DOI: 10.24075/brsmu.2019.044


Toxicity of 13C-labeled linoleic and linolenic acids for diagnostic breath tests

Tynio YaYa1, Morozova GV2, Biryukova YuK3,4, Trubnikova EV3, Zylkova MV4, Sivokhin DA5, Ivanov KP6, Pozdniakova NV7, Kazakova EA8, Mutnykh ES9, Shevelev AB9,10
About authors

1 Russian State University of Physical Education, Sport, Youth and Tourism, Moscow, Russia

2 Skryabin Moscow State Academy of Veterinary Medicine and Biotechnology, Moscow, Russia

3 Kursk State University, Kursk, Russia

4 Chumakov Federal Scientific Center for Research and Development of Immune and Biological Products, Russian Academy of Sciences, Moscow, Russia

5 Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia

6 Bakulev Center for Cardiovascular Surgery Moscow, Russia

7 Blokhin National Medical Research Center of Oncology, Moscow, Russia

8 National Research University Higher School of Economics, Moscow, Russia

9 Vavilov Institute of General Genetics, Moscow, Russia

10 Plekhanov Russian University of Economics, Moscow, Russia

Correspondence should be addressed: Yulia K. Biryukova
Kosygina 4, Moscow, 119334; ur.liam@alu-avokuirib

About paper

Funding: this study was part of the State Project 0112-2019-0001 on Genomic studies and genetic polymorphism of the cell, organism and population headed by Yankovsky NK.

Author contribution: Tynio YaYa, Morozova GV — synthesis of 13C-labeled linoleic acid; Biryukova YuK — blood biochemistry tests; Trubnikova EV — statistical analysis; Zylkova MV — preparation of histological slides; Sivokhin DA — literature analysis, manuscript draft; Ivanov KP — animal sacrifice and necropsy; Pozdniakova NV, Mutnykh ES — acute toxicity tests of 13C-labeled acids following their single administration; Kazakova EA — subchronic toxicity tests of 13C-labeled acids; Shevelev AB — study conception, analysis and discussion of its results.

Received: 2019-06-24 Accepted: 2019-06-30 Published online: 30.06.2019

Noninvasive stable isotope breath tests allow highly accurate and safe estimation of liver and biliary tract function. The aim of this study was to test 13С-labeled linoleic and linolenic acids intended for diagnostic use for acute and subchronic toxicity. The acids were synthesized using the patented method. A single intragastric administration of the tested compounds to experimental BALB/c mice and Wistar rats in the amounts exceeding clinical doses 500 to 2500-fold did not cause animal death. In the subchronic toxicity test, the rats received 5 to 25 times higher doses than recommended for clinical use in humans. In a 14-day follow-up period, no significant differences were observed between the main and the control groups in terms of weight, blood count (red blood cells, white blood cells, platelets), and blood biochemistry (hemoglobin, total protein, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, bilirubin). The studied compounds are safe at doses intended for oral administration and are recommended for further preclinical and clinical trials.

Keywords: breath test, linoleic acid, linolenic acid, carbon-13