Acute response of rat liver microsomal lipids, lipid peroxidation, and membrane anisotropy to a single oral dose of polybrominated biphenyls.
Liver microsomal lipids and lipid peroxidation activities were examined in adult male rats at intervals over a 2-mo period after the administration of a single oral dose of 0 or 500 mg/kg of FireMaster BP-6 in corn oil. Microsomal lipids were markedly altered in the polybrominated biphenyl- (PBB-) dosed animals at the earliest time examined (1 wk), and these changes persisted throughout the remainder of the study. An early decrease in the cholesterol-phospholipid ratio was noted, which probably contributed to the significant decrease in the steady-state fluorescence anisotropy demonstrable in both intact microsomes and in liposomes prepared from microsomal lipid extracts. Significant concentrations of PBBs were present in dosed rat microsomes, but the changes in anisotropy appeared to result from membrane lipid alterations rather than from a direct perturbation by PBBs. Iron ascorbate-induced peroxidation was also greatly enhanced in dosed rat microsomes, even when rats were maintained on a low-iron (25 ppm) diet. These early alterations in membrane fluidity and peroxidative capacity of microsomes may ultimately contribute to the hepatotoxicity of PBBs.
D000284:Administration, Oral; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects; D005227:Fatty Acids / Q000032:analysis; D005454:Fluorescence Polarization; D007501:Iron / Q000494:pharmacology; D008054:Lipid Peroxides / Q000378:metabolism*; D008055:Lipids / Q000032:analysis*; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010743:Phospholipids / Q000032:analysis; D011075:Polybrominated Biphenyls / Q000032:analysis / Q000633:toxicity*; D051381:Rats
D005227:Fatty Acids; D008054:Lipid Peroxides; D008055:Lipids; D010743:Phospholipids; D011075:Polybrominated Biphenyls; C015885:Firemaster BP-6; D007501:Iron