COMPARATIVE XENOBIOTIC BIOTRANSFORMATION IN PRECISSION-CUT LIVER SLICES FROM SWINE AND CATTLE

MIRÓ, M.V.; VIVIANI, P.; HERRERA, J.; MATÉ, L.; LANUSSE, C.; LIFSCHITZ, A.L.; VIRKEL, G.L.

Mar del Plata

Congreso; 51° REUNION ANUAL DE LA SOCIEDAD ARGENTINA DE FARMACOLOGÍA EXPERIMENTAL (SAFE); 2019

Species differences in the pattern of metabolism of foreign compounds is a key issue for veterinary practitioners. Comparative studies on the in vitro hepatic metabolism of xenobiotics among different farm animals requires the use of consistent and robust methodologies. The aim of the current work was to validate the technique of precision-cut liver slices (LSs) for comparative studies on xenobiotic metabolism in swine and cattle. Swine (n=3) and bovine (n=6) liver samples were obtained from local abattoirs. LSs (around 20 mg wet weight) were produced by operating a Brendel-Vitron? tissue slicer filled with oxygenated ice-cold Krebs buffer. LSs were cultured (up to 6 h) in Williams? Medium E at 37°C under a humidified atmosphere (95% O2:5% CO2). Tissue viability was assessed by histopathology and the measurement of intracellular reduced (GSH) and oxidized (GSSG) glutathione. The assayed enzyme activities were: benzydamine N-oxidase (BZ N-ox, flavin-containing monooxygenase), ethoxyresorufin O-deethylase (EROD, cytochrome P450 1A1) and methoxyresorufin O-demethylase (MROD, cytochrome P450 1A2). The S-oxidation of the anthelmintic drugs albendazole (ABZ) and fenbendazole (FBZ) was also assessed. HPLC analysis was performed and the rates of appearance of the metabolites in the incubation medium were calculated. Similar BZ N-ox and EROD activities were observed in both species. Conversely, MROD was 2.6-fold higher (p