The Effect of 2-Ethyl-6-Methyl-3-Hydrooxypyridine Succinate in Correcting Paclitaxel-Induced Retinopathy

In the run of experiment 72 white rats received intraperitoneal injections of Paclitaxel (Actavis, Romania) dosed 2 mg/kg of body weight, 4 times every 24 hours; the total dosage equaled 8 mg/kg. The following step was to inject 48 animals with 2-ethyl-6-methyl-3-hydrooxypyridine succinate (Armadin) at the dosage of 10 mg/kg of body weight (the control group of animals received intraperitoneal injections of water for injection). We have found out that the Armadin correction of Paclitaxel-induced retinopathy improves the morphometric indexes (the thickness of layers and retina) from the 1st to the 28th day: the layer of rods and cones is renovated; other layers are close to norm indexes. On the first day after the terminaton of Armadin injections the layer of rods and cones has even thickness and has become thicker up to (16,97±0,24) mkm, while in the control group the layer in question was (10,15±0,15) mkm, р<0,05 thick. In 7 days time the layer thickness grew to be (20,01±0,13) mkm versus the thickness in the control group, which was (9,81±0,09) mkm, р<0,05. The thickness of retina increased to (137,11±0,69) mkm, while it decreased in the control group. On the 15th and the 21st days the changes towards stabilizing and normalizing of the morpho-functional state of retina, especially in the layer of rods and cones, whose thickness grew to (21,30±0,27) mkm and (24,60±0,35) mkm. The thickness of the outer nuclear layer was (39,76±0,41) mkm and (40,01±0,53) mkm; the inner nuclear layer became (20,47±0,23) mkm and (20,24±0,57) mkm; ganglionic layer equaled to до (10,11±0,19) mkm and (8,16±0,37) mkm. These indexes were close to norm. On the 28th day the general tendency of changes was not so unanimous as before. The thickness indexes differed consistently from norm. The retina thickness dropped to (131,53±0,18) mkm, while in the control group it was (116,26±0,92), and the norm was (125,01±0,15) mkm. To positive changes we may refer the orderly location of the outer segments of rods and cones; the roundness of nuclei in two- and multipolar neurons; the outer plexiform layer contained horizontal neurons, and the inner plexiform layer contained amacrine cells. We also observed more capillaries in the inner retinal plexus between ganglionic and optic fiber layers. Starting from Day 60 the positive effect of Armadin decreases, the retina layer morhometric indexes, except for the inner and outer plexiform layers, get thinner both in the experiment and in the control group. On Day 120 the inner and outer nuclear layers as well as the optic fiber layer reveal the signs of swelling. The retina thickness grows. The morphological changes discovered may be caused by the pharmacological properties of Armadin, namely, the inhibition of free radical processes, protection of membranes, antihypoxic effect, improvement of blood microcirculation and its rheological properties. The results obtained in the run of the experiment confirm that Armadin (syn. Mexidol) contributes to preserving ganglionic cells of the retina and optic nerve fibers in progressing neuropathy whose results would be chronic ischemia and hypoxia. Applying Armadin in Paclitaxel-containing chemotherapies may help preserve the functions of retina and optic nerve, which requires further research.