Plasma pharmacokinetics and tissue distribution of L-lysine alpha-oxidase from Trichoderma cf. aureoviride RIFAI VKM F-4268D in mice

摘要

L-lysine alpha-oxidase (LO) is an L-amino acid oxidase with antitumor, antimicrobial and antiviral properties. Pharmacokinetic (PK) studies were carried out by measuring LO concentration in plasma and tissue samples by enzyme immunoassay. L-lysine concentration in samples was measured spectrophotometrically using LO. After single i.v. injection of 1.0, 1.5, 3.0 mg/kg the circulating T-1/2 of enzyme in mice varied from 51 to 74 min and the AUC(0-inf) values were 6.54 +/- 0.46, 8.66 +/- 0.59, 9.47 +/- 1.45 mu g/ml x h, respectively. LO was distributed in tissues and determined within 48 h after administration with maximal accumulation in liver and heart tissues. Mean time to reach the maximum concentration was highest for the liver-9 h, kidney-1 h and 15 min for the tissues of heart, spleen and brain. T-1/2 of LO in tissues ranged from 7.75 +/- 0.73 to 26.10 +/- 2.60 h. In mice, plasma L-lysine decreased by 79% 15 min after LO administration in dose 1.6 mg/kg. The serum L-lysine levels remained very low from 1 to 9 h (< 25 mu M, 17%), indicating an acute lack of L-lysine in animals for at least 9 h. Concentration of L-lysine in serum restored only 24 h after LO administration. The results of LO PK study show that it might be considered as a promising enzyme for further investigation as a potential anticancer agent.