Aluminum accumulation and neurotoxicity in Swiss-Webster mice after long-term dietary exposure to aluminum and citrate.
The present study was performed to determine aluminum uptake, retention, and neurotoxic effects in the presence of dietary citrate. Six-week-old female Swiss-Webster mice were fed semipurified diets containing 3.5% sodium citrate and either 3 micrograms Al/g diet (3 Al) or 1,000 micrograms Al/g diet (1,000 Al) as AlCl3. After 5 to 7 weeks of feeding these diets, changes in behavior were assessed using the National Institute of Environmental Health Sciences Neurobehavioral Test Battery. Liver and bone Al concentrations in the 1,000 Al group were higher than in the 3 Al group at both the 5- and 7-week time points. Spinal cord Al concentrations in the 1,000 Al group were 200% higher at 5 weeks (P < .01) than in controls, and brain nuclear fraction Al concentrations in the 1,000 Al group were 150% higher at 5 and 7 weeks (P < .01) than in the 3 Al group. The Neurobehavioral Test Battery showed lower grip strength and greater startle responsiveness in the 1,000 Al group compared with the 3 Al group at both the 5- and 7-week time points. Based on reports that Al can act as a pro-oxidant, we examined Al-induced brain lipid and protein oxidative damage; neither was evident in the Al-intoxicated mice. In summary, feeding of Al and citrate to mice resulted in Al accumulation in the central nervous system, and this accumulation was associated with overt signs of neurotoxicity. Brain protein and lipid oxidative damage was not associated with early manifestation of Al toxicity.
Oteiza
P I
PI
Instituto de Quimica y Fisicoquimica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquimica, Universidad de Buenos Aires, Argentina.
Keen
C L
CL
Han
B
B
Golub
M S
MS
D000535:Aluminum / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001842:Bone and Bones / Q000737:chemistry / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry; D002951:Citrates / Q000008:administration & dosage*; D019343:Citric Acid; D004032:Diet; D004305:Dose-Response Relationship, Drug; D005260:Female; D050356:Lipid Metabolism; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D009420:Nervous System / Q000187:drug effects*; D009424:Nervous System Physiological Phenomena; D010084:Oxidation-Reduction; D011506:Proteins / Q000378:metabolism; D013116:Spinal Cord / Q000737:chemistry / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis / Q000378:metabolism; D013997:Time Factors
D002951:Citrates; D011506:Proteins; D017392:Thiobarbituric Acid Reactive Substances; D019343:Citric Acid; D000535:Aluminum