A Study of Embryotoxic, Foetotoxic, and Teratogenic Effects of the Original Antituberculosis Agent Thiozonide in Pregnant Rabbits
Several treatment regimens with antituberculosis medicinal products are available for tuberculosis. Thiozonide is a newly developed original antimicrobial agent that exhibits bacteriostatic activity against Mycobacterium tuberculosis strains H37Rv, CN-37, CN-40, and MS-115.The aim of the study was t...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | Russian |
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Ministry of Health of the Russian Federation, Federal State Budgetary Institution «Scientific Centre for Expert Evaluation of Medicinal Products»
2023-06-01
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| Series: | Безопасность и риск фармакотерапии |
| Subjects: | |
| Online Access: | https://www.risksafety.ru/jour/article/view/362 |
| _version_ | 1797224540082798592 |
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| author | A. Yu. Borodina K. L. Kryshen A. Yu. Savchenko M. N. Makarova V. G. Makarov |
| author_facet | A. Yu. Borodina K. L. Kryshen A. Yu. Savchenko M. N. Makarova V. G. Makarov |
| author_sort | A. Yu. Borodina |
| collection | DOAJ |
| description | Several treatment regimens with antituberculosis medicinal products are available for tuberculosis. Thiozonide is a newly developed original antimicrobial agent that exhibits bacteriostatic activity against Mycobacterium tuberculosis strains H37Rv, CN-37, CN-40, and MS-115.The aim of the study was to investigate the embryotoxic, foetotoxic, and teratogenic effects of thiozonide in pregnant rabbits.Materials and methods. The study involved 66 pregnant rabbits (4 groups of 16–17 animals each). The rabbits received oral thiozonide from day 6 to day 19 of gestation at doses of 20.6 mg/kg (1 TD (therapeutic dose)), 103 mg/kg (5 TDs), and 206 mg/kg (10 TDs). The control group received a 1% starch solution. The authors conducted a macroscopic examination of the reproductive organs and a histological evaluation of the placenta in eutha nised pregnant rabbits. Live foetuses underwent a check for developmental abnormalities, a skeletal development evaluation with a modified Dawson’s method, and a histologic examination of the internal organs.Results. The study showed no clinical signs of toxicity and no mortality associated with thiozonide in pregnant rabbits across all dose groups. Macroscopic and histological examinations revealed no pathological changes in the reproductive organs of pregnant rabbits. The evaluation of embryotoxic and foetotoxic effects did not identify any differences between the foetuses of the animals assigned to different doses of thiozonide and the control group. The authors found no developmental abnormalities in the foetuses. Examinations of foetal skeleton development and internal organ condition identified no differences between the groups and no abnormalities. The authors registered the death of all foetuses (late resorption) in one rabbit from the 206 mg/kg group. Therefore, the 103 mg/kg dose (5 TDs) was selected as a reasonable No Observed Adverse Effect Level (NOAEL).Conclusions. Thiozonide has no embryotoxic, foetotoxic, or teratogenic effects. |
| first_indexed | 2024-03-08T22:26:28Z |
| format | Article |
| id | doaj.art-7d0f4967f53048838d69d12e030f0abb |
| institution | Directory Open Access Journal |
| issn | 2312-7821 2619-1164 |
| language | Russian |
| last_indexed | 2024-04-24T13:54:44Z |
| publishDate | 2023-06-01 |
| publisher | Ministry of Health of the Russian Federation, Federal State Budgetary Institution «Scientific Centre for Expert Evaluation of Medicinal Products» |
| record_format | Article |
| series | Безопасность и риск фармакотерапии |
