The effect of inorganic lead on heptic biochemical and ultrastructural changes produced by phenobarbital.
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.
D000622:Aminolevulinic Acid / Q000032:analysis; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D004721:Endoplasmic Reticulum / Q000187:drug effects; D006418:Heme / Q000096:biosynthesis; D007854:Lead / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D008297:Male; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D007854:Lead; D006418:Heme; D000622:Aminolevulinic Acid; D003577:Cytochrome P-450 Enzyme System; D010634:Phenobarbital