HIF-1α as a Target Molecule in the Use of Triazino-Indole Derivative on the Acoustic Trauma Model

Audiology Research

Leonid G. Buynov¹  Vladimir V. Dvorianchikov²  Maksim S. Kuznetsov²  Lev A. Glaznikov²  Aleksandr L. Pastushenkov³  Vladimir L. Pastushenkov⁴ 

[1] Department of Medical and Valeological Disciplines, The Herzen State Pedagogical University of Russia, 191015 St. Petersburg, Russia;Department of Otorhinolaryngology, Military Medical Academy, 191015 St. Petersburg, Russia;Department of Pharmacy and Pharmacology, North-Western State Medical University Named after I.I. Mechnikov, 191015 St. Petersburg, Russia;LLC “Farm-Trisan”, 191015 St. Petersburg, Russia;

关键词: hypoxia;    hypoxia-inducible factor;    HIF-1α;    acoustic trauma;    antihypoxants;    triazino-indole;   

DOI  :  10.3390/audiolres11030034

来源: DOAJ

【 摘 要 】

The effect of triazino-indole derivative (Trisan) on hypoxia-inducible factor (HIF) expression level in the organ of Corti, when administering it for therapeutic and preventive purposes, was investigated using an acoustic trauma model in experimental animals (female F1 hybrids of CBA and C57BL/6 lines). Cytoflavin was used as a comparator product. Study product Trisan (1% solution) was injected intravenously, intramuscularly and intraperitoneally, in the dose of 5, 7 and 10 mg/kg 2 h after the acoustic trauma for therapeutic purposes and in the dose of 5, 7 and 10 mg/kg for 3 days before the acoustic trauma for preventive purposes. IHC methods were used to investigate the organ of Corti. Trisan was observed to increase HIF expression in hair cells and neurons of the spiral ganglion in case of acoustic trauma. Depending on the dose, the increased HIF-1 expression in hair cells and spiral ganglion occurred both after therapeutic and preventive use of Trisan. Maximum HIF expression in hair cells and ganglion was noted at the therapeutic and preventive drug dose of 10 mg/kg. Following experimental results, we conclude that the otoprotective effect of triazino-indole derivative is realized via its effect on HIF metabolism, which makes it a target molecule for the drug.

【 授权许可】

Unknown