Експериментальне вивчення впливу адеметіоніну на активність щурів з енцефалопатією, що обумовлена впливом протитуберкульозних препаратів

Abstract

Було досліджено вплив протитуберкульозних препаратів (ПТП), які складають схему лікування хіміорезистентного туберкульозу на рухову і пошукову активність щурів у “відкритому полі”, та можливості корекції порушень що виникли за допомогою адеметионину (гептралу). Під час дослідження встановлено, що тривале введення зазначеної комбінації ПТП, призводить до розвитку токсичної енцефалопатії у експериментальних тварин, що проявляється зниженням загальної і пошукової активності та розвитком тривожної поведінки. Введення адеметіоніну (гептралу) паралельно із комбінацією ПТП, запобігає розвитку токсичної енцефалопатії у експериментальних тварин, що є експериментальним обґрунтуванням застосування гептрала при проведенні п’ятикомпонентної терапії хіміорезистентного туберкульозу в якості нейропротек-тивного засобу. Treatment of MDR-TB - lasts long and accompanied by numerous toxic adverse drug reaction (ADR), leading to treatment failure, and non-compliance of patients. Therefore, it is necessary to search for universal drugs with both neuro- and hepatoprotective properties that could have therapeutic effect in the majority of toxic ADR of antimycobacterial therapy (AMBT). As such a promising medicine could be considered - ademetionin (heptral). Object and methods. 30 healthy Wistar line rats, 6 months age, weighing 220-290 g contained in standard conditions (12-hour light cycle, at 220C° temperature). The animals were divided into 3 groups of 10 animals in each: Group I - received intragastric probe of 1% starch mucus in the volume of 5 ml, and intramuscular injection - saline; group II - obtained drugs for the treatment of resistant forms of tuberculosis (TB Drugs) (pyrazinamide 300 mg/kg, Ethionamidum 150 mg/kg, cycloserine 150 mg/kg, levofloxacin 200 mg/kg and intramuscularly - kanamycin 200 mg/kg) through intragastric probe; III - in the background of TB Drugs in similar doses (as in the second group) received geptral at a dose of 250 mg/kg intragastric. Drugs were administered in 1% starch mucus in the amount of 5 ml - every night at 10:00, within 90 days. Definition of motor and search activity the was conducted using the technique “open field” using arena - 80x80x35 sm. Results and discussion. It was established that the administration of TB drugs led to a significant decrease of total activity of animals in the group II (25.4%). In the group with Heptral (group III), this indicator had tendency to increase (on 11.6%, p = 0.599). In the group II (TB drugs only), observed a reliable reduction in the duration of high activity (by 42.0%) and low activity (by 20.7%) and tendency to reduce the amount of fading (by 14,1%, p = 0.678), but with increase in their duration (length of inactivity in this group was reliable increased by 52.6% in comparison with the control group). The duration of high and low activity in the group III had no reliable difference with indicators of I (control) group, but the duration and amount of inactivity fading reliable decreased (by 55.0% and 43.7%, respectively). Thus application TB drugs only and their use in combination with Heptral, led to a reliable increase in the traveled distance during the experiment (by 32.1% and 59.2%, respectively) compared with the control group. Animals in I (control) group and group II traveled a shorter distance in the center of the arena compared to the group III (by 7 times and 4.3 times, respectively, p <0.05). Avoiding the center of the arena, and more compared to the group III number and duration of fading testifies for the development of disturbing behavior in animals from I and II groups. Reliable increase in vertical search activity, with an increase in overall activity could indicate about increasing of anxiety and emotion of animals of group III.