Toxicity of PBBs with special reference to porphyrinogenic action and spectral interaction with hepatic cytochrome P-450.
Some of the polyhalogenated aromatic compounds (PHAs) which are able to produce porphyria are presently known as environmental contaminants. Chronic exposure to PHAs causes hepatic porphyria in different species. Qualitatively PBBs act comparable to PHAs. An increase in accumulation of porphyrins caused by PHAs is not simply related to an increase of delta-ALAS activity in liver. Heme cannot exert a feedback when porphyria develops. Induction of P-450 mediated drug enzymes is needed. The PHAs interact with P-450 in vitro. The PHAs are converted into a reactive intermediate, not a known metabolite, which depletes liver GSH and then becomes reactive to tissue structures. Mitochondria are damaged; fluorescence of porphyrins is detected in the region of central veins where degenerative change in hepatocytes is most marked. A possible pathological change in the cell membrane permeability is assumed too. In this porphyric stage uropophyrinogen decarboxylase (urogen decarboxylase) is inhibited. The proportion of steroid hormones product by ovaries and testes compared to each other are possibly involved in sensitivity to porphyrinogenic compounds.
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001646:Bile / Q000378:metabolism; D001713:Biphenyl Compounds / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005969:Glutamate Dehydrogenase / Q000097:blood; D006418:Heme / Q000096:biosynthesis; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D008297:Male; D011075:Polybrominated Biphenyls / Q000633:toxicity*; D011164:Porphyrias / Q000139:chemically induced; D011165:Porphyrinogens / Q000096:biosynthesis*; D011166:Porphyrins / Q000096:biosynthesis; D011784:Quail
D001713:Biphenyl Compounds; D011075:Polybrominated Biphenyls; D011165:Porphyrinogens; D011166:Porphyrins; D006418:Heme; D003577:Cytochrome P-450 Enzyme System; D005969:Glutamate Dehydrogenase; D000410:Alanine Transaminase