Depression of mouse liver microsomal mixed function oxidase enzymes by adriamycin |
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Authors: | A M Mungikar B P Gothoskar |
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Institution: | Biological Chemistry Division, Cancer Research Institute, Tata Memorial Centre, Parel, Bombay, 400 012 India |
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Abstract: | Levels of cytochrome P-450 and cytochrome b5, and activities of NADPH cytochrome c reductase and 7-ethoxycoumarin O-deethylase, were found to be significantly decreased in hepatic microsomes prepared from mice killed 24 h after administration of a single intraperitoneal (i.p.) dose of adriamycin (ADR, 5 mg/kg). In contrast, both ascorbate-induced lipid peroxidation and conjugated dienes were increased in the same preparations. In vitro addition of ADR (5 micrograms/ml) to hepatic microsomal preparations (1 mg/ml protein) from the control mice also led to a substantial decrease in the mixed function oxidase (MFO) enzymes. A characteristic spectral change with an absorption peak at 408 nm and trough at 422 nm was associated with this in vitro interaction. It is suggested that the loss of cytochrome P-450 and related MFO enzymes due to ADR treatment is related to the generation of free radicals and subsequent lipid peroxidation in the liver. |
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Keywords: | Adriamycin mixed function oxidase lipid peroxidation ADR binding spectra ADR adriamycin MFO mixed function oxidase |
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