Lipid emulsion reduces subacute toxicity of amphotericin B: a histopathological study

In previous work acute toxic effects of amphotericin B (AB) were reduced in both in vitro and in vivo tests when AB was associated with a triglyceride -rich emulsion (AB-emulsion). The present paper compares the severity of th e histopathological alterations as determined by morphometry produced in th e target tissues (kidneys, liver, and lungs) by AB-emulsion with those prod uced by the conventional formulation AB-deoxycholate (DOC) following subacu te AB treatment. No morphological alterations were seen in the spleen and h eart following both AB-DOC and AB-emulsion treatment. Although the alterati ons in the liver, kidneys and lungs are basically the same for both formula tions, the intensity of the changes varies considerably. AB-emulsion always caused statistically decreased severity of morphologic alterations, compar ed to AB-DOC by stereological measurements, for the three treatment regimes of AB-administration, These three treatment regimens consisted of 1 mg AB/ kg of body weight every 48 hours for 20 days, 2 mg AB/kg of body weight eve ry 48 hours for 12 days, and 2 mg AB/kg of body weight for 4 consecutive da ys. Thus, these regimens consisted of total doses varying from 8-12 mg/kg o f body weight. Specifically, these morphological changes included proximal and distal tubular edema, inflammation and tubular cell degeneration in the kidney and a moderate inflammation of the portal region in the liver. Vacu olization of hepatocytes only occurred for AB-DOC treatment. In addition, a cute interstitial inflammation was observed in the lungs prior to interstit ial and alveolar edema. The intensity of the histopathological damage incre ase with the dose and with the reduction in the time interval between AB ad ministrations. Abnormal serum biochemical parameters were observed for seru m urea which was higher for both treated AB-groups, as compared to control, and for iron which was lower for the AB-DOC group. In conclusion, the decr eased severity of the morphological alterations in the kidneys, liver, and lungs following subacute treatment with AB-emulsion, as compared to AB-DOC formulation, confirms our previous results consisting of acute toxic effect s induced by in vitro and in vivo tests with AB-emulsion treatment.