[Ultrastructural alterations in colonic mucosa of nifurtimox treated rats].
Nifurtimox (Nfx) is a chemotherapeutic agent used in the treatment of acute Chagas' disease. Clinical and experimental studies with this nitroheterocyclic compound evidenced serious undesirable side effects. These were correlated with Nfx nitroreduction to a nitroanion radical followed by superoxide anion generation through a redox cycling process. The aim of this study was to verify whether the oral administration of Nfx to Sprague Dawley male rats (100 mg.kg-1, p.o.) produced any observable ultrastructural alteration in the cells of the colonic mucosa. Results showed that 24 h after Nfx administration there were observable alterations in this type of cells. They essentially consisted of moderate dilatation of their endoplasmic reticulum and intense dilatation of their Golgi complex. Already 1 and 3 h after Nfx administration, the original compound reached a concentration of 9.7 +/- 2.9 and 7.0 +/- 1.7 nmol.g-1 respectively in the colonic tissue. Studies on Nfx nitroreductase activity of colonic mucosa as determined spectrophotometrically and by HPLC methods showed that the microsomal fraction (from 0.72 +/- 0.29 to 0.26 +/- 0.04 nmol Nfx.min-1.mg-1 protein) but not the cytosol had the ability to nitroreduce Nfx. The results obtained show a correlation between the ultrastructural localization of injury and that of nitroreductase activity. The intense deleterious effects of Nfx in the Golgi apparatus suggest the potential occurrence of alterations in the synthesis/storage of secretory products of the colonic mucosa.
Montalto de Mecca
M
M
Centro de Investigaciones Toxicológicas (CEITOX-CITEFA-CONICET), Villa Martelli, J.B. de La Salle 4397, 1603 Villa Martelli, Provincia de Buenos Aires, Argentina.
Rodríguez de Castro
C
C
Díaz
E G
EG
Castro
J A
JA
D000818:Animals; D001711:Biotransformation; D003106:Colon / Q000187:drug effects* / Q000648:ultrastructure; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron / Q000379:methods; D009547:Nifurtimox / Q000378:metabolism / Q000494:pharmacology*; D009601:Nitroreductases / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley
D009601:Nitroreductases; D009547:Nifurtimox