No abstract

No abstract

No abstract

The interactions of fibrate (clofibrate, fenofibrate, bezafibrate, gemfibrozil), antiinflammatory (ibuprofen, diclofenac, naproxen, ketoprofen), and anti-depressive (fluoxetine,fluvoxamine, paroxetine) drugs with CYP catalyzed pathways (CYP1A, CYP3A-, CYP2K-, and CYP2M-like) and Phase II activities (UDP-glucuronosyltransferases and sulfotransferases), involved in both xenobiotic and endogenous metabolism in fish, were investigated in-vitro by incubating carp liver subcellular fractions in the presence of the substrate and the selected drug. Anti-depressive drugs were strong inhibitors of CYP1A (92-94% inhibition), CYP3A-like (69-80% inhibition), and CYP2K-like (36-69% inhibition) catalyzed activities, while antiinflammatory drugs were potent CYP2M-like inhibitors (32-74% inhibition). Among the lipid regulators, gemfibrozil strongly inhibited CYP2M-catalyzed activity (91% inhibition) and other CYP isoforms (CYP1A and CYP3A-like). Additionally, glucuronidation of naphthol and testosterone were targeted by antiinflammatory drugs, and to a lesser extent, by fibrate drugs (48-78% inhibition). No significant alteration on sulfotransferase activities was observed, apart from a minor inhibitory effect of clofibrate, gemfibrozil, and fluoxetine on the sulfation of estradiol. Overall, gemfibrozil, diclofenac, and the three anti-depressive drugs appear to be the pharmaceuticals with the highest potential to interfere with fish metabolic systems.

No abstract

No abstract

No abstract

Metabolic capabilities of PLHC-1 and RTL-W1 cell lines were investigated since to date, cytochrome P450 (CYP) 1A and glutathione-S-transferase have been almost the unique biotransformation enzymes reported in these cells. Functionality of CYP3A-, CYP2M- and CYP2K-like enzymes was assessed by studying the hydroxylation of testosterone (T) and lauric acid (LA), and glucuronidation and sulfation capacity was assessed by looking at 1-naphthol (1-N) and T conjugation. Only PLHC-1 cells showed the ability to hydroxylate T at 6beta-position (a CYP3A-like catalysed pathway) and LA at (omega-1)-position (a CYP2K-like catalysed pathway). Hydroxysteroid dehydrogenase and steroid reductase enzymes showed comparatively higher activities than CYPs: 5alpha-dihydrotestosterone, androstenedione and 3beta-androstanediol were the major metabolites of T detected in both cell lines. Regarding phase II activities, both cell lines metabolised 1-N to glucuronide and sulfate conjugates. In contrast, when using T as substrate, RTL-W1 formed the glucuronide, whilst PLHC-1 formed the corresponding sulfate. Overall, the observed enzymatic activities are much lower (up to 17.5 x 10(3) times) than those reported in primary cultures of fish hepatocytes. The present study highlights the need of developing new fish cell lines that could be used as alternative in vitro tools for studying xenobiotic metabolism and toxicity in fish.