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

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. © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH, AT part of Springer Nature.

Авторы
Pokrovsky V.S. 1, 2 , Lukashev A.N. 3 , Babayeva G. 1, 2 , Karshieva S.S.2 , Arinbasarova A.Y.4 , Medentzev A.G. 4 , Komarova M.V. 5 , Lukasheva E.V. 1
Журнал
Номер выпуска
1
Язык
Английский
Страницы
111-118
Статус
Опубликовано
Том
53
Год
2021
Организации
  • 1 Department of Biochemistry, Peoples’ Friendship University, Moscow, Russian Federation
  • 2 Laboratory of Combined Treatment, N.N. Blokhin Cancer Research Center, Moscow, Russian Federation
  • 3 Tropical and Vector Borne Diseases, Martsinovsky Institute of Medical Parasitology, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation
  • 4 G.K. Skryabin Institute of Biochemistry and Physiology of Microorganisms, Russian Academy of Sciences, Moscow Region, Russian Federation
  • 5 Department of Laser and Biotechnical Systems, Samara University, Samara, Russian Federation
Ключевые слова
L-Amino acid oxidase; L-Lysine depletion; L-Lysine α-oxidase; Pharmacokinetics; Tissue distribution
Дата создания
20.04.2021
Дата изменения
20.04.2021
Постоянная ссылка
https://repository.rudn.ru/ru/records/article/record/72383/
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