title: Benznidazole-induced ultrastructural and biochemical alterations in rat esophagus.
abstract: Benznidazole (Bz) is a drug used in the chemotherapy of the acute and intermediate phases of Chagas' disease (American Trypanosomiasis), an endemic parasitic disease afflicting more than 16 million people in Latin America. Serious toxic side effects of Bz have been reported in treated human beings and in experimental animals. Bz toxicity would be linked to its nitroreductive bioactivation to reactive intermediates and to the corresponding amine known to occur in vivo and mediated by different enzymatic systems. In the present study the presence of Bz nitroreductases in rat esophagus and the occurrence of Bz induced esophageal cell injury are described. Already 1 and 3 h after an intragastric Bz administration to Sprague-Dawley male rats (240-260 g body weight) at a dose of 100 mg/kg esophageal levels of the drug were 66.4+/-4.0 and 149.2+/-14.3 nmol per g tissue, respectively. The esophageal mucosa homogenates exhibited Bz nitroreductase activity attributable to the participation of cytochrome P450 reductase and xanthine oxidoreductase (XOR). The ultrastructural observation of esophageal tissue from Bz treated animals 24 h after its administration evidenced: detachment and conglomeration of polyribosomes, reduction in the presence of desmosomes and of the amount of bacteria on its surface. The potential significance of these alterations is not fully clear at present. However, these deleterious effects might be additive or synergistic with those induced by the evolution of the disease.
authors.affiliation: Centro de Investigaciones Toxicológicas, CEITOX-CITEFA/CONICET, J.B. de La Salle 4397, B1603ALO Villa Martelli, Provincia de Buenos Aires, Buenos Aires, Argentina. ceitox@dd.com.ar
authors.forename: Carmen R
authors.initials: CR
authors.lastname: de Castro
authors.forename: María
authors.initials: M
authors.lastname: Montalto de Mecca
authors.forename: Silvia L
authors.initials: SL
authors.lastname: Fanelli
authors.forename: Elida C
authors.initials: EC
authors.lastname: de Ferreyra
authors.forename: Edith G
authors.initials: EG
authors.lastname: Díaz
authors.forename: José A
authors.initials: JA
authors.lastname: Castro
mesh_terms: D000818:Animals; D004935:Esophageal Diseases / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006651:Histocytochemistry; D008297:Male; D008854:Microscopy, Electron; D009593:Nitroimidazoles / Q000633:toxicity*; D009601:Nitroreductases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014344:Trypanocidal Agents / Q000633:toxicity*
chemical_list: D009593:Nitroimidazoles; D014344:Trypanocidal Agents; C029492:aromatic NADH-dependent nitroreductase; D009601:Nitroreductases; C009999:benzonidazole