Russian Journal of Biological Physics and Chemisrty Russian Journal of Biological Physics and Chemisrty АКТУАЛЬНЫЕ ВОПРОСЫ БИОЛОГИЧЕСКОЙ ФИЗИКИ И ХИМИИ 2499-9962 83371 10.29039/rusjbpc.2023.0628 МЕДИЦИНСКАЯ БИОФИЗИКА И БИОФИЗИЧЕСКАЯ ХИМИЯ MEDICAL BIOPHYSICS AND BIOPHYSICAL CHEMISTRY МЕДИЦИНСКАЯ БИОФИЗИКА И БИОФИЗИЧЕСКАЯ ХИМИЯ NON-STEROID ANTI-INFLAMMATORY DRUG MELOXICAM ATTENUATES THE EFFECT OF IMMUNOMODULATOR GLUTOXIM ON Na+ TRANSPORT IN FROG SKIN EPITHELIUM НЕСТЕРОИДНЫЙ ПРОТИВОВОСПАЛИТЕЛЬНЫЙ ПРЕПАРАТ МЕЛОКСИКАМ ОСЛАБЛЯЕТ ЭФФЕКТ ИММУНОМОДУЛЯТОРА ГЛУТОКСИМА НА ТРАНСПОРТ Na+ В ЭПИТЕЛИИ КОЖИ ЛЯГУШКИ Мельницкая А. В. Melnitskaya A. V. avmelnitskaya@yandex.ru Крутецкая З. И. Krutetskaya Z. I. z.krutetskya@spbu.ru Антонов В. Г. Antonov V. G. Крутецкая Н. И. Krutetskaya N. I. Бадюлина В. И. Badulina V. I. Санкт-Петербургский государственный университет Санкт-Петербург Россия Saint-Petersburg State University Saint Petersburg Russian Federation Санкт-Петербургский государственный университет Санкт-Петербург Россия Saint-Petersburg State University Saint Petersburg Russian Federation Санкт-Петербургский государственный педиатрический медицинский университет Санкт-Петербург Россия Saint-Petersburg State Pediatric Medical University Saint Petersburg Russian Federation Военно-Медицинская академия им. C.М. Кирова Санкт-Петербург Россия Kirov Military Medical Academy Saint Petersburg Russian Federation Санкт-Петербургский государственный университет Санкт-Петербург Россия Saint-Petersburg State University Saint Petersburg Russian Federation Санкт-Петербургский государственный университет Санкт-Петербург Россия Saint-Petersburg State University Saint Petersburg Russian Federation 27 05 2024 27 05 2024 8 3 328 332 20 07 2023 https://rusjbpc.ru/en/nauka/article/83371/view

Статья посвящена исследованию редокс-регуляции трансэпителиального транспорта ионов в осморегулирующих эпителиях. Фармакологический аналог окисленного глутатиона препарат глутоксим® обладает антиоксидантными и радиопротекторными свойствами и широко применяется в качестве иммуномодулятора и цитопротектора в комплексной терапии бактериальных, вирусных и онкологических заболеваний. С использованием метода фиксации потенциала исследовано влияние ингибитора циклооксигеназного пути окисления арахидоновой кислоты - нестероидного противовоспалительного препарата мелоксикама на эффект глутоксима на транспорт Na+ в эпителии кожи лягушки Rana temporaria. Впервые показано, что преинкубация кожи лягушки с мелоксикамом существенно снижает стимулирующее действие глутоксима на транспорт Na+. Полученные данные свидетельствуют об участии циклооксигеназного пути окисления арахидоновой кислоты в действии глутоксима на транспорт Na+ в эпителии кожи лягушки. Полученные результаты способствуют также более детальному пониманию молекулярных механизмов фармакологического действия глутоксима и мелоксикама, и могут быть полезны для применения этих препаратов в клинической практике.

