The biotoxin okadaic acid (OA), produced by dinoflagellates in marine environment, can accumulate in sponges and shellfish. Consumption of contaminated shellfish induces acute toxic effects such as diarrhea, nausea, vomiting, and abdominal pain. CYP3A4, one of the most important human xenobiotic metabolizing enzymes, is supposed to be involved in the metabolism of OA. Aim of our study was to evaluate the role of CYP3A4 in OA in vitro metabolism as well as in cell cytotoxicity in parallel. Therefore, a metabolic competent HepaRG cell line was exposed to OA with and without addition of the CYP3A4 inhibitor ketoconazole. Without the inhibitor, two mono-hydroxylated metabolites could be identified, whereas in its presence, no metabolites could be detected. Confirmation of the formed metabolites was accomplished by measuring the exact masses and investigating the fragmentation pattern. Data obtained from cytotoxicity assays showed that OA cytotoxicity is reduced when CYP3A4 is active. Thus, hydroxylation appears to be a crucial step for metabolic OA detoxification.
The paper descibes a novel method to detoxify pine wood (Pinus silvestris L.) treated with CCB-, CCF- CC-, and Cu-HDO-type salt preservatives. In the process of biological detoxification organic acids produced by strains of Antrodia vaillantii and other brown rot fungi are used for the dissolution of the previously fixed inorganic compounds. These findings are the basis for applying an acid pulping process (FORMACELL) developed by Nimz and Schone (1992) at the BFH, Hamburg, to detoxify salt impregnated wood waste with a mixture of acetic and formic acid. First results achieved with wood chips from treated poles after approximately 20 years of service life show that the obtained pulp contains less than 100 ppm of Cr and Cu. The pulp properties were neither influenced by the Cr and Cu ions nor by the age of the poles. The extracted quantities of Cr and Cu remain with the lignin whereas the acids are evaporated and recycled in the pulping process.