| spelling | doaj.art-7d0f4967f53048838d69d12e030f0abb2024-04-03T17:56:38ZrusMinistry of Health of the Russian Federation, Federal State Budgetary Institution «Scientific Centre for Expert Evaluation of Medicinal Products»Безопасность и риск фармакотерапии2312-78212619-11642023-06-0111219120310.30895/2312-7821-2023-11-2-191-204297A Study of Embryotoxic, Foetotoxic, and Teratogenic Effects of the Original Antituberculosis Agent Thiozonide in Pregnant RabbitsA. Yu. Borodina0K. L. Kryshen1A. Yu. Savchenko2M. N. Makarova3V. G. Makarov4Research-and-manufacturing company “HOME OF PHARMACY”Research-and-manufacturing company “HOME OF PHARMACY”Scientific Center of Biomedical Technology of the Federal Medical-Biological Agency of RussiaResearch-and-manufacturing company “HOME OF PHARMACY”Research-and-manufacturing company “HOME OF PHARMACY”Several treatment regimens with antituberculosis medicinal products are available for tuberculosis. Thiozonide is a newly developed original antimicrobial agent that exhibits bacteriostatic activity against Mycobacterium tuberculosis strains H37Rv, CN-37, CN-40, and MS-115.The aim of the study was to investigate the embryotoxic, foetotoxic, and teratogenic effects of thiozonide in pregnant rabbits.Materials and methods. The study involved 66 pregnant rabbits (4 groups of 16–17 animals each). The rabbits received oral thiozonide from day 6 to day 19 of gestation at doses of 20.6 mg/kg (1 TD (therapeutic dose)), 103 mg/kg (5 TDs), and 206 mg/kg (10 TDs). The control group received a 1% starch solution. The authors conducted a macroscopic examination of the reproductive organs and a histological evaluation of the placenta in eutha nised pregnant rabbits. Live foetuses underwent a check for developmental abnormalities, a skeletal development evaluation with a modified Dawson’s method, and a histologic examination of the internal organs.Results. The study showed no clinical signs of toxicity and no mortality associated with thiozonide in pregnant rabbits across all dose groups. Macroscopic and histological examinations revealed no pathological changes in the reproductive organs of pregnant rabbits. The evaluation of embryotoxic and foetotoxic effects did not identify any differences between the foetuses of the animals assigned to different doses of thiozonide and the control group. The authors found no developmental abnormalities in the foetuses. Examinations of foetal skeleton development and internal organ condition identified no differences between the groups and no abnormalities. The authors registered the death of all foetuses (late resorption) in one rabbit from the 206 mg/kg group. Therefore, the 103 mg/kg dose (5 TDs) was selected as a reasonable No Observed Adverse Effect Level (NOAEL).Conclusions. Thiozonide has no embryotoxic, foetotoxic, or teratogenic effects.https://www.risksafety.ru/jour/article/view/362tuberculosisthiozonideantituberculosis medicinal productrabbitspregnancyembryotoxicityfoetotoxicityteratogenicity |
| spellingShingle | A. Yu. Borodina K. L. Kryshen A. Yu. Savchenko M. N. Makarova V. G. Makarov A Study of Embryotoxic, Foetotoxic, and Teratogenic Effects of the Original Antituberculosis Agent Thiozonide in Pregnant Rabbits Безопасность и риск фармакотерапии tuberculosis thiozonide antituberculosis medicinal product rabbits pregnancy embryotoxicity foetotoxicity teratogenicity |
| title | A Study of Embryotoxic, Foetotoxic, and Teratogenic Effects of the Original Antituberculosis Agent Thiozonide in Pregnant Rabbits |
| title_full | A Study of Embryotoxic, Foetotoxic, and Teratogenic Effects of the Original Antituberculosis Agent Thiozonide in Pregnant Rabbits |
| title_fullStr | A Study of Embryotoxic, Foetotoxic, and Teratogenic Effects of the Original Antituberculosis Agent Thiozonide in Pregnant Rabbits |
| title_full_unstemmed | A Study of Embryotoxic, Foetotoxic, and Teratogenic Effects of the Original Antituberculosis Agent Thiozonide in Pregnant Rabbits |
| title_short | A Study of Embryotoxic, Foetotoxic, and Teratogenic Effects of the Original Antituberculosis Agent Thiozonide in Pregnant Rabbits |
| title_sort | study of embryotoxic foetotoxic and teratogenic effects of the original antituberculosis agent thiozonide in pregnant rabbits |
| topic | tuberculosis thiozonide antituberculosis medicinal product rabbits pregnancy embryotoxicity foetotoxicity teratogenicity |
| url | https://www.risksafety.ru/jour/article/view/362 |
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