RESUMO
A 2-week study in rats identified target organs of oxfendazole toxicity to be bone marrow, epididymis, liver, spleen, testis, and thymus. Female rats had greater oxfendazole exposure and exhibited toxicities at lower doses than did males. Decreased white blood cell levels, a class effect of benzimidazole anthelmintics, returned to normal during the recovery period. The no observed adverse effect level was determined to be >5 but <25 mg/kg/d and the maximum tolerated dose 100 mg/kg/d. The highest dose, 200 mg/kg/d, resulted in significant toxicity and mortality, leading to euthanization of the main study animals in this group after 7 days. Oxfendazole did not exhibit genetic toxicology signals in standard Ames bacterial, mouse lymphoma, or rat micronucleus assays nor did it provoke safety concerns when evaluated for behavioral effects in rats or cardiovascular safety effects in dogs. These results support the transition of oxfendazole to First in Human safety studies preliminary to its evaluation in human helminth diseases.
Assuntos
Anti-Helmínticos/farmacocinética , Benzimidazóis/farmacocinética , Administração Oral , Animais , Anti-Helmínticos/efeitos adversos , Anti-Helmínticos/toxicidade , Benzimidazóis/efeitos adversos , Benzimidazóis/toxicidade , Sistema Cardiovascular/efeitos dos fármacos , Cães , Relação Dose-Resposta a Droga , Feminino , Leucemia L5178/genética , Masculino , Camundongos , Testes para Micronúcleos , Testes de Mutagenicidade , Ratos , Ratos Sprague-DawleyRESUMO
Taenia solium taeniasis/cysticercosis is one of few potentially eradicable infectious diseases and is the target of control programs in several countries. The larval stage of this zoonotic cestode invades the human brain and is responsible for most cases of adult-onset epilepsy in the world. Our current understanding of the life cycle implicates humans as the only definitive host and tapeworm carrier, and thus the sole source of infective eggs that are responsible for cysticercosis in both human and pigs through oral-faecal transmission. Here we review transmission dynamics of porcine cysticercosis including an alternative pig-to-pig route of transmission, previously not suspected to exist. Second-hand transmission of T. solium eggs could explain the overdispersed pattern of porcine cysticercosis, with few pigs harbouring heavy parasite burdens and many more harbouring small numbers of parasites.