Objective of the study. To investigate the effect of triazino-indole derivative on the parameters of glycolysis in the endolymph during preventive and therapeutic use on the model of acoustic trauma. Experimental animals and methods. The experiments were carried out on 82 mice, female F1 hybrids of the CBA and C57BL/6 lines weighing at least 17 g at the age of 4–12 weeks. When simulating an acute acoustic trauma, an animal was exposed to white noise with a level of 107 dB SPL and frequency band 3–100,000 kHz. For therapeutic purposes, a single intravenous injection of a triazino-indole derivative was carried out immediately after noise exposure. The drug was administered at doses of 5, 7, and 10 mg/kg of animal weight. For prophylactic purposes, the intramuscular drug injection was administered before the acoustic trauma application. The drug was administered at doses of 5, 7, and 10 mg/kg of animal weight once a day for 3 days before noise exposure. The Cytoflavin was a reference drug. A normal saline was administered to the control group. When using the acoustic trauma models, the metabolic processes level in the cochlea was assessed by the glucose and lactic acid (lactate) content in the labyrinth fluid before and 2 hours after pathological exposure. Results and discussion. The triazino-indole derivative, both during preventive and therapeutic administration, significantly corrects changes in the glycolysis (glucose, lactate) indicators in the endolymph, thereby improving the bioenergetics of the inner ear cells. The best effect is observed when the drug is administered at a dose of 10 mg/kg. When compared with Cytoflavin, the antihypoxic effect of the triazino-indole derivative is more pronounced.

In the study on the model of acoustic trauma in experimental animals (mice), the otoprotective effect of the triazine-indole derivative was shown due to the influence on the expression level of hypoxia-inducible factor (HIF) in the Corti organ and spiral ganglion cells. For therapeutic purposes, the drug was administered as a 1% solution at a dosage of 5, 7, 10 mg/kg 2 hours after acoustic exposure. For preventive purposes, the drug was administered at a dosage of 5, 7, 10 mg/kg for 3 days before acoustic exposure. The comparator drug was Cytoflavin. The control group received a saline solution. The immunohistochemical study was carried out using an anti-mouse polymerized immunohistochemical imaging system and mouse monoclonal antibodies to HIF1. In immunohistochemical preparations scanned using a digital scanner, the HIF1-positive area (%) in the cochlea and spiral ganglion cells was calculated using a morphometric program. The color was evaluated by the average cytochemical coefficient. It was found that the severity of HIF expression depended on the dose of the administered drug and coincided with electrophysiological changes in experimental animals. The antisurditant effect of the triazine-indole derivative is realized by influencing the level of HIF expression, which allows it to be regarded as a target molecule when using the drug.