Investigations on the metabolism and potentially adverse effects of ethoxyquin dimer, a major metabolite of the synthetic antioxidant ethoxyquin in salmon muscle.

The feed additive ethoxyquin (EQ) is a commonly used synthetic antioxidant preservative in animal feeds. In farmed Atlantic salmon fillets, EQ residues are present, both as the parent compound and as EQ derivatives. One of the main EQ derivates in fish muscle is an ethoxyquin dimer (EQDM), and the potential toxicity of this metabolite is not known. The aim of this study was to evaluate the metabolism and potentially toxicological effects of EQDM. A 90-day subchronic exposure study with repeated dietary exposure to EQDM at 12.5 mg/kg of body weight per day was performed with male F344 rats. Hepatic Cyp1a1 mRNA was significantly reduced to <3% of the control in rats fed EQDM, and hepatic Cyp2b1 mRNA was increased to 192%. EQDM increased Gstpi1 mRNA expression to 144% that of the control, but the activity level of this phase II enzyme was reduced. Biomarkers of liver and kidney function did indicate adverse effects of EQDM when F344 rats were fed 12.5 mg/kg of body weight per day. The present study revealed that EQDM produces responses that are comparable to those produced by the parent compound (EQ) in terms of activating the same enzyme systems.

Levels of synthetic antioxidants (ethoxyquin, butylated hydroxytoluene and butylated hydroxyanisole) in fish feed and commercially farmed fish.

Several synthetic antioxidants are authorized for use as feed additives in the European Union. Ethoxyquin (EQ) and butylated hydroxytoluene (BHT) are generally added to fish meal and fish oil, respectively, to limit lipid oxidation. The study was conducted to examine the concentrations of EQ, BHT and butylated hydroxyanisole (BHA) in several commercially important species of farmed fish, namely Atlantic salmon, halibut and cod and rainbow trout, as well as concentrations in fish feed. The highest levels of BHT, EQ and BHA were found in farmed Atlantic salmon fillets, and were 7.60, 0.17 and 0.07 mg kg(-1), respectively. The lowest concentrations of the synthetic antioxidants found were in cod. The concentration of the oxidation product ethoxyquin dimer (EQDM) was more than ten-fold higher than the concentration of parent EQ in Atlantic salmon halibut and rainbow trout, whereas this dimer was not detected in cod fillets. The theoretical consumer exposure to the synthetic antioxidants EQ, BHA and BHT from the consumption of farmed fish was calculated. The contribution of EQ from a single portion (300 g) of skinned fillets of the different species of farmed fish would contribute at most 15% of the acceptable daily intake (ADI) for a 60 kg adult. The consumption of farmed fish would not contribute measurably to the intake of BHA; however, a 300 g portion of farmed Atlantic salmon would contribute up to 75% of the ADI for BHT.

[Remifentanil and alfentanil: Sympathetic-adrenergic effect in the first postoperative phase in patients at cardiovascular risk]. / Remifentanil und Alfentanil: Sympathiko-adrenerge Effekte in der frühen postoperativen Phase beim kardiovaskulären Risikopatienten.

UNLABELLED: Extubation and the immediate postoperative period are critical periods with strong sympatho-adrenergic stimulation. The aim of the present study was to investigate this period after balanced anaesthesia with remifentanil and alfentanil in cardiac risk patients. METHODS: 52 patients with coronary artery disease or with risk factors for coronary heart disease scheduled for elective extraperitoneal and extrathoracic operation were included in this study. Anaesthesia was induced by intravenous administration of etomidate, vecuronium and remifentanil (n = 27, 1 microgram/kg) or alfentanil (n = 25, 25 micrograms/kg). Anaesthesia was maintained with an Isoflurane/N2O/O2 mixture and by continuous intravenous infusion of remifentanil (0.25 microgram/kg/min) or alfentanil (45 micrograms/kg/h). During the first 60 minutes after extubation haemodynamic parameters were monitored and catecholamines were determined at defined time intervals. Parameters of recovery, the requirement of analgesics and cardiac medications were compared in both groups. Myocardial ischaemia was assessed by two-channel Holter electrocardiography. RESULTS: The beginning of spontaneous respiration and time of extubation were similar in both groups. The time interval until opening eyes and the time between the beginning of spontaneous respiration and extubation was shorter in the patients treated with remifentanil. In this group patients suffered earlier from pain and had a higher pain score. Although the plasma catecholamines were comparable in both groups, in the patients treated with remifentanil changes in haemodynamic parameters were more pronounced. The incidence of shivering and the requirements of analgesics and cardiac medications were higher in these patients. The incidence of ST-segment changes indicating myocardial ischaemia was similar. CONCLUSIONS: After balanced anaesthesia with remifentanil a more pronounced sympatho-adrenergic stimulation occurs because of the more rapid clearance of the analgesic effect in the recovery period compared to alfentanil requiring more analgesics and medications for the control of the haemodynamic parameters. Because of these specific pharmacological effects the use of remifentanil in cardiac risk patients has to be critically discussed.