Dynamics of ultrastructural changes in glial cells and nerve fibers of the optic nerve of rats after intra-abdominal injection of a mixture of 40% Ethanol solution and 100% Methanol
Abstract
There are, quite often, cases of poisoning of human population with poor-quality alcoholic drinks, which include methanol. The optic nerve, retina and brain tissues are initially affected. A long-term study aimed at identifying initial structural changes in the visual analyzer in the application of various doses of methanol and its mixture with ethanol was carried out. Purpose: to study the dynamics of ultrastructural changes in glial cells and nerve fibers of the optic nerve, which are caused by mixture of ethanol 40% and methanol 100% in a ratio of 3:1 with a dose of methanol of 0.75 g/kg of rat weight. We examined the ultrastructure of the orbit part of the optic nerve of 43 adult rats (Wistar line) in the period from 3 hours to 14 days after one-time intra-abdominal injection of ethanol 40% and methanol 100%, 100% methanol, the dose of methanol is 0.75 g/kg of rat weight. In rats, LD50 is 9.5 g/kg of their weight. It was found out, that within 3 hours after the injection of the mixture of alcohols, the myelin sheath of large-caliber nerve fibers exfoliated, the axoplasm swelled and the mitochondria in their axons pathologically changed, the mitochondria altered in glial cells, which influenced the quality of nerve impulses and axoplasmic transport of substances. In the dynamics of the study, alterative changes in structures of the optic nerve progressed with the complete destruction of part of glial cells by 7 days, mainly in the first 3 days. After the use of methanol 100%, changes in structures of the optic nerve were similar to changes in them after the use of a mixture of alcohols, but with more significant pathology at all periods of observation with the peak of their manifestation on the 7th day. In glial cells and axons of nerve fibers from the 1st day of the study, signs of compensatory and restorative processes were found: they increased protein-synthesizing and energy-forming functions that were aimed at restoring the damaged ultrastructure. It is established, that 3 hours after the injection of a mixture of alcohols, reactive changes in the structures of the optic nerve of rats took place, which from the 1st day develop into pathological changes and are observed up to 14 days with the peak of their activity on the 7th day of the study. After the use of methanol 100%, the ultrastructure of the optic nerve of rats is more damaged than after the injection of a mixture of alcohols. It is proved, that methanol has a leading place in the development of pathological changes in structures of the optic nerve after the injection of a mixture of alcohols.
References
[2] Aisa, T.M., Ballut, O.M., & Ballut, E.М. (2016). Methanol intoxication with cerebral hemorrhage. Neurosciences (Riyadh), 21(3), 275-277. doi: 10.17712/nsj.2016.3.20150592
[3] Arun, S., Liu, L., & Donmez, G. (2016). Mitochondrial biology and neurological diseases. Curr. Neuropharmacol., 14(2), 143-154. doi: 10.2174/1570159X13666150703154541
[4] Bouskila, J., Palmour, R.M., Bouchard, J.F., & Ptito, M. (2018). Retinal structure and function in monkeys with fetal alcohol exposure. Exp. Eye Res., 177, 55-64. doi.org/10.1016/j.exer.2018.07.027
[5] Duarte, F., Amorim, J.A., Palmeira. C.M., & Rolo. A.P (2015). Regulation of mitochondrial function and its impact in metabolic stress. Curr. Med. Chem., 22(20), 2468-2479. doi: 10.2174/0929867322666150514095910
[6] Dumbrova, N.E., & Molchanyuk, N.I. (2010). Ультраструктурные изменения элементов зрительного нерва крыс в динамике после действия метанолу [Ultrastructural changes of rat optic nerve elements in the dynamics after the action of methanol]. Офтальм. журнал – Ophthalm. J., 2, 64-66.
[7] Icel, E., Suleyman, H., Yazici, G.N., Bakan, N., & Sunar, M. (2020). Effects of adenosinetriphosphate on methanol-induced experimental optic nerve damage in rats: biochemical and histopathological evaluation. Cutan. Ocul. Toxicol., 39(3), 244-248. doi: 10.1080/15569527.2020.1778017
[8] Galvez-Ruiz, A., Elkhamary, S.M., Asghar, N., & Bosley, T.M. (2015). Cupping of the optic disk after methanol poisoning. Br. J. Ophthalmol., 99(9), 1220-3. doi: 10.1136/bjophthalmol-2014-306354
[9] Golovenko, N.Ya., Larionov, V.B., Ovcharenko, N.V., Borisyuk, I.Yu., & Lihota, E.B. (2008). Токсикокинетическое взаимодействие этилового и метилового спиртов в организме белых мышей [Toxicokinetic interaction of ethanol and methanol in organism of white mice]. Cовременные проблемы токсикологии – Modern Problems of Toxicology, (1), 32-36.
[10] Kenneth, Mc M., Dag, J., & Knut, E.H. (2016). Antidotes for poisoning by alcohols that form toxic metabolites. Br. J. Clin. Pharmacol., 81(3), 505-515. doi: 10.1111/bcp.12824
[11] Kursov, S.V., Mykhnevych, K.H., & Kryvobok, V.Y. (2012). Острое отравление етанолом [Acute ethanol poisoning]. Медицина неотложного состояния – Medical Emergency, (7-8), 22-35.
