Hepato- and neurotoxicity induced by thioacetamide: protective effects of melatonin and dimethylsulfoxide.
The effects of melatonin and dimethylsulfoxide (DMSO) on liver and brain oxidative stress, hepatic failure and blood urea nitrogen (BUN) level changes produced by a single dose of thioacetamide (TAA) in Wistar rats were studies. A dose of either melatonin (3 mg kg(-1)day(-1)) or DMSO (2 g kg(-1)day(-1)) was injected for 3 days before and for 2 days after the administration of TAA (150 mg kg(-1) i.p.). Blood samples were taken from the neck vascular in order to determine ammonium, BUN and liver enzymes. We estimated lipid peroxidation products, reduced glutathione (GSH) content and catalase activity in liver and brain homogenates. TAA caused significant increases in ammonium and in the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) enzymes, while it decreased BUN values. TAA also increased lipid peroxidation product levels, but reduced GSH content and catalase activity in the liver and brain. Both melatonin and DMSO, although melatonin more significantly, decreased the intensity of the changes produced by the administration of TAA alone. Furthermore, melatonin alone or combined with TAA increased the BUN levels and decreased the ammonia values compared with control animals. These results support the antioxidative and neuro-/hepato-protective action of melatonin and a lesser action of DMSO. Likewise, these data seem to support the hypothesis of an effect of melatonin on urea synthesis.
Túnez
Isaac
I
Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Universidad de Cordoba, Avda. Menendez Pidal s/n, 14004 Cordoba, Spain.
Muñoz
M Carmen
MC
Villavicencio
Michelle A
MA
Medina
Francisco J
FJ
de Prado
Estíbaliz Pérez
EP
Espejo
Isabel
I
Barcos
Montserrat
M
Salcedo
Manuel
M
Feijóo
Montserrat
M
Montilla
Pedro
P
D000410:Alanine Transaminase / Q000097:blood; D000641:Ammonia / Q000097:blood; D000818:Animals; D001806:Blood Urea Nitrogen; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002374:Catalase / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000097:blood; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008107:Liver Diseases / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013853:Thioacetamide
D020011:Protective Agents; D013853:Thioacetamide; D000641:Ammonia; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D000410:Alanine Transaminase; D005978:Glutathione; D008550:Melatonin; D004121:Dimethyl Sulfoxide