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The effect of inorganic lead on heptic biochemical and ultrastructural changes produced by phenobarbital
Abstract:
Lead acetate (105 mumol/kg, i.p.) decreased rat hepatic cytochrome P-450 to 57% and 63% of control values when measured 24 and 48 h after lead administration, respectively. A large increase in urinary delta-aminolevulinic acid (U-ALA) was observed after lead treatment, indicating a depression of heme synthesis. In addition, lead treatment produced dilated cisternae of the smooth endoplasmic reticulum (SER). Phenobarbital (100 mg/kg, i.p.) produced an induction of cytochrome P-450, proliferation of the SER, and did not alter U-ALA content. Simultaneous lead and phenobarbital treatment produced a delayed but robust induction of cytochrome P-450, only a moderate rise in U-ALA, and a reduced proliferation of the SER of hepatocytes. Therefore, phenobarbital, an inducer of heme synthetic enzymes, is apparently capable of reversing lead-induced inhibition of heme synthesis as measured by hepatic cytochrome P-450 induction and U-ALA content.
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