Effects of hydroxylated polychlorinated biphenyls on mouse liver mitochondrial oxidative phosphorylation

T. R. Narasimhan, H. L. Kim, S. H. Safe

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

The effects of three tetrachlorobiphenylols [2′,3′,4′,5′‐tetrachloro‐2‐biphenylol (1); 2′,3′,4′,5′‐tetrachloro‐4‐biphenylol (2); and 2′,3′,4′,5′‐tetrachloro‐3‐biphenylol (3)]; three monochlorobiphenylols [5‐chloro‐2‐biphenylol (5), 3‐chloro‐2‐biphenylol (6); and 2‐chloro‐4‐biphenylol (7)] and a tetrachlorobiphenyldiol [3,3′,5,5′‐tetrachloro‐4,4′‐biphenyldiol (4) on respiration, adenosine triphosphatase (ATPase)] activity, and swelling in isolated mouse liver mitochondria have been investigated. Tetrachlorobiphenylols (1–3) and the tetrachlorobiphenyldiol (4) inhibited state‐3 respiration in a concentration‐dependent manner with succinate as substrate (flavin adenine dinucleotide [FAD]‐linked) and the tetrachlorobiphenyldiol (4) caused a more pronounced inhibitory effect on state‐3 respiration than the other congeners. The monochlorobiphenylols 5–7 were less active as inhibitors of state‐3 mitochondrial respiration and significant effects were observed only at higher concentration (≥0.4 μM). However, in the presence of the nicotinamide adenine dinucleotide (NAD)‐linked substrates (glutamate plus malate), hydroxylated PCBs (1–7) significantly inhibited mitochondrial state‐3 respiration in a concentration‐dependent manner. Compounds 5, 6, and 7 uncoupled mitochondrial oxidative phosphorylation only in the presence of FAD‐linked substrate as evidenced by increased oxygen consumption during state‐4 respiratory transition, stimulating ATPase activity, releasing oligomycin‐inhibited respiration, and inducing mitochondrial swelling (5, 6, and 7). Tetrachlorobiphenylols 1, 2, and 3 had no effect on mitochondrial ATPase activity while the tetrachlorobiphenyldiol, 4, decreased the enzyme activity. The possible inhibitory site of electron transport by these compounds and their toxicologic significance is discussed.

Original languageEnglish (US)
Pages (from-to)229-236
Number of pages8
JournalJournal of Biochemical Toxicology
Volume6
Issue number3
DOIs
StatePublished - 1991

ASJC Scopus subject areas

  • Toxicology

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