The article is devoted to the study of redox regulation of transepithelial ion transport in osmoregulatory epithelium. The pharmacological analogue of oxidized glutathione, drug glutoxim®, has antioxidant and radioprotective properties and is widely used as an immunomodulator and cytoprotector in complex therapy of bacterial, viral and oncological diseases. Using voltage-clamp technique, the influence of non-steroidal anti-inflammatory drug meloxicam, an inhibitor of the cyclooxygenase pathway of arachidonic acid oxidation, on glutoxim effect on Na+ transport in frog Rana temporaria skin was investigated. It was shown for the first time that frog skin preincubation with meloxicam significantly reduces the stimulatory effect of glutoxim on Na+ transport. The data obtained indicate the involvement of cyclooxygenase pathway of arachidonic acid oxidation in the effect of glutoxim on Na+ transport in frog skin epithelium. The results also contribute to a more detailed understanding of molecular mechanisms of pharmacological effect of glutoxim and meloxicam, and may be useful for their application in clinics.

 транспорт Na+ глутоксим мелоксикам эпителий кожи лягушки Na+ transport glutoxim meloxicam frog skin epithelium Работа выполнена в рамках плановых тем Кафедры биофизики Санкт-Петербургского государственного университета и Кафедры биохимии Санкт-Петербургского государственного педиатрического медицинского университета, а также Договора на выполнение научно-исследовательских работ № 05/03-20.

Наточин Ю.В. Основы физиологии почки. Л.: Наука, 1982, 184 с. Natochin Yu.V. Fundamentals of kidney physiology. L.: Nauka, 1982, 184 p. (In Russ.). Zhukov O.B., Zubarev A.R., Mezentseva M.V., Andryushkova Yu.A., Ose I.V. Modern aspects of immunomodulating therapy for those sick with recurrent infections of sexual transmission and with antibiotic-resistant bacterial prostatitis. Vracheb. Sosl., 2004, vol. 5/6, pp. 51-56. Zhukov O.B., Zubarev A.R., Mezentseva M.V., Andryushkova Yu.A., Ose I.V. Modern aspects of immunomodulating therapy for those sick with recurrent infections of sexual transmission and with antibiotic-resistant bacterial prostatitis. Vracheb. Sosl., 2004, vol. 5/6, pp. 51-56. Krutetskaya Z.I., Lebedev O.E., Melnitskaya A.V., Antonov V.G., Nozdrachev A.D. Effect of disulfide-containing agents on the Na+ transport in the frog skin. Doklady Biological Sciences, 2008, vol. 421, pp. 235-238. Krutetskaya Z.I., Lebedev O.E., Melnitskaya A.V., Antonov V.G., Nozdrachev A.D. Effect of disulfide-containing agents on the Na+ transport in the frog skin. Doklady Biological Sciences, 2008, vol. 421, pp. 235-238. Melnitskaya A.V., Krutetskaya Z.I., Lebedev O.E., Antonov V.G., Butov S.N. Involvement of tyrosine and phosphatidylinositol kinases in oxidized glutathione and glutoxim regulation of Na+ transport in frog skin. Cell and Tissue Biology, 2010, vol. 4, no. 3, pp. 273-279. Melnitskaya A.V., Krutetskaya Z.I., Lebedev O.E., Antonov V.G., Butov S.N. Involvement of tyrosine and phosphatidylinositol kinases in oxidized glutathione and glutoxim regulation of Na+ transport in frog skin. Cell and Tissue Biology, 2010, vol. 4, no. 3, pp. 273-279. Melnitskaya A.V., Krutetskaya Z.I., Lebedev O.E. The involvement of protein kinase C in the effect of oxidized glutathione and glutoxim on Na+ transport in frog skin. Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology, 2009, vol. 3, no. 3, pp. 323. Melnitskaya A.V., Krutetskaya Z.I., Lebedev O.E. The involvement of protein kinase C in the effect of oxidized glutathione and glutoxim on Na+ transport in frog skin. Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology, 2009, vol. 3, no. 3, pp. 323. Melnitskaya A.V., Krutetskaya Z.I., Lebedev O.E., Butov S.N., Krutetskaya N.I., Antonov V.G. The effect of glutoxim on Na+ transport in frog skin: the role of cytoskeleton. Cell and Tissue Biology, 2012, vol. 6, no. 3, pp. 248-253. Melnitskaya A.V., Krutetskaya Z.I., Lebedev O.E., Butov S.N., Krutetskaya N.I., Antonov V.G. The effect of glutoxim on Na+ transport in frog skin: the role of cytoskeleton. Cell and Tissue Biology, 2012, vol. 6, no. 3, pp. 248-253. Krutetskaya Z.I., Melnitskaya A.V., Antonov V.G., Nozdrachev A.D. The involvement of microtubules in the glutoxim regulation of Na+ transport in the frog skin. Doklady Biological Sciences, 2012, vol. 445, pp. 227-229. Krutetskaya Z.I., Melnitskaya A.V., Antonov V.G., Nozdrachev A.D. The involvement of microtubules in the glutoxim regulation of Na+ transport in the frog skin. Doklady Biological Sciences, 2012, vol. 445, pp. 227-229. Wang B., Wu L., Chen J., Dong L., Chen C., Wen Z., Hu J., Fleming I., Wang D.W. Metabolism pathways of arachidonic acids: mechanisms and potential therapeutic targets. Signal Transduc. Target. Ther., 2021, vol. 26, no. 6(1), p. 94, doi: 10.1038/s41392-020-00443-w. Wang B., Wu L., Chen J., Dong L., Chen C., Wen Z., Hu J., Fleming I., Wang D.W. Metabolism pathways of arachidonic acids: mechanisms and potential therapeutic targets. Signal Transduc. Target. Ther., 2021, vol. 26, no. 6(1), p. 94, doi: 10.1038/s41392-020-00443-w. Els W.J., Helman S.H. Dual role of prostaglandins (PGE2) in regulation of channel density and open probability of epithelial Na+ channels in frog skin (R. pipiens). J. Membr. Biol., 1997, vol. 155, no. 1, pp. 75-87, doi: 10.1007/s002329900159. Els W.J., Helman S.H. Dual role of prostaglandins (PGE2) in regulation of channel density and open probability of epithelial Na+ channels in frog skin (R. pipiens). J. Membr. Biol., 1997, vol. 155, no. 1, pp. 75-87, doi: 10.1007/s002329900159. Shakhmatova E.I., Kuznetsova A.A., Prutskova N.P., Bogolepova A.E., Natochin Iu.V. The effect of cyclooxygenase inhibitors on ion and water transport in the human kidney and frog skin and bladder. Ross. Fiziol. Zh. Im. I M. Sechenova, 1997, vol. 83, no. 10, pp. 68-75. Shakhmatova E.I., Kuznetsova A.A., Prutskova N.P., Bogolepova A.E., Natochin Iu.V. The effect of cyclooxygenase inhibitors on ion and water transport in the human kidney and frog skin and bladder. Ross. Fiziol. Zh. Im. I M. Sechenova, 1997, vol. 83, no. 10, pp. 68-75. Ordway R.W., Singer J.J., Walsh J.V. Jr. Direct regulation of ion channels by fatty acids. Trends Neurosci., 1991, vol. 14, pp. 96-100. Ordway R.W., Singer J.J., Walsh J.V. Jr. Direct regulation of ion channels by fatty acids. Trends Neurosci., 1991, vol. 14, pp. 96-100. Meves H. Arachidonic acid and ion channels: an update. Br. J. Pharmacol., 2008, vol. 155, pp. 14-16. Meves H. Arachidonic acid and ion channels: an update. Br. J. Pharmacol., 2008, vol. 155, pp. 14-16. Pavlov T.S., Ilatovskaya D., Levchenko V., Mattson D.L, Roman R.J., Staruschenko A. Effects of cytochrome P-450 metabolites of arachidonic acid on the epithelial sodium channel (ENaC). Am. J. Physiol., 2011, vol, 301, pp. F672-F681. Pavlov T.S., Ilatovskaya D., Levchenko V., Mattson D.L, Roman R.J., Staruschenko A. Effects of cytochrome P-450 metabolites of arachidonic acid on the epithelial sodium channel (ENaC). Am. J. Physiol., 2011, vol, 301, pp. F672-F681. Engelhardt G., Bögel R., Schnitzler Chr., Utzmann