Mechanisms of aluminium neurotoxicity in oxidative stress-induced ...
Mechanisms of aluminium neurotoxicity in oxidative stress-induced ...
Mechanisms of aluminium neurotoxicity in oxidative stress-induced ...
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Intranasal absorption ........................................................................................................................................................... 58<br />
Dermal absorption ............................................................................................................................................................... 59<br />
Distribution <strong>of</strong> <strong>alum<strong>in</strong>ium</strong> <strong>in</strong> the body ................................................................................................................................. 60<br />
Excretion .............................................................................................................................................................................. 61<br />
Elim<strong>in</strong>ation rate ................................................................................................................................................................... 61<br />
Alum<strong>in</strong>ium <strong>in</strong>flux and efflux <strong>in</strong>to the bra<strong>in</strong> ........................................................................................... 62<br />
Putative mechanisms <strong>of</strong> <strong>alum<strong>in</strong>ium</strong> <strong>neurotoxicity</strong> ................................................................................ 63<br />
Alum<strong>in</strong>ium and <strong>oxidative</strong> <strong>stress</strong> ........................................................................................................................................... 64<br />
The bra<strong>in</strong>: a target for <strong>alum<strong>in</strong>ium</strong> ................................................................................................................................. 64<br />
Alum<strong>in</strong>ium catalyses iron-driven biological oxidations ................................................................................................. 65<br />
Alum<strong>in</strong>ium stimulates superoxide-/non-iron-driven biological oxidations ................................................................... 65<br />
Alum<strong>in</strong>ium-superoxide complex theory ........................................................................................................................ 66<br />
Alum<strong>in</strong>ium <strong>in</strong>hibits the antioxidant enzymes and others .............................................................................................. 66<br />
Alum<strong>in</strong>ium as a cell membrane menace .............................................................................................................................. 67<br />
Alum<strong>in</strong>ium affects cell signal<strong>in</strong>g ........................................................................................................................................... 68<br />
AIMS OF THE PRESENT THESIS ............................................................... 75<br />
OBJETIVOS DE LA PRESENTE TESIS ......................................................... 79<br />
CHAPTER 1 Time-course <strong>of</strong> bra<strong>in</strong> <strong>oxidative</strong> damage caused<br />
by <strong>in</strong>trastriatal adm<strong>in</strong>istration <strong>of</strong> 6-hydroxydopam<strong>in</strong>e <strong>in</strong> a rat<br />
model <strong>of</strong> Park<strong>in</strong>son’s disease ................................................................ 83<br />
ABSTRACT ....................................................................................................................... 85<br />
INTRODUCTION .............................................................................................................. 86<br />
MATERIALS AND METHODS ............................................................................................ 88<br />
Chemicals .............................................................................................................................................. 88<br />
Animal treatment.................................................................................................................................. 88<br />
Bra<strong>in</strong> samples ........................................................................................................................................ 89<br />
Determ<strong>in</strong>ation <strong>of</strong> TBARS ....................................................................................................................... 89<br />
Determ<strong>in</strong>ation <strong>of</strong> prote<strong>in</strong> carbonyl content (PCC) ................................................................................. 89<br />
Determ<strong>in</strong>ation <strong>of</strong> prote<strong>in</strong> thiol content (PTC) ....................................................................................... 90<br />
Statistical analysis ................................................................................................................................. 91<br />
RESULTS .......................................................................................................................... 92<br />
Effects <strong>of</strong> 6-OHDA adm<strong>in</strong>istration on TBARS concentration ................................................................. 92<br />
Effects <strong>of</strong> 6-OHDA adm<strong>in</strong>istration on PCC ............................................................................................. 92<br />
Effects <strong>of</strong> 6-OHDA adm<strong>in</strong>istration on PTC ............................................................................................. 93<br />
DISCUSSION .................................................................................................................... 94<br />
CHAPTER 2 Analysis <strong>of</strong> bra<strong>in</strong> regional distribution <strong>of</strong><br />
<strong>alum<strong>in</strong>ium</strong> <strong>in</strong> rats via oral and <strong>in</strong>traperitoneal adm<strong>in</strong>istration ............. 103<br />
ABSTRACT ..................................................................................................................... 105<br />
INTRODUCTION ............................................................................................................ 106<br />
MATERIALS AND METHODS .......................................................................................... 107<br />
Chemicals ............................................................................................................................................ 107<br />
Animal treatment................................................................................................................................ 107<br />
Bra<strong>in</strong> samples ...................................................................................................................................... 108<br />
Electrothermal atomic absorption spectrometry (ETAAS) .................................................................. 108<br />
Statistical analysis ............................................................................................................................... 109<br />
RESULTS ........................................................................................................................ 110<br />
Alum<strong>in</strong>ium distribution <strong>in</strong> the bra<strong>in</strong> after oral and i.p. adm<strong>in</strong>istration ............................................... 110<br />
DISCUSSION .................................................................................................................. 111