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Sex-specific biotransformation and detoxification after xenobiotic exposure of primary cultured hepatocytes of European flounder (Platichthys flesus L.)
Winzer, K.; Van Noorden, C.J.F.; Köhler, A. (2002). Sex-specific biotransformation and detoxification after xenobiotic exposure of primary cultured hepatocytes of European flounder (Platichthys flesus L.). Aquat. Toxicol. 59(1-2): 17-33
In: Aquatic Toxicology. Elsevier Science: Tokyo; New York; London; Amsterdam. ISSN 0166-445X, more
Peer reviewed article  

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Keywords
    Antioxidants; Biotransformation; Fish culture; Hydrogen peroxide; Hydrogen peroxide; Hydrogen peroxide; Nitrofurantoin; Oxidation; Sex hormones; Platichthys flesus (Linnaeus, 1758) [WoRMS]; Marine; Brackish water; Fresh water

Authors  Top 
  • Winzer, K.
  • Van Noorden, C.J.F.
  • Köhler, A., correspondent

Abstract
    Sex-specific effects of sublethal concentrations of known effective pro-oxidants such as 100, 200 and 400 µM benzo[a]pyrene (B[a]p), 50 µM nitrofurantoin (NF) and 100 µM hydrogen peroxide (H2O2) on biotransformation pathways were studied in isolated hepatocytes of immature female and male European flounder (Platichthys flesus L.). Cell responses were assessed at the level of: (1) stress induction as measured by formation of reactive oxygen species (ROS), mainly superoxide radicals, and induction of cytochrome P450 (CYP450) biotransformation activity; (2) cellular antioxidant defences, both non-enzymatic (reduced glutathione) and enzymatic (DT-diaphorase (DTD) or quinone oxidoreductase, EC 1.6.99.2); (3) detoxification (aldehyde dehydrogenase (ALDH), EC 1.2.1.3); and (4) cellular damage as measured by reduced lysosomal membrane stability and cell death. As there is increasing evidence that 17-β-estradiol interferes with certain pathways of xenobiotic biotransformation, we additionally tested the effects of different concentrations of 17-β-estradiol (0.2-10 µM) alone and 17-β-estradiol (1 µM) in combination with 100 µM B[a]p. Parameters were monitored after 1 and 9 days of exposure by quantitative image analysis of chromogenic or fluorogenic reaction products. Our study revealed sex-dependent differences in cellular stress responses. In hepatocytes of female flounder, biotransformation was slower and the capacity of non-enzymatic antioxidant defences and detoxification of toxic aldehydes was lower than in males. Additional administration of 17-β-estradiol enlarged these differences between the sexes with respect to biotransformation activity and antioxidant defence in xenobiotic-induced injury. These findings may explain the higher susceptibility of female flounder to toxic and carcinogenic compounds in the marine environment.

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