اثرحفاظتی مکمل کوآنزیم Q10بر استرس اکسیداتیو و آسیب بافتی ناشی از نیکوتین در تخمدان موشهای صحرایی
الموضوعات :
شهناز یوسفی زاده
1
,
علی لوئی منفرد
2
,
یحیی محمدی
3
1 - استادیار گروه علوم آزمایشگاهی و درمانگاهی، دانشکده پیرادامپزشکی، دانشگاه ایلام، ایلام، ایران.
2 - دانشیار گروه بافتشناسی و میکروبشناسی، دانشکده پیرادامپزشکی، دانشگاه ایلام، ایلام، ایران.
3 - دانشیار گروه علوم دامی، دانشکده کشاورزی، دانشگاه ایلام،ایلام، ایران.
تاريخ الإرسال : 10 الأربعاء , رجب, 1444
تاريخ التأكيد : 08 الأحد , ذو القعدة, 1444
تاريخ الإصدار : 28 السبت , جمادى الثانية, 1444
الکلمات المفتاحية:
تخمدان,
موش صحرایی,
استرس اکسیداتیو,
نیکوتین,
مکمل کوآنزیم Q10,
ملخص المقالة :
نیکوتین بهعنوان یک سم، اثرات غیرقابل جبرانی بر بافتهای مختلف بدن از جمله دستگاه تناسلی به جای میگذارد. کوآنزیمQ10 تاثیر شگرفی در بالابردن سطح آنتیاکسیدانی بدن و ممانعت از مسمومیت ها دارد.در مطالعه حاضر اثر محافظتی مکمل کوآنزیمQ10 بر تغییرات ناشی از نیکوتین در تخمدان موش صحرایی بررسی شد. بدین منظور، تعداد 32سر موش صحرایی ماده بالغ نژاد ویستار، بهصورت تصادفی به 4 گروه 8تایی تقسیم شدند. موش های گروه اول (شاهد) فقط با جیره غذایی معمول تغذیه شدند، اما حیوانات گروه دوم با استفاده از نیکوتین به میزان mg/kg 2/0 ، موش های گروه سوم با استفاده از کوآنزیم Q10 به میزانmg/kg 75 و حیوانات گروه چهارم، همزمان با استفاده از نیکوتین و کوانزیم Q10 (با همان مقادیر) از طریق گاواژ، تیمار شدند. در پایان دوره مطالعه (45 روز)، حیوانات آسانکشی شده و نمونه خون برای بررسی های هورمونی و عوامل آنتیاکسیدانی اخذ شد. همچنین از بافت تخمدان برای مطالعات بافت شناسی نمونه گیری انجام شد. در حیوانات تیمارشده با نیکوتین افزایش آترزی فولیکولی، آسیبهای بافتی، افزایش مالون دی آلدئید و نیتریک اکساید همراه با کاهش تعداد فولیکول های تخمدانی، کاهش میزان هورمون های استروژن و محرک فولیکول و فعالیت آنزیم های آنتی اکسیدانی سوپرکسید دیسموتاز، گلوتاتیون پرکسیداز و کاتالاز مشاهده شد. اما در حیوانات دریافتکننده همزمان نیکوتین و کوانزیم Q10، بهبودی قابل توجهی در عملکرد و ساختار تخمدان رخ داد. این مطالعه نشان می دهد که کوآنزیم Q10 با مکانیسم ایجاد توازن در وضعیت آنتیاکسیدانی و میزان هورمون های تولیدمثلی میتواند در برابر استرس اکسیداتیو و تغییرات بافتی ناشی از نیکوتین در تخمدان موش ها نقش محافظتی داشته باشد.
المصادر:
Bentov, Y., Esfandiari, N., Burstein, E. and Casper, R.F. (2010). The use of mitochondrial nutrients to improve the outcome of infertility treatment in older patients. Fertility and Sterility, 93(1): 272-275.
Bentov, Y., Yavorska, T., Esfandiari, N., Jurisicova, A. and Casper, R.F. (2011). The contribution of mitochondrial function to reproductive aging. Journal of Assisted Reproduction and Genetics, 28(9): 773-783.
Bruin, J.E., Gerstein, H.C. and Holloway, A.C. (2010). Long-term consequences of fetal and neonatal nicