ISSN 2415-3060 (print), ISSN 2522-4972 (online)
  • 10 of 60
JMBS 2019, 4(6): 74–79
Experimental Medicine and Morphology

Morpho-Functional State of the Spinal Nodes in Paclitaksel-Induced Neuropathy Corrected by Armadin

Ostrovskyi M. M.

The purpose of this study was to study the fine structure of neurons of the spinal cord with correction of paclitaxel-induced neuropathy by Armadine. Material and methods. In the experiment 80 white rats were intraperitoneally injected with paclitaxel (Actavis, Romania) at a dose of 2 mg/kg 4 times every other day (summary dose – 8 mg/kg). It was followed with intraperitoneal administration of Armadine at a dose of 10 mg / kg to 48 animals (at controls 32 rats received intraperitoneal water for injection). Observation periods were the 1st, 7th, 14th, 21st, 28th days. Results and discussion. In the dynamics of observation during the first week of experiment neurons of spinal nodes began to develop restorative processes on the background of the damage as a result of the neuropathy: swelling of the cytoplasm, chromatolysis of the basophilic substance, vacuolation of mitochondria, shortening of their combs. Hypertrophy of individual sections of the myelin sheath, with stratification and separation of myelin plates were clearly visible in the myelin nerve fibers of the posterior spinal cord deformation. We identified vacuolated mitochondria, disorganized microtubules and microfilaments, autophagosomes, and edema in the axoplasm of the axial cylinders. On the 14th-21st days, the neurons in the hyaloplasm were almost transparent and the ribosomes and polyribosomes were identified. Organelles exhibited mitochondria of different sizes in different morpho-functional states; most of them were characterized by a complete outer mitochondrial membrane and short combs of the inner membrane. In the peripheral areas of the neuroplasma were the sites of small-focal chromatolysis. Separate myelin nerve fibers of the posterior spinal cord were deformed, without gross violations of the lamellar structure, the myelin sheath was preserved, and single mitochondria in the axial cylinder, microfilaments and microtubules were disordered. The characteristic feature in neurons on the 28th day was the presence of branched mitochondria of normal structure and among them small sizes, calves of basophilic substance of different sizes. In other neurons, there was a moderate compaction of the hyaloplasm with numerous ribosomes and polyribosomes, a hypertrophied Golgi complex, and no vacuoles. Myelin nerve fibers of the posterior roots became rounded, in the myelin sheath myelin plates formed compact layers. In axoplasm of axial cylinders, mitochondria had short combs. The microfilaments and microtubules were oriented longitudinally, evenly and orderly. Conclusion. Thus, we found out that Armadine had a positive, correcting effect on the morpho-functional state of neurons of the rat cerebrospinal cord after modeling paclitaxel-induced neuropathy, which was manifested by high regenerative capacity of mitochondria and led to the normalization of the structure of neurons and nerves.

Keywords: Paclitaxel, cerebrospinal cord, neurons, Armadine

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  1. Volchehorskyi YA, Moskvycheva MH. Vlyianye preparata meksydol na proiavlenyia dystalnoi symmetrychnoi polynevropatyy u bolnikh sakharnim dyabetom s syndromom dyabetycheskoi stopy. Farmateka. 2007; 20(154): 76-9. [Russian]
  2. Dronov SN. Farmakolohyia meksydola y eho prymenenye v psykhonevrolohycheskoi praktyke. Visnyk VDNZU «Ukrainska medychna stomatolohichna akademiia». 2016; 3(51): 328-35. [Russian]
  3. Skopyn P. Vlyianye meksydola na antymetastatycheskuiu aktyvnost protyvoopukholevikh preparatov. Aspyrantskyi vestnyk Povolzhia. 2009; 3-4: 104-6. [Russian]
  4. Carvalho LF, Silva AMF, Carvalho AA. The use of antioxidant agents for chemotherapy-induced peripheral neuropathy treatment in animal models. Clin Exp Pharmacol Physiol. 2017; 44(10): 971-9.
  5. Dougherty PM, Cata JP, Cordella JV, Burton A, Weng HR. Taxol-induced sensory disturbance is characterized by preferential impairment of myelinated fiber function in cancer patients. Pain. 2004; 109(1-2):132–42.
  6. Duggett NA, Griffiths LA, Flatters SJL. Paclitaxel-induced painful neuropathy is associated with changes in mitochondrial bioenergetics, glycolysis, and an energy deficit in dorsal root ganglia neurons. Pain. 2017; 158(8): 1499-508.
  7. Hidaka T, Shima T, Nagira K, Ieki M, Nakamura T, Aono Y, et al. Herbal medicine Shakuyaku-kanzo – to reduces paclitaxel-induced painful peripheral neuropathy in mice. Eur J Pain. 2009; 13(1): 22–7.
  8. Gauchan P, Andoh T, Ikeda K, Fujita M, Sasaki A, Kato A, et al. Mechanical allodynia induced by paclitaxel, oxaliplatin and vincristine: different effectiveness of gabapentin and different expression of voltage-dependent calcium channel alpha(2)delta-1 subunit. Biol Pharm Bull. 2009; 32 (4): 732–4.
  9. Peters CM, Jimenez-Andrade JM, Kuskowski MA, Ghilardi JR, Mantyh PW. An evolving cellular pathology occurs in dorsal root ganglia, peripheral nerve and spinal cord following intravenous administrtion of paclitaxel in the rat. Brain Res. 2007; 1168: 46–59.
  10. Polomano RC, Mannes FJ, Clark US, Bennett GJ. A painful peripheral neuropathy in the rat prodiced by the chemotherapeutic drug, Paclitaxel. Pain. 2001; 94(3): 293-304.
  11. Wozniak KM, Nomoto R, Lapidus RG, Wu Y, Carozzi V, Cavaletti G, et al. Comparison of neuropathy-inducing effects of eribulin mesylate, paclitaxel, and ixabepilone in mice. Cancer Res. 2011; 71(11): 3952–62.