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 nitroheterocy clic compound evidenced serious undesirable side effects. These were correl ated with Nfx nitroreduction to a nitroanion radical followed by superoxide anion generation through a redox cycling process. The aim of this study wa s to verify whether the oral administration of Nfx to Sprague Dawley male r ats (100 mg.kg(-1), pc) produced any observable ultrastructural alteration in the cells of the colonic mucosa. Results showed that 24 h after Nfx admi nistration there were observable alterations in this type of cells. They es sentially consisted of moderate dilatation of their endoplasmic reticulum a nd intense dilatation of their Golgi complex. Already 1 and 3 h after Nfx a dministration, 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 spectrophotomet rically 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 cyto sol had the ability to nitroreduce Nfx. The results obtained show a correla tion between the ultrastructural localization of injury and that of nitrore ductase activity. The intense deleterious effects of Nfx in the Golgi appar atus suggest the potential occurrence of alterations in the synthesis/stora ge of secretory products of the colonic mucosa.