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Oral toxicology studies with lapachol

1970; Elsevier BV; Volume: 17; Issue: 1 Linguagem: Inglês

10.1016/0041-008x(70)90126-2

1096-0333

Robert Morrison, Desmond Brown, J. J. Oleson, David A. Cooney,

Multicomponent Synthesis of Heterocycles

The toxic effects of orally administered lapachol were studied in rodents, dogs, and monkeys. The single dose, combined sex, oral LD50 was 0.621 g/kg in BALBc mice and greater than 2.4 g/kg in albino rats. The male and female mice LD50 values were 0.487 and 0.792 g/kg, respectively. Beagle dogs were given daily oral doses of 0.25, 0.50, 1.0 or 2.0 g/kg 6 days a week for a total of 24 doses without lethal effect. Cynomolgus monkeys were treated on the same schedule and received doses of 0.0625, 0.125, 0.25, 0.5, or 1.0 g/kg/day. Death occurred in monkeys after six doses of 0.5 g/kg/day and after five doses of 1.0 g/kg/day. Signs of toxicosis in both dogs and monkeys included moderate to severe anemia, reticulocytosis, normoblastosis, pallor of mucous membranes, bilirubinuria, and proteinuria. Additionally, transient thrombocytosis and leukocytosis, and elevated serum alkaline phosphatase activity and prothrombin times occurred in dogs. Leukopenia, thrombocytopenia, and azotemia were noted only in monkeys. The anemia was most pronounced during the first 2 weeks of treatment, and despite continued treatment, recovery was well underway in most animals by the end of the treatment period. Histopathology findings were limited to deposition of iron pigment in livers of dogs.