Effects of nifurtimox or benznidazole administration on rat testes: ultrastructural observations and biochemical studies.
Ultrastructural and biochemical alterations in testes of Sprague-Dawley rats receiving either nifurtimox (Nfx) or benznidazole (Bz) (both 100 mg/kg po) were studied. Nfx produced intense deleterious effects on Steroli cells consisting of dilatation of endoplasmic reticulum and perinuclear membrane, alterations in shape and size of mitochondria, increased lysosomal activity, detachment of ribosomes, and alterations in shape and configuration of spermatids and mature spermatozoa. Bz induced alterations were similar in nature but far less intense and observable only in some cells or preparations or animals but not in others. Testicular Nfx but not Bz nitroreductase activity was detected in microsomal and cytosolic fractions. Microsomal Nfx nitroreductase activity was not inhibited by CO. The cytosolic activity in the presence of hypoxanthine was inhibited by allopurinol and that in the presence of N-methylnicotinamide was inhibited by menadione. All these enzymatic activities were inhibitable by oxygen except the cytosolic one in the presence of N-methylnicotinamide. No evidence for lipid peroxidation was found in testes from Nfx treated animals. Covalent binding of Bz reductive metabolites to testicular proteins and phospholipids was found. Toxicological and pharmacological implications for patients suffering Chagas' disease and receiving these drugs were analyzed.
D000818:Animals; D001711:Biotransformation; D003600:Cytosol / Q000201:enzymology; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000648:ultrastructure; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D008854:Microscopy, Electron; D008861:Microsomes / Q000201:enzymology / Q000378:metabolism; D009547:Nifurtimox / Q000494:pharmacology*; D009581:Nitrofurans / Q000494:pharmacology*; D009593:Nitroimidazoles / Q000378:metabolism / Q000494:pharmacology*; D009601:Nitroreductases / Q000378:metabolism; D009940:Organoids / Q000187:drug effects / Q000648:ultrastructure; D010743:Phospholipids / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D012708:Sertoli Cells / Q000187:drug effects / Q000648:ultrastructure; D013094:Spermatozoa / Q000187:drug effects / Q000648:ultrastructure; D013737:Testis / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure
D008054:Lipid Peroxides; D009581:Nitrofurans; D009593:Nitroimidazoles; D010743:Phospholipids; D009601:Nitroreductases; D009547:Nifurtimox; C009999:benzonidazole