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Ergebnisse nach Hochschule und Institut
Publikation Biotransformation of ritalinic acid by laccase in the presence of mediator TEMPO(Elsevier, 07/2018) Kobakhidze, Aza; Elisashvili, Vladimir; Corvini, Philippe; Cvancarova Småstuen, M.Methylphenidate is widely used as a medication for the treatment of attention deficit hyperactivity disorder (ADHD) in children. Less than 1% of methylphenidate is excreted unchanged in urine, while 80% of an oral dose is excreted as ritalinic acid (which is reportedly poorly degradable). This study aims to investigate the biotransformation of ritalinic acid by free and immobilized enzymes. The influence of various laccase mediators on biotransformation efficiency has been tested. Formation of the main transformation products has been monitored and their potential structures suggested. The effective transformation of ritalinic acid was observed only in the presence of 2,2,6,6-tetramethylpiperidine 1-oxyl mediator (TEMPO). The most effective enzyme was the laccase of T. versicolor 159. The main transformation product was an N-methyl derivative of ritalinic acid. Ritalinic acid was also reduced to aldehyde and alcohol, and a broad spectrum of intermediate complexes with oxoammonium ion of TEMPO were detected. This is the first time the biotransformation of ritalinic acid has been investigated in detail.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation ABC transporters and xenobiotic defense systems in early life stages of rainbow trout (Oncorhynchus mykiss)(Elsevier, 02.03.2016) Kropf, Christian; Segner, Helmut; Fent, KarlEmbryos of oviparous fish, in contrast to (ovo) viviparous species, develop in the aquatic environment, and therefore need solute transport systems at their body surfaces for maintaining internal homeostasis and defending against potentially harmful substances. We hypothesized that solute transporters undergo changes in tissue distribution from the embryo to the larval stage. We therefore studied the mRNA profiles of eight ABC transporters (abcb1a, abcb1b, abcc1, abcc2, abcc3, abcc4, abcc5, abcg2) and three solute carriers (oatp1d, putative oatp2 putative, mate1) in different body regions (head, yolk sac epithelium, abdominal viscera, skin/muscles) of developing rainbow trout. Additionally, we investigated mRNA levels of phase I (cyp1a, cyp3a) and phase II (gstp, putative ugt1, putative ugt2) biotransformation enzymes. The study covered the developmental period from the eleuthero-embryo stage to the first-feeding larval stage (1-20days post-hatch, dph). At 1dph, transcripts of abcc2, abcc4, abcg2, cyp3a, gstp, putative mate1, and putative oatp2 occurred primarily in the yolk sac epithelium, whereas at later stages expression of these genes was predominantly observed in the abdominal viscera. The functional activity of ABC transporters in fish early life stages was assessed by rhodamine B accumulation assays. Finally, we investigated the potential impact of xenobiotics (clotrimazole, clofibric acid) on the ABC and biotransformation systems of trout early life stages. While clofibric acid had no effect, clotrimazole lead to an increased rhodamine B accumulation. The results provide evidence that the transition from the eleuthero-embryo to the larval stage is accompanied by a major alteration in tissue expression of ABC transporters.01A - Beitrag in wissenschaftlicher Zeitschrift