Effect of amphotericin B on hepatic cytochrome P-450 and glucose-6-phosphatase in the rat

• Published in: Journal of hepatology Vol. 14; no. 2-3; p. 300
• Main Authors: Heidemann, H, Holzlöhner, U, Heydemann, J, Freitag, T, Inselmann, G
• Format: Journal Article
• Language: English
• Published: Netherlands 01-03-1992
• Subjects: Amphotericin B - pharmacology; Analysis of Variance; Animals; Antipyrine - metabolism; Cytochrome P-450 Enzyme System - metabolism; Glucose-6-Phosphatase - metabolism; Kinetics; Liver - drug effects; Liver - metabolism; Male; Malondialdehyde - metabolism; Microsomes, Liver - drug effects; Microsomes, Liver - enzymology; Organ Size - drug effects; Rats; Rats, Inbred Strains; Reference Values
• ISSN: 0168-8278
• DOI: 10.1016/0168-8278(92)90174-N

The effect of amphotericin B on hepatic microsomal cytochrome P-450 (P-450) concentration was measured in vitro, in vivo and ex vivo in the rat. In vitro, both amphotericin B (0-500 micrograms/ml) and its vehicle, sodium deoxycholate (0-410 micrograms/ml), caused similar dose-dependent decreases of P-450 concentrations and glucose-6-phosphatase activity. Intravenous amphotericin B (3 mg/kg) given daily for 3 days decreased antipyrine clearance from control values of 1.24 +/- 0.24 ml/min to 0.67 +/- 0.12 ml/min (p less than 0.001); whereas antipyrine clearance was unchanged by sodium deoxycholate. The P-450 concentration on the third day was reduced from 0.74 +/- 0.14 nmol/mg protein in control rats to 0.33 +/- 0.09 nmol/mg protein in rats treated with amphotericin B (p less than 0.001). Sodium deoxycholate had no effect on P-450 concentration. In contrast, amphotericin B had no effect on either antipyrine clearance or P-450 concentration following enzyme induction by phenobarbital. Amphotericin B had no effect on microsomal glucose-6-phosphatase activity in vivo. Neither amphotericin B nor sodium deoxycholate induced lipid peroxidation, measured as malondialdehyde production. These results show that amphotericin B decreases hepatic cytochrome P-450 content and function in the rat. These effects can not be observed in the enzyme induced state. Amphotericin B has no effect on glucose-6-phosphatase in vivo, the key enzyme of the gluconeogenesis, indicating selective effects on hepatic microsomal function.