Abstract
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.
Highlights
In the modern world, the prevalence of noise-induced hearing loss has arguably reached epidemic proportions [1]
Treatment, 5 mg Trisan, prevention, 5 mg hypoxia-inducible factor (HIF) Expression Based on the Findings of Immunohistochemical
HoWangYin et al used human mesenchymal stem cells and observed inhibition of PHD2 enzyme which is involved in hydroxylation of HIF molecule what results in its proteolytic degradation
Summary
The prevalence of noise-induced hearing loss has arguably reached epidemic proportions [1]. Prior research has demonstrated that exposure to high levels of noise results in microcirculation disturbance in the internal ear and, subsequently, in hypoxia in the organ of Corti [2]. This results in accumulation of active oxygen and nitrogen forms, so-called oxidative stress and programmed and/or necrotic cell death [3]. Hypoxia resistance of hair cells in the organ of Corti is realized through the path associated with an HIF molecule [6] It was first identified and investigated by Gregg Semenza and researchers from the Johns Hopkins University in Baltimore in 1992 [7]. They were awarded a Nobel Prize for physiology and medicine for their studies in 2019
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