title: Effects of hepatotoxicants on the induction of microsomal monooxygenase activity in sunfish liver by beta-naphthoflavone and benzo[a]pyrene.
abstract: Effects of chemically induced hepatic injury on biotransformation enzymes in fish were studied. Sunfish hybrids (Lepomis macrochirus x L. cyanellus) were dosed per os with allyl formate (ALF) and carbon tetrachloride (CCl4), and the induction of liver EROD (7-ethoxyresorufin O-deethylase) activity was subsequently challenged by injections of beta-naphthoflavone (BNF) and benzo[a]pyrene (B[a]P). Hepatotoxicity of chemical treatments was assessed using blood enzymes (ASAT, ALAT, and LDH) along with other biochemical variables. Both hepatotoxicants partially abolished the induction of EROD (maximally by 76-89%), and the decrease in induction was dose related. The cytosolic activity of glutathione S-transferase (GST) in the liver decreased in parallel with the decrease in EROD induction. Fish receiving high doses of ALF exhibited significantly less microsomal and blood plasma proteins and, occasionally, were jaundiced. These symptoms, however, were less sensitive indicators of hepatotoxicity than alterations in liver EROD and GST. Both ALF and CCl4 increased the activities of hepatic enzymes in the blood plasma, indicating cytotoxicity. In addition B[a]P, unlike BNF, also increased plasma activities of LDH and ALAT at a dose inducing liver EROD, implying simultaneous hepatotoxicity at high sublethal levels of this xenobiotic. These data suggest that hepatotoxic chemicals absorbed by fish may act antagonistically by decreasing the degree of induction of the cytochrome P450 system relative to the inherent capacity of inducing xenobiotic chemicals present in the environment. Therefore, when assessing the toxicological status of water using fish health biomarkers, it is advisable to measure a concert of metabolic and biochemical variables instead of any single biomarker.
authors.affiliation: Department of Biology, University of Joensuu, Finland.
authors.forename: A
authors.initials: A
authors.lastname: Oikari
authors.forename: B
authors.initials: B
authors.lastname: Jimenez
mesh_terms: D000410:Alanine Transaminase / Q000096:biosynthesis / Q000378:metabolism; D000818:Animals; D001564:Benzo(a)pyrene / Q000494:pharmacology*; D001571:Benzoflavones / Q000494:pharmacology*; D002251:Carbon Tetrachloride / Q000633:toxicity*; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005563:Formic Acid Esters / Q000633:toxicity*; D005982:Glutathione Transferase / Q000096:biosynthesis / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000096:biosynthesis / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D010088:Oxidoreductases / Q000096:biosynthesis / Q000378:metabolism; D010105:Oxygenases / Q000096:biosynthesis*; D010473:Perciformes / Q000378:metabolism*; D019324:beta-Naphthoflavone
chemical_list: D001571:Benzoflavones; D005563:Formic Acid Esters; D001564:Benzo(a)pyrene; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System; C034499:allyl formate; D002251:Carbon Tetrachloride; D010088:Oxidoreductases; D007770:L-Lactate Dehydrogenase; D010105:Oxygenases; D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase; D000410:Alanine Transaminase