[12] Manuchehri, A.A., Alijanpourm E., Daghmechi, M., Ghaeminan, N., Abedi, S.H., Nikbakhsh, N. … Amani, N. (2015). A case of methanol poisoning leading to prolonged respirator dependency with consequent blindness and irreversible brain damage. Caspian Journal of Internal Medicine, 6(3), 180-183. PMCID: PMC4650797
[13] Molchanіuk, N.I. (2015). Свето- и электронно-микроскопическое изучение хориокапилляров, пигментного эпителия и фоторецепторных клеток сетчатки крыс в динамике после введения различных доз метанолу [Light- and electron-microscopic study of choriocapillaries, pigment epithelium and photoreceptor cells of the retina of rats in dynamics after administration of various doses of methanol] Вісник Київського національного університету імені Тараса Шевченка. Проблеми регуляції фізіологічних функцій – Bulletin of Kiev National Taras Shevchenko University. Problems of regulation of physiological functions, 18(1), 74-78.
[14] Mojica, C.V., Pasol, E.A., Dizon, M.L., Kiat, W.A., Tru, L., Dominguez, J.C. … Tuaño, B.J. (2020). Chronic methanol toxicity through topical and inhalational routes presenting as vision loss and restricted diffusion of the optic nerves on MRI: A case report and literature review. еNeurological Sci., 20, 100258. doi: 10.1016/j.ensci.2020.100258
[15] Pohanka, M. (2016). Toxicology аnd the biological role оf methanol аnd ethanol: Current View. Biomed. Pap. Med. Fac. Univ. Palacky Olomouc. Czech. Repub., 160(1), 54-63. doi.org/10.5507/bp.2015.023
[16] Rasheed, R.A., Youakim, M.F., & Yehia, M.A. (2017). Possible protective effect of ethanol on acute methanol intoxicated retina in rats: A histological and ultrastructural study. Protection of Intocxicated Retina, 1(2), 146-153. doi: 10.21608/jmh.2018.1795.1026hia3
[17] Ran, M., Li, Y., Zhang, L., Wu, W., Lin, J., Liu, Q, & Ou, S. (2019). Clinical features, treatment, and prognosis of acute methanol poisoning: experiences in an outbreak. Int. J. Clin. Exp. Med., 12(5), 5938-5950. ISSN: 1940-5901/IJCEM0085245
[18] Sayit, A.T., Aslan, K., Elmali, М., & Gungor, I. (2016). Methanol-induced toxic optic neuropathy with diffusion weighted MRI findings. Cutan. Ocul. Toxicol. Dec., 35(4), 337-340. doi: 10.3109/15569527.2015.1122031
[19] Setiohadji, B., Irfani, I., Rifada, M., Virgana, R., & Kartasasmita, A.S. (2018). The Superoxide Dismutase Mimetic Tempol and Its Effect on Retinal Ganglion Cells in Experimental Methanol-Intoxicated Rats. Ophthalmol. Ther., 7(1), 167-172. doi: 10.1007/s40123-018-0132-z
[20] Shaughnessy, D.T., McAllister, K., Worth, L., Haugen, A.C., Meyer, J.N, Domann, F.E. … Tysonet, F.L. (2014). Mitochondria, energetics, epigenetics, and cellular responses to stress. Environ. Health Perspect., 122(12), 1271-1278. doi: 10.1289/ehp.1408418
[21] Shin, Y.W., & Uhm, K.B. (2011). Case of Optic Nerve Atrophy with Severe Disc Cupping after Methanol Poisoning. Korean J. Ophthalmol., 25(2), 146-150. doi: 10.3341/kjo.2011.25.2.146
[22] Taşlı, N.G., Çimen, F.K., Karakurt, Y., Uçak, T., Mammadov, R., Süleyman, B., & Süleyman, H. (2018). Protective effects of Rutin against methanol induced acute toxic optic neuropathy: an experimental study. Int. J. Ophthalmol., 11(5), 780-785. doi: 10.18240/ijo.2018.05.10
[23] Tsymbalyuk, V.I., Nosov, A.T., Chebotareva, L.L., & Vasyuta, V.A. (2004). Електрофізіологічні та морфологічні показники стану зорового аналізатора в динаміці застосування трофіну при інтоксикації метанолом [Electrophysiological and morphological exponents of the visual analyzer condition in the dynamics of the visual Trophin application in the methanol intoxication]. Український нейрохірургічний журнал – Ukrainian Neurosurgical Journal, (3), 97-102.
[24] Vaneckova, S., Zakharov, J., Klempir, Růžička, E., & Vaneckova, M. (2015). Imaging findings after methanol intoxication (cohort of 46 patients). Neuro Endocrinol. Lett., 36(8), 737-744. PMID: 26921573.
[25] Zabrodsky, P.F., & Serov, V.V. (2013). Иммунотоксикологическая характеристика метанола. Коррекция нарушений функций иммунной системы. [Immunotoxicological Сharacteristics of Methanol. Correction of Immune System Disorders]. Саратов. – Saratov.
[26] Zabrodsky, P.F., & Germanchuk, V.G. (2001). Влияние этанола на изменение иммунотоксичности метанола [The effect of ethanol on the change in the immunotoxicity of methanol]. Эксперим. и клин. фармакол. – Experim. and Clin. Pharmacol., 64(5), 40-42.
[27] Zakharov, S., Pelclova, D., Diblik, P., Urban, P., Kuthan, P., Nurieva, O. … Hovdaet, K.E. (2015). Long-term visual damage after acute methanol poisonings: longitudinal cross-sectional study in 50 patients. Clinical Toxicology, 53(9), 884-892. doi: 10.3109/15563650.2015.1086488
[28] Zyoud S.H., Al-Jabi S.W., Sweileh W.M., Awang R., & Waring W.S. (2015). Bibliometric profile of the global scientific research on methanol poisoning (1902-2012). J. Occup. Med. Toxicol., 10(17), 1-8. doi: 10.1186/s12995-015-0062-9
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