Aluminum-induced neurotoxicity and oxidative damage in rabbits: protective effect of melatonin.
OBJECTIVE
The present study was aimed to investigate: (1) the neurotoxic oxidative damage of orally administered aluminum chloride (AlCl3) in rabbits (Biochemical and morphopathological studies). (2) The effect of melatonin as an antioxidant and free radical scavenger on oxidative neuropathic changes.


METHODS
Thirty-five male rabbits were divided into 4 groups (A, B, C [10 animals each] and D [5 animals]). Group A received AlCl3 (20 mg/l via drinking water for 3 months). Group B received AlCl3 for 3 months then administered with melatonin (10 mg/kg b.w. sc daily for 15 days). Group C received AlCl3 plus melatonin for 3 months. Group D received the solvent and served as control. Malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA) as lipid peroxides as well as superoxide dismutase (SOD) as an antioxidant enzyme were measured. Aluminum residue in the brain tissue was measured spectrophotometerically. The morphopathological changes were also examined by light and electron microscopes.


RESULTS
MDA and 4-HAD were significantly increased in group A versus those of controls while significantly decreased in groups B and C compared with those of A group. SOD run in an opposite manner. Aluminum concentration was significantly increased in groups A, B and C when compared with group D while it significantly decreased in groups B and C when compared with that of group A. The neuropathlogical examination in the animals of group A revealed atrophy and apoptosis of the neurons in cerebral cortex and hippocampus. This was associated with neurofibrillary degeneration as well as argyrophilic inclusion. Schwan cell degeneration and nerve fiber demylination were also encountered. The elaboration of lipid peroxidation products, inhibition of antioxidant enzymes and the morphopathological changes were minimized in the Al/Mel treated groups and markedly improved in Al+Mel treated group


CONCLUSIONS
Chronic aluminum exposure in rabbits had dramatic encephalopathic morphopathological lesions. It enhances the lipid peroxidation production and inhibits the SOD enzyme. Melatonin had a good prophylactic effect as an antioxidant in aluminum encephalopathy.
Abd-Elghaffar
Sary Kh
SKh
Department of Pathology and Clinical Pathology, Faculty of Science, Assiut University, Egypt.
El-Sokkary
Gamal H
GH
Sharkawy
Ahmed A
AA
D000535:Aluminum / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008550:Melatonin / Q000627:therapeutic use*; D009410:Nerve Degeneration / Q000473:pathology / Q000517:prevention & control; D009454:Neurofibrils / Q000473:pathology; D018696:Neuroprotective Agents; D020258:Neurotoxicity Syndromes / Q000503:physiopathology / Q000517:prevention & control*; D018384:Oxidative Stress / Q000187:drug effects; D011817:Rabbits; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D018696:Neuroprotective Agents; D008315:Malondialdehyde; D000535:Aluminum; D013482:Superoxide Dismutase; D008550:Melatonin