Hepatic morphological alterations induced by zidovudine (ZDV) in an experimental model

Zidovudine (AZT) inhibits HIV replication. Many studies have demonstrated its toxic myopathic effect in both HIV-positive patients treated with the drug and experimental animal models. So far hepatic lesions induced by AZT have not been reported. In our study, an experimental rat model was used in which the rats were administered AZT (1 mg/ml) in drinking water; histological and ultrastructural alterations were observed in the liver of treated animals and compared with the findings in control animals. The histological alterations detected were turbid swelling, vacuolar degeneration and microvacuolar fatty degeneration of panlobular distribution; these lesions were progressively greater as the duration of treatment increased. The ultrastructural alterations detected involved the mitochondria (similar to those described in cardiac muscle), smooth and rough endoplasmic reticulum (SER and RER), and the accumulation of fat and glycogen in the hepatocytes of treated animals. The histopathological and ultrastructural findings in our experimental model suggest hepatotoxicity induced by AZT or its catabolites in treated, as compared to control animals.