EFFECTIVENESS OF L-CARNITINE IN COMPENSATION OF ELECTROPHYSIOLOGICAL MANIFESTATIONS OF DEXAMETHASONE-INDUCED MYOPATHY IN EXPERIMENTS ON ANIMALS

The effectiveness of moderate therapeutic doses of L-carnitine (L-CAR, 100 mg/kg/day, intraperitoneally) to compensate for the negative effects of long-term administration of dexamethasone (DM, 0.25 mg/kg/2 days, intraperitoneally, for 10 to 60 days) on skeletal muscle of mixed type with predominantly glycolytic fibers (m. tibial anterior) was studied in mature female rats.

The preparations were administered to the animals of the experimental groups for 10 (10DM-, 10L-CAR-, and 10DM+L-CAR-groups), 30 (30DM-, 30L-CAR-, and 30DM+L-CAR-groups) and 60 (60DM, 60L-CAR, and 60DM+L-CAR groups) days at doses equivalent to moderate therapeutic doses for humans, intraperitoneally: L-carnitine at a dose of 100 mg/kg/day, DM at a dose of 0.25 mg/kg, once every 2 days.

The administration of L-carnitine in combination with dexamethasone prevented the development of signs of myopathic changes typical for the DM-groups: a decrease in muscle mass and the number of its activated motor units, a decrease in the amplitude of M-responses against the background of their polyphasia. In 30–60 % of individuals receiving dexamethasone with L-carnitine, a marked facilitation of synaptic transmission was observed at the optimal frequency (30 imp/s) of stimulation of the neuromuscular apparatus against the background of not reduced, as in the animals of the DM-group, but normal and even increased amplitude of M-responses (by 94–59 % after 10 and 60 days of administration of the pair of medicines, p<0.05 relative to the control). In addition, for animals of the DM+L-CAR-groups, a much more significant post-tetanic facilitation was not characteristic than in the control against the background of a reduced amplitude of the 1st M-response in the series, typical for the DM-groups. All these facts indicate in favor of the absence of the initial blockade of synapses typical for the DM-groups with the complex use of dexamethasone with L-carnitine.

The use of L-carnitine in combination with dexamethasone somewhat reduced the incidence of pathologically significant depression of synaptic transmission at the optimal stimulation frequency (30 imp/s) of the neuromuscular apparatus: this depression occurred in 20 % of individuals only in the 30DM+L-CAR-group, whereas with isolated use of dexamethasone it was recorded in all DM-groups with a frequency of 20–30 %. At the same time, after 30 and 60 days of combined use of dexamethasone with L-carnitine, a more pronounced decrease in the amplitude of M-responses during high-frequency stimulation (70 imp/s) of the peroneal nerve relative to the initial level was observed compared to the control (p<0.05), indicating a decrease in synaptic lability. In the case of subchronic combined use of dexamethasone with L-carnitine (after 30–60 days), 50–30 % of individuals showed reduced reliability of synaptic transmission during low-frequency stimulation (4 imp/s) of the neuromuscular apparatus. This fact, against the background of signs of reduced synaptic lability, but the absence of signs of their initial blocking, indicates postsynaptic disorders in animals subchronically receiving dexamethasone with L-carnitine.

L-carnitine at a dose of 100 mg/kg/day, equivalent to a moderate therapeutic dose for humans (1.5 g/day), in model experiments on animals showed a fairly high efficiency in compensating for the electrophysiological manifestations of dexamethasone-induced myopathy.