Abstract
L-lysine α-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, 3.0mg/kg the circulating T1/2 of enzyme in mice varied from 51 to 74min and the AUC0-inf values were 6.54 ± 0.46, 8.66 ± 0.59, 9.47 ± 1.45μg/ml × h, respectively. LO was distributed in tissues and determined within 48h after administration with maximal accumulation in liver and heart tissues. Mean time to reach the maximum concentration was highest for the liver-9h, kidney-1h and 15min for the tissues of heart, spleen and brain. T1/2 of LO in tissues ranged from 7.75 ± 0.73 to 26.10 ± 2.60h. In mice, plasma L-lysine decreased by 79% 15min after LO administration in dose 1.6mg/kg. The serum L-lysine levels remained very low from 1 to 9h (< 25μM, 17%), indicating an acute lack of L-lysine in animals for at least 9h. Concentration of L-lysine in serum restored only 24h 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.
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