title: Neurohepatic toxicity of subacute manganese chloride exposure and potential chemoprotective effects of lycopene.
abstract: Excess manganese (Mn) is potentially toxic resulting in a permanent neurodegenerative disorder, clinically known as "manganism" that is distinctive for hepaticencephalopathy. The present study was designed to explore the toxic impacts of subacute Mn exposure on brain and liver tissues, and the relative abilities of lycopene in averting such neurohepatic damage. Rats were daily injected with MnCl(2) (0 or 6mg/kg, i.p.) 20 days after lycopene administration (0 or 10mg/kg, p.o.), and killed 4 weeks after MnCl(2) exposure. MnCl(2)-induced lipid peroxidation and perturbation in antioxidant system, increase of acetylcholinesterase, aminotransferases, and decrease alkaline phosphatase, and lactate dehydrogenase activities with hyperglycemia as demonstrated by Alzheimer type II astrocytosis, and periportal hepatic necrosis and apoptosis were prevented by lycopene. However, lycopene did not prevent the increased body burden of Mn and the altered Fe and Cu homeostasis induced by MnCl(2). Glutathione S-transferase and catalase activities, and glutathione content were reduced in MnCl(2)-challenged rats, and sustained by lycopene. Our results indicate that although lycopene failed to reduce Mn concentration or retain disturbed elemental status; it appears to be a highly effective in alleviating its neurohepatic deleterious effects by preventing lipid peroxidation, hyperglycemia and changes in the activity of acetylcholinesterase and hepatobiliary enzymes, and antioxidant pathways.
authors.affiliation: Department of Biochemistry, Faculty of Veterinary Medicine, Alexandria University, Egypt.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Lebda
authors.forename: Mahmoud S
authors.initials: MS
authors.lastname: El-Neweshy
authors.forename: Yasser S
authors.initials: YS
authors.lastname: El-Sayed
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002338:Carotenoids / Q000008:administration & dosage*; D002374:Catalase / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000150:complications / Q000209:etiology* / Q000517:prevention & control*; D002712:Chlorides / Q000097:blood / Q000633:toxicity*; D004195:Disease Models, Animal; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D007279:Injections, Subcutaneous / Q000379:methods; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000378:metabolism / Q000473:pathology; D000077276:Lycopene; D008297:Male; D017895:Manganese Compounds / Q000097:blood; D020258:Neurotoxicity Syndromes / Q000097:blood / Q000150:complications / Q000209:etiology* / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014131:Trace Elements / Q000097:blood; D000637:Transaminases / Q000378:metabolism
chemical_list: D000975:Antioxidants; D002712:Chlorides; D017895:Manganese Compounds; D017392:Thiobarbituric Acid Reactive Substances; D014131:Trace Elements; D002338:Carotenoids; D002374:Catalase; D005982:Glutathione Transferase; D000637:Transaminases; D000110:Acetylcholinesterase; D000469:Alkaline Phosphatase; D005978:Glutathione; C025340:manganese chloride; D000077276:Lycopene