R. Meloxicam: Influence on arachidonic acid metabolism. Part I. In vitro findings. Biochem. Pharmacol., 1996, vol. 51, pp. 29-38. Engelhardt G., Bögel R., Schnitzler Chr., Utzmann R. Meloxicam: Influence on arachidonic acid metabolism. Part I. In vitro findings. Biochem. Pharmacol., 1996, vol. 51, pp. 29-38. Vasilenko K.P., Burova E.B., Antonov V.G., Nikolskii N.N. Oxidized glutathione induces activation of the epidermal growth factor receptor and MAP kinases ERK 1, 2, Tsitologiya, 2006, vol. 48, no. 6, pp. 500-507. Vasilenko K.P., Burova E.B., Antonov V.G., Nikolskii N.N. Oxidized glutathione induces activation of the epidermal growth factor receptor and MAP kinases ERK 1, 2, Tsitologiya, 2006, vol. 48, no. 6, pp. 500-507. Burova E.B., Vasilenko K.P., Antonov V.D., Nikolskii N.N. Transactivation of the epidermal growth factor receptor by oxidized glutathione and its pharmacological analogue glutoxim in A431 cells. Dokl. Biol. Sci., 2005, vol. 404, pp. 392-394. Burova E.B., Vasilenko K.P., Antonov V.D., Nikolskii N.N. Transactivation of the epidermal growth factor receptor by oxidized glutathione and its pharmacological analogue glutoxim in A431 cells. Dokl. Biol. Sci., 2005, vol. 404, pp. 392-394. Sejoong Kim M.D., Kwon Wook Joo M.D. Electrolyte and acid-base disturbances associated with non-steroidal anti-inflammatory drugs. Electrolytes Blood Pressure, 2007, vol. 5, no. 2, pp. 116-125. Sejoong Kim M.D., Kwon Wook Joo M.D. Electrolyte and acid-base disturbances associated with non-steroidal anti-inflammatory drugs. Electrolytes Blood Pressure, 2007, vol. 5, no. 2, pp. 116-125. Black H.E. Renal toxicity of non-steroidal anti-inflammatory drugs. Toxicologic pathologic, 1986, vol. 14, no. 1, pp. 83-90. Black H.E. Renal toxicity of non-steroidal anti-inflammatory drugs. Toxicologic pathologic, 1986, vol. 14, no. 1, pp. 83-90. Park J.H., Park Y.S., Lee J.B., Park K.H., Paik M.K., Jeong M., Koh H.C. Meloxicam inhibits fipronil-induced apoptosis via modulation of the oxidative stress and inflammatory response in SH-SY5Y cells. J. Appl. Toxicol., 2016, vol. 36, pp. 10–23. Park J.H., Park Y.S., Lee J.B., Park K.H., Paik M.K., Jeong M., Koh H.C. Meloxicam inhibits fipronil-induced apoptosis via modulation of the oxidative stress and inflammatory response in SH-SY5Y cells. J. Appl. Toxicol., 2016, vol. 36, pp. 10–23. Pawlukianiec C., Gryciuk M.E., Mil K.M., Zendzian-Piotrowska M., Zalewska A., Maciejczyk M.A New insight into meloxicam: Assessment of antioxidant and anti-glycating activity in in vitro studies. Pharmaceuticals (Basel), 2020, vol. 13, no. 9, p. 240. Pawlukianiec C., Gryciuk M.E., Mil K.M., Zendzian-Piotrowska M., Zalewska A., Maciejczyk M.A New insight into meloxicam: Assessment of antioxidant and anti-glycating activity in in vitro studies. Pharmaceuticals (Basel), 2020, vol. 13, no. 9, p. 240. Tasaki Y., Yamamoto J., Omura T., Noda T., Kamiyama N., Yoshida K., Satomi M., Sakaguchi T., Asari M., Ohkubo T., Shimizu K., Matsubara K. Oxicam structure in non-steroidal anti-inflammatory drugs is essential to exhibit Akt-mediated neuroprotection against 1-methyl-4-phenyl pyridinium-induced cytotoxicity. Eur. J. Pharmacol., 2012, vol. 676, pp. 57-63. Tasaki Y., Yamamoto J., Omura T., Noda T., Kamiyama N., Yoshida K., Satomi M., Sakaguchi T., Asari M., Ohkubo T., Shimizu K., Matsubara K. Oxicam structure in non-steroidal anti-inflammatory drugs is essential to exhibit Akt-mediated neuroprotection against 1-methyl-4-phenyl pyridinium-induced cytotoxicity. Eur. J. Pharmacol., 2012, vol. 676, pp. 57-63.