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, 3.0 mg/kg the circulating T1/2 of enzyme in mice varied from 51 to 74 min and the AUC0–inf values were 6.54 ± 0.46, 8.66 ± 0.59, 9.47 ± 1.45 μg/ml × 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. T1/2 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 μM, 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.
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Data availability
The data sets used and/or analyzed during the current study are available from the corresponding author on request.
Abbreviations
- LO:
-
L-Lysine α-oxidase
- ASNase:
-
L-Asparaginase
- MGL:
-
Methionine–gamma-lyase
- BBB:
-
Blood–brain barrier
- TMB:
-
3,3′,5,5′-Tetramethylbenzidine
- PBS:
-
Phosphate buffered saline
- FBS:
-
Fetal bovine serum
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The publication has been prepared with the support of the «RUDN University Program 5-100.
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VSP conceived of the presented idea, was involved in planning and supervised the work, contributed to the interpretation of the results, drafted the manuscript. GB performed animal experiments, processed the experimental data, performed the analysis, drafted the manuscript and designed the figures. ANL carried out L-lysine α-oxidase determination in serum by enzyme immunoassay, contributed to the interpretation of the results. SShK performed animal experiments. AYuA and AGM isolated and purified LO samples and characterized their activity. MVK performed the statistical analysis and contributed to the interpretation of the results. EVL supervised the project and contributed to the interpretation of the results. All authors discussed the results and contributed to the final manuscript. The final version of the article was approved by all authors.
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This article does not contain any studies with human participants performed by any of the authors. All animal experiments were carried out in compliance with EU directives (European Convention for the Protection of Animals Kept for Experimental and other Scientific Purposes, Strasbourg, 1985; 86/609/EEC and 2010/63/EU) on the protection of animals used for scientific purposes, institutional policy for the proper and humane use of animals in research were followed, the animal studies were approved by the local ethics committee of Peoples’ Friendship University of Russia, the decision from 17/09/2015.
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Communicated by G. J. Peters.
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Pokrovsky, V.S., Lukashev, A.N., Babayeva, G. et al. Plasma pharmacokinetics and tissue distribution of L-lysine α-oxidase from Trichoderma cf. aureoviride RIFAI VKM F- 4268D in mice. Amino Acids 53, 111–118 (2021). https://doi.org/10.1007/s00726-020-02930-4
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DOI: https://doi.org/10.1007/s00726-020-02930-4