title: Histochemical and ultrastructural changes induced by zidovudine in mitochondria of rat cardiac muscle.
abstract: Zidovudine (azidothymidine, AZT), a drug used in acquired immune deficiency syndrome (AIDS), blocks reverse transcriptase and therefore inhibits human immunodeficiency virus (HIV) replication. We carried out an ultrastructural and histoenzymatic study in rat cardiac muscle. Groups of animals (3 rats per group) were given drinking water with or without AZT (1 or 2 mg AZT/ml). After 30, 60 and 120 days, the hearts were studied by light and electron microscopy. Histochemical analysis of isocitrate, succinic, malic, NADH and NADPH dehydrogenase activities revealed no changes in AZT-treated rats compared with control rats. The ultrastructural study showed a disruption of cristae and an increased size of mitochondria in rats treated with AZT for 30- and 60-days. No alterations were observed in rats that received the 120-day treatment. A statistical analysis based on electron micrographs demonstrated a time-dependent ratio between intact and disrupted mitochondria. Rats that received AZT for 30 days showed a higher number of abnormal mitochondria than rats that received the 60 day treatment. No differences with respect to rat controls were observed in the rats that received AZT for 120 days. We conclude that AZT-induced ultrastructural alterations in cardiac muscle did not modify the histochemical activity of several mitochondrial enzymes.
authors.affiliation: Departamento de Anatomia Patologica, Instituto de Salud Carlos III, Universidad Complutense, Madrid.
authors.forename: M T
authors.initials: MT
authors.lastname: Corcuera Pindado
authors.forename: A
authors.initials: A
authors.lastname: Lopez Bravo
authors.forename: R
authors.initials: R
authors.lastname: Martinez-Rodriguez
authors.forename: A
authors.initials: A
authors.lastname: Picazo Talavera
authors.forename: F
authors.initials: F
authors.lastname: Gomez Aguado
authors.forename: M
authors.initials: M
authors.lastname: Roldan Contreras
authors.forename: M J
authors.initials: MJ
authors.lastname: Perez Alvarez
authors.forename: A
authors.initials: A
authors.lastname: Fernandez Garcia
authors.forename: M J
authors.initials: MJ
authors.lastname: Alonso Martin
mesh_terms: D000818:Animals; D004326:Drinking / Q000187:drug effects; D005260:Female; D006321:Heart / Q000187:drug effects; D006651:Histocytochemistry; D008854:Microscopy, Electron; D008929:Mitochondria, Heart / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure*; D009206:Myocardium / Q000201:enzymology / Q000648:ultrastructure*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016707:Tissue Fixation; D015430:Weight Gain / Q000187:drug effects; D015215:Zidovudine / Q000633:toxicity*
chemical_list: D015215:Zidovudine