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

More documents

Recommendations

Info

INTRODUCTION et al. 1993), probably through formation of insoluble complexes with aluminium ion in the gut (Schaefer et al. 1988). Three mechanisms, reviewed by Greger and Sutherland (1997), were proposed to explain the increase in aluminium absorption provoked by citrate: enhanced aluminium solubility in the gastrointestinal tract, transport of aluminium citrate into mucosal cells, and opening of epithelial tight junctions that are present between mucosal cells (Taylor et al. 1998). 58 Aluminium absorption does not seem to happen in the stomach where most aluminium is converted to soluble monomolecular species at low pH (Froment et al. 1989). At near-neutral pH aluminium precipitation occurs in the intestine. Consequently, the small portion of aluminium accessible for transport is the part that has been complexed with organic molecules in the stomach, allowing it to remain soluble at higher pH of the small intestine (Reiber et al. 1995). The primary site of aluminium absorption is the proximal intestine (Greger and Sutherland 1997). The precise mechanism of gastrointestinal absorption is not yet fully known. It has been suggested that intestinal absorption of aluminium occurs paracellularly along enterocytes and through tight junctions by passives processes (Exley et al. 1996) and transcellularly through enterocytes involving passive facilitated and active transport processes, such as calcium uptake and sodium transport processes, and a role for transferrin (Greger 1993, Greger and Sutherland 1997). Interestingly, it was suggested that each aluminium species likely has its own absorption mechanism (Van der Voet 1992). Intranasal absorption Inhalation exposure to aluminium occurs from cosmetic (aerosols), environmental and occupational sources (fumes, dusts, flakes). Inhaled aluminium was suggested to accumulate in the brain through absorption via the olfactory system (Roberts 1986, Exley et al. 1996) or through systemic absorption via the lung epithelia (Gitelman et al. 1995) and through the gastrointestinal tract as particulates are swallowed (Rollin et al. 1993). Pulmonary absorption seems to be more efficient than gastrointestinal absorption. Actually, Jones and Benett (1986) estimated that
INTRODUCTION approximately 3% of aluminium is absorbed into the blood from the lung. Although there is still controversy regarding the ability of aluminium to enter the brain from nasal cavity, it has been suggested that aluminium may be able of directly entering the brain from the nose through olfactory neurons. These latter, which are the only part of the CNS with direct contact to external milieu, are located in the roof of the nasal cavity and project to the olfactory bulb. These neurons synapse with complex pathways in the olfactory bulb which subsequently project to other cerebral areas, such as the olfactory cortex, cortex, and hippocampus. A few studies tried to demonstrate that aluminium distribution in the brain occurs through olfactory nerve uptake, axonal and trans- synaptic transport. Absorption of aluminium from the olfactory pathway has been studied in rabbits exposed to aluminium lactate application in the upper nasal cavity for one month. This resulted in aluminium accumulation in the olfactory bulb, pyriform cortex, hippocampus and cerebral cortex (Perl and Good 1987) although this prolonged exposure may probably have led to mechanical disruption of the olfactory epithelia (Lewis et al. 1994). Rats exposed to aluminium acetylacetonate had aluminium deposits in the olfactory bulb, ponsmedulla and hippocampus (Zatta et al. 1993). One nose-only exposure study showed that aluminium was also distributed to the brain stem of rats using aluminium chlorohydrate (Divine et al. 1999). Dermal absorption Aluminium chloride was shown to be absorbed through the skin when applied to the skin of mice, and to accumulate in both serum and brain, especially in the hippocampus (Anane et al. 1995). Nevertheless, systemic absorption of the metal may have been enhanced by mice shaving prior to its application. As aluminium chlorhydrate is the active ingredient extensivey used in antiperspirants, the skin was predicted to be another route of aluminium entry into the systemic circulation (Exley 2004b). Aluminium chlorhydrate is thought to precipitate inside the eccrine sweat glands and to form insoluble aluminium hydroxyde, which then physically blocks the sweat duct (Quartrale 1988, Teagraden et al. 1982) but its efficacy in reducing perspiration may also be due to chemical inhibition of the sweat gland (Strassburger and 59
