Acute, subchronic oral toxicity, toxicokinetics, and genotoxicity studies of DFC-2, an antitubercular drug candidate
| Autor: | Hoonhee Seo, Sukyung Kim, Imtiazul Islam, Kee-In Lee, Hafij Al Mahmud, Ho-Yeon Song, Young Sig Gil |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Drug Tuberculosis media_common.quotation_subject 030231 tropical medicine Antitubercular Agents Pharmacology Toxicology medicine.disease_cause Rats Sprague-Dawley Mycobacterium tuberculosis 03 medical and health sciences 0302 clinical medicine In vivo Toxicity Tests Acute medicine Animals Toxicokinetics media_common Mice Inbred ICR No-Observed-Adverse-Effect Level biology Mutagenicity Tests business.industry Toxicity Tests Subchronic General Medicine medicine.disease biology.organism_classification 030104 developmental biology Toxicity Female Micronucleus business Genotoxicity |
| Zdroj: | Regulatory Toxicology and Pharmacology. 95:91-101 |
| ISSN: | 0273-2300 |
| DOI: | 10.1016/j.yrtph.2018.02.011 |
| Popis: | The infectious disease tuberculosis remains a serious global health issue and is responsible for nearly 1.8 million deaths every year. In our previous study, DFC-2 was confirmed to show anti-tubercular activity against drug-susceptible and drug-resistant strains of Mycobacterium tuberculosis. To support the safety-in-use of DFC-2 as an anti-tubercular drug, DFC-2 was tested via single- and 28-day repeated-dose oral toxicity study and mutagenicity assays. In the oral toxicity study, a single oral dose of DFC-2 at 2000 mg/kg did not produce deaths or abnormal lesions in the internal organs of rats. The results of a 28-day orally repeated dose of DFC-2 did not show treatment-related deaths or obvious toxicity symptoms in the animals treated with a dose of 300 mg/kg/day during the experimental period. Therefore, the no-observed-adverse-effect level (NOAEL) of DFC-2 was determined as 300 mg/kg/day for both male and female rats. In addition, DFC-2 showed no genetic toxicity in in vitro bacterial reverse mutation test, in vitro chromosomal aberration test, and in vivo mouse bone marrow micronucleus formation test. These results indicate that DFC-2 is a promising anti-tubercular drug candidate with a favorable safety profile. |
| Databáze: | OpenAIRE |
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