Uridine increases endurance and improves the rehabilitation of experimental animals after physical performance

BACKGROUND: The pharmacological correction of metabolic processes, providing an increase in the efficiency and duration of physical performance and contributing to rapid rehabilitation, is an important component of the regulation of adaptation. Previously, we found that the pyrimidine nucleoside uridine exhibits antihypoxic properties, activates mitochondrial K⁺_ATP channels (mitoK_ATP), normalizes energy metabolism, reduces lipid peroxidation, activates the antioxidant system, and increases glycogen content. The substance with such properties was assumed to increase endurance and improve recovery after physical performance.

AIM: To examine the effect of uridine on the endurance of experimental animals in the forced swimming test under different intensities of physical performance and their rehabilitation.

MATERIALS AND METHODS: Experiments were performed on male Wistar rats (350–380 g) and male outbred mice (25–30 g). In the first series, the effect of uridine on the rat’s endurance was studied in the forced swimming test with a load of 5%, 7%, or 10% of the animal weight. In the second series, the effect of uridine on the first phase of recovery was evaluated in a three-load swimming test. Mice with 10% load were subjected to a swimming test three times, after which the trail index —the ratio of time of the third trail to the first trail — was determined. The frequency of animals with low, medium, and high recovery ability was estimated. Uridine 30 mg/kg or physiological saline (control) was administered 30 min before testing, 5-hydroxidecanoate (5-HD, mitoK_ATP blocker) 5 mg/kg 45 min before testing, and mexidol (reference drug) 200 mg/kg 50 min before testing.

RESULTS: Uridine increased the critical swimming duration by 58% and 44% at 5% and 7% exercise, respectively, in comparison with control. At 7% load, the drug increased the period before the appearance of the first signs of fatigue by 100%. After the blockade of mitoK_ATP channels, the effect of uridine decreased by 40% in the presence of fatigue and 24% in critical swimming duration. In the three-load swimming test, uridine increased the trail index by 1.5 times, which was comparable to the effect of mexidol, and increased the number of animals with a high ability to recover by 2.6 times. The use of uridine after mitoK_ATP channel blockade did not lead to a decrease of its positive effect and the blockade of channels with 5-HD did not affect rehabilitation.

CONCLUSIONS: Uridine increases the endurance of rats with a medium load in the forced swimming test and the rehabilitation of mice in the three-load swimming test. It also increases the number of animals with a high ability to recover after a swimming performance. The mechanism of its effects was realized both through the activation of mitoK_ATP channels and, probably, the stimulation of glycogenesis.