Thermoregulatory effects of triiodothyronine derivatives: in vivo study and review of potential neuroprotective effects

Background. According to the results of several clinical and experimental studies, transient hypothermia is a promising neuroprotection method for ischemic stroke. However, existing methods for inducing hypothermia (both physical and pharmacological) have a significant amount of undesirable vascular, metabolic and endocrine side-effects. In recent years, more and more attention has been paid to new hypothermia inducers, some of which are derivatives of thyroid hormones. The study aimed to investigate the effect of the synthetic analogue of thyronamine T(0)AM on the change in rectal temperature in white laboratory rats using inhaled anaesthesia. Materials and methods. The study was performed on 12 white out-breed laboratory rats, divided into experimental and control groups. Animals of the control group were injected intraperitoneally with 2 ml of water for injection, animals of the experimental group were injected with a synthetic analogue of T(0)AM at a concentration of 50 mg/kg dissolved in 2 ml of water for injection. Then, in animals of all groups, rectal temperature was measured for 30 minutes under halothane inhaled anaesthesia with an interval of 3 minutes. Also, the temperature was measured once after 60 minutes after administration of the drug in awakened rats. Statistical processing of the obtained data was performed using Microsoft Office Excel 2007 and MedCalc 14.1. To compare differences between the groups, the t-test for independent samples and the ANOVA test were used. The Wilcoxon test was used to compare temperature data before and after administration of the synthetic thyronamine analogue. Results. Cryogenic effect of a synthetic analogue of the thyronamine deiodinated form T(0)AM was described. It was shown that intraperitoneal administration of 50 mg/kg T(0)AM analogue to laboratory rats led to a rapid reversible decrease in body temperature by an average of 2.5 °C (95% CI 2.2–2.8° C). The action of a synthetic analogue of thyronamine, independent of another hypothermia inducer (halothane), has been demonstrated. In a literature review focused on neuroprotection, an attempt was made to identify the mechanisms of hypothermic action of thyronamine and to substantiate the choice of directions for further clinical and experimental studies. Conclusions. The data obtained confirm the influence of the thyronamine T(0)AM synthetic analogue on the processes of thermogenesis, while the observed hypothermic effects of thyronamine could not be explained by the action of inhaled anaesthesia. The pattern of body temperature lowering in the experimental group indicates a different from halothane cryogenic action of thyronamine derivates.