Abstract
Up to 60 % of patients suffer from the neurotoxicity of the chemotherapy drug Paclitaxel, namely paclitaxel-induced peripheral neuropathy (PIPN), during the treatment of breast cancer, ovarian cancer, and non-small cell lung cancer. Of these, up to 25 % of patients require modification of the paclitaxel treatment regimen, including dose reduction, delay, or discontinuation of therapy. Previous attempts to use neuroprotective agents in humans and in animal models have not shown sufficient efficacy in preventing or significantly reducing the manifestations of PIPN. The aim of our study was to study the effect of the neuroprotective agent 2-ethyl-6-methyl-3-hydroxypyridine succinate (HS) on the morpho-functional parameters of the sciatic nerve and its segmental centers in experimental PIPN. In the experiment, 56 white rats were used, which were injected intraperitoneally with Paclitaxel at a dose of 2 mg/kg of body weight 4 times after one day, after which the animals were divided into an experimental group – 24 animals that were injected with HS and a control group (24 animals, injection of water for injections). The method of studying mechanical allodynia was von Frey monofilaments, thermal hyperalgesia was studied by the hot plate test, and the electron microscopic examination was carried out according to generally accepted methods and studied with the help of a PEM-125 K electron microscope. The results of the hot plate test and the use of von Frey monofilaments showed that the use of HS reliably reduces manifestations of PIPN on the 7th, 14th and 28th days of the experiment. In rats treated with HS, destructive-dystrophic phenomena in the myelin nerve fibers of the sciatic nerve are less pronounced, and in individual fibers in the axon, phenomena of incomplete splitting of mitochondria with the formation of vacuoles filled with medium electron density contents are observed, and small young mitochondria are also visualized. During the first 28 days, we noted less pronounced destructive-dystrophic changes in the neurons of the spinal cord nodes, namely: chromatolysis of light and dark neurons and swelling of their cytoplasm, phenomena of neuronophagy in gliocytes, hypertrophy of certain areas of the myelin sheath. The results of the electron microscopic study are fully consistent with the data of neurophysiological studies and indicate the possibility of using HS as an effective neuroprotector in PIPN.
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