[Study of histoenzymatic activity of isocitrate-DH in the hepatic tissue of rats treated with AZT: image analysis]. / Estudio de la actividad histoenzimática isocitrato-DH en tejido hepático de ratas tratadas con AZT mediante análisis de imagen.

OBJECTIVE: Recently has been described alterations in different organs of HIV + patients treated with zidovudine (AZT), as secondary effect from drug administration. METHOD: We have developed and experimental rat model, in which the rats were administered AZT in drinking water and we have analysed the activity of enzyme isocitrate DH, of Krebs cycle, in hepatic tissue sections. Histological technique were employed and image analysis to objectivate the results. RESULTS: A significant statistic decrease of the enzyme activity in those animals treated with AZT were observed, compared with the control groups. CONCLUSIONS: The modification from enzyme activities related with Krebs cycle can be traduced in mitochondrial alterations, that could have direct or indirect influence in the appearance of some associated pathologies to the AZT treatment.

Histochemical and ultrastructural changes induced by zidovudine in mitochondria of rat cardiac muscle.

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.