �M) with brain mitochondria at 37°C for 20 min induced a significant increase in the PCC (+7%; Fig. 6B) as compared to the Mit control. However, the results obtained in the presence of Al 3+ (5 �M) were not significantly different from control values. As can be seen in Fig. 6C, the PTC exhibited a significant reduction (–9%) in the incubation of 6-OHDA (10 �M) with brain mitochondria at 37°C for 20 min when compared with that obtained in the control with mitochondria alone and Mit+Al 3 . The presence of aluminium had no significant effect on the PTC found with mitochondrial incubations when compared to controls. In vitro effects of aluminium on the enzyme activities of GPx, SOD, CAT, and MAO The results regarding the effect of aluminium on the in vitro activities of GPx, CAT, SOD, MAO-A and MAO-B enzymes are displayed in Table 1. In all cases, no significant differences were detected between assays performed in the presence and in the absence of Al 3+ (10, 50, 100 �M) 131
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Universidade de Santiago de Compost
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Don Ramón Soto Otero y Doña Estef
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Acknowledgements The work of this t
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Abbreviations AA ascorbic acid AD A
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Abbreviations (continuation) PCC pr
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List of figures (continuation) Chap
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TABLE OF CONTENTS INTRODUCTION ....
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CHAPTER 3 Brain oxidative stress an
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INTRODUCTION PARKINSON’S DISEASE
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INTRODUCTION PD is found in all eth
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Bradykinesia INTRODUCTION Bradykine
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INTRODUCTION predate the occurrence
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Table 1: Differential diagnostic in
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INTRODUCTION Table 3: National Inst
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Figure 4: Dopamine catabolism (Mén
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The basal ganglia INTRODUCTION The
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The death of SNpc DAergic neurons I
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INTRODUCTION the dorsomedial part o
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INTRODUCTION characterized as are l
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INTRODUCTION (Olanow et al. 2004).
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Etiology and pathogenesis of PD INT
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Ageing INTRODUCTION Ageing remains
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INTRODUCTION The finding of MPTP to
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INTRODUCTION may clarify why many n
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Misfolding and aggregation of prote
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INTRODUCTION (E3) (Figure 18A). Los
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INTRODUCTION in connection with Par
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INTRODUCTION Oxidative damage happe
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DA metabolism as a source of ROS IN
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Contribution of oxidative and nitro
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Excitotoxicity INTRODUCTION Glutama
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INTRODUCTION al. 1996, Cicchetti et
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Experimental models of PD INTRODUCT
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INTRODUCTION induce selective DAerg
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ALUMINIUM General features INTRODUC
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INTRODUCTION Varying amounts of alu
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INTRODUCTION and antiperspirants co
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INTRODUCTION approximately 3% of al
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Excretion INTRODUCTION As insoluble
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INTRODUCTION 3.5 mg may be increase
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INTRODUCTION Oteiza 1999), non-iron
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Aluminium as a cell membrane menace
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INTRODUCTION mobilization of Ca 2+
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Aluminium impairs neurotransmission
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AIMS OF THE PRESENT THESIS The main
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OBJETIVOS
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Page 107: CHAPTER 1 Time-course of brain oxid
Page 110 and 111: CHAPTER 1 INTRODUCTION 86 6-OHDA (2
Page 112 and 113: CHAPTER 1 MATERIALS AND METHODS Che
Page 114 and 115: CHAPTER 1 followed by centrifugatio
Page 116 and 117: CHAPTER 1 RESULTS Effects of 6-OHDA
Page 118 and 119: CHAPTER 1 DISCUSSION 94 As shown by
Page 120 and 121: CHAPTER 1 strategies or to study th
Page 122 and 123: CHAPTER 1 Fig. 2 Changes in PCC in
Page 125: CHAPTER 2
Page 129 and 130: ABSTRACT CHAPTER 2 In the present w
Page 131 and 132: MATERIALS AND METHODS Chemicals CHA
Page 133 and 134: CHAPTER 2 atomization used were 1,5
Page 135 and 136: DISCUSSION CHAPTER 2 Aluminium ente
Page 137: Table 1. Graphite furnace programme
Page 141: CHAPTER 3 Brain oxidative stress an
Page 144 and 145: CHAPTER 3 INTRODUCTION 120 The huma
Page 146 and 147: CHAPTER 3 MATERIALS AND METHODS Che
Page 148 and 149: CHAPTER 3 1:15 for hippocampus and
Page 150 and 151: CHAPTER 3 initially incorporated to
Page 152 and 153: CHAPTER 3 RESULTS In vivo effects o
Page 156 and 157: CHAPTER 3 DISCUSSION 132 Aluminium
Page 158 and 159: CHAPTER 3 hippocampus, showed simil
Page 160 and 161: CHAPTER 3 assume that the distinct
Page 162 and 163: CHAPTER 3 Fig. 1 Levels of TBARS (A
Page 164 and 165: CHAPTER 3 Fig. 2 Enzyme activity of
Page 166 and 167: CHAPTER 3 Fig. 3 Microphotographs s
Page 168 and 169: CHAPTER 3 Fig. 5 Levels of TBARS (A
Page 170 and 171: CHAPTER 3 Fig. 6 In vitro effects o
Page 173: SUMMARY
Page 176 and 177: SUMMARY values were attained at 48
Page 178 and 179: SUMMARY neurodegeneration in the DA
Page 181 and 182: CONCLUSIONS The results obtained in
Page 183: 13) Aluminium does affect neither M
Page 187 and 188: RESUMEN RESUMEN Desde el punto de v
Page 189 and 190: RESUMEN zonas cerebrales excepto en
Page 191: CONCLUSIONES
Page 194 and 195: CONCLUSIONES Capítulo 2 4) La admi
Page 196 and 197: CONCLUSIONES 172 En base a las conc
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