Page 1:
Universidade de Santiago de Compost
Page 5:
Don Ramón Soto Otero y Doña Estef
Page 9 and 10:
Acknowledgements The work of this t
Page 11 and 12:
Abbreviations AA ascorbic acid AD A
Page 13:
Abbreviations (continuation) PCC pr
Page 16 and 17:
List of figures (continuation) Chap
Page 19 and 20:
TABLE OF CONTENTS INTRODUCTION ....
Page 21:
CHAPTER 3 Brain oxidative stress an
Page 25 and 26:
INTRODUCTION PARKINSON’S DISEASE
Page 27 and 28:
INTRODUCTION PD is found in all eth
Page 29 and 30:
Bradykinesia INTRODUCTION Bradykine
Page 31 and 32: INTRODUCTION predate the occurrence
Page 33 and 34: Table 1: Differential diagnostic in
Page 35 and 36: INTRODUCTION Table 3: National Inst
Page 37 and 38: Figure 4: Dopamine catabolism (Mén
Page 39 and 40: The basal ganglia INTRODUCTION The
Page 41 and 42: The death of SNpc DAergic neurons I
Page 43 and 44: INTRODUCTION the dorsomedial part o
Page 45 and 46: INTRODUCTION characterized as are l
Page 47 and 48: INTRODUCTION (Olanow et al. 2004).
Page 49 and 50: Etiology and pathogenesis of PD INT
Page 51 and 52: Ageing INTRODUCTION Ageing remains
Page 53 and 54: INTRODUCTION The finding of MPTP to
Page 55 and 56: INTRODUCTION may clarify why many n
Page 57 and 58: Misfolding and aggregation of prote
Page 59 and 60: INTRODUCTION (E3) (Figure 18A). Los
Page 61 and 62: INTRODUCTION in connection with Par
Page 63 and 64: INTRODUCTION Oxidative damage happe
Page 65 and 66: DA metabolism as a source of ROS IN
Page 67 and 68: Contribution of oxidative and nitro
Page 69 and 70: Excitotoxicity INTRODUCTION Glutama
Page 71 and 72: INTRODUCTION al. 1996, Cicchetti et
Page 73 and 74: Experimental models of PD INTRODUCT
Page 75 and 76: INTRODUCTION induce selective DAerg
Page 77 and 78: ALUMINIUM General features INTRODUC
Page 79 and 80: INTRODUCTION Varying amounts of alu
Page 81: INTRODUCTION and antiperspirants co
Page 85 and 86: Excretion INTRODUCTION As insoluble
Page 87 and 88: INTRODUCTION 3.5 mg may be increase
Page 89 and 90: INTRODUCTION Oteiza 1999), non-iron
Page 91 and 92: Aluminium as a cell membrane menace
Page 93 and 94: INTRODUCTION mobilization of Ca 2+
Page 95: Aluminium impairs neurotransmission
Page 99 and 100: AIMS OF THE PRESENT THESIS The main
Page 101: OBJETIVOS
Page 104 and 105: OBJETIVOS 3) Evaluar de forma preci
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 154 and 155:
CHAPTER 3 Effects of aluminium admi
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
Page 199 and 200:
Publications as a direct result fro
Page 201:
REFERENCES
Page 204 and 205:
REFERENCES Agil A., Duran R., Barre
Page 206 and 207:
REFERENCES Baquet Z. C., Bickford P
Page 208 and 209:
REFERENCES 184 1,2,3,6-tetrahydropy
Page 210 and 211:
REFERENCES 186 compacta of the subs
Page 212 and 213:
REFERENCES Chung K. K., Dawson V. L
Page 214 and 215:
REFERENCES Davies K. J. (2001) Degr
Page 216 and 217:
REFERENCES Dhillon A. S., Tarbutton
Page 218 and 219:
REFERENCES Ekstrand M. I., Falkenbe
Page 220 and 221:
REFERENCES Fleming S. M., Delville
Page 222 and 223:
REFERENCES Ghribi O., Dewitt D. A.,
Page 224 and 225:
REFERENCES Good P. F., Olanow C. W.
Page 226 and 227:
REFERENCES Hamilton E. I., Miniski
Page 228 and 229:
REFERENCES Hirsch E. C., Brandel J.
Page 230 and 231:
REFERENCES Inden M., Kitamura Y., T
Page 232 and 233:
REFERENCES Johnson V. J. and Sharma
Page 234 and 235:
REFERENCES Kim W. G., Mohney R. P.,
Page 236 and 237:
REFERENCES Kuhn W., Winkel R., Woit
Page 238 and 239:
REFERENCES 214 K.D. and Polymeropou
Page 240 and 241:
REFERENCES Maraganore D. M., Lesnic
Page 242 and 243:
REFERENCES McCord J. M. and Fridovi
Page 244 and 245:
REFERENCES Miu A. C. and Benga O. (
Page 246 and 247:
REFERENCES Nair V. D., McNaught K.,
Page 248 and 249:
REFERENCES Onyango I. G. (2008) Mit
Page 250 and 251:
REFERENCES Perez F. A. and Palmiter
Page 252 and 253:
REFERENCES Przedborski S. and Goldm
Page 254 and 255:
REFERENCES Rifat S. L., Eastwood M.
Page 256 and 257:
REFERENCES Rymar V. V., Sasseville
Page 258 and 259:
REFERENCES Savory J., Herman M. M.
Page 260 and 261:
REFERENCES Shimizu H., Mori T., Koy
Page 262 and 263:
REFERENCES 238 the generation of hy
Page 264 and 265:
REFERENCES Taylor G. A., Moore P. B
Page 266 and 267:
REFERENCES Um J. W., Stichel-Gunkel
Page 268 and 269:
REFERENCES Vila M. and Przedborski
Page 270 and 271:
REFERENCES Whitehead M. W., Farrar
Page 272 and 273:
REFERENCES Yokel R. A. (2002a) Alum
Page 274:
REFERENCES Zhou W., Zhu M., Wilson
show all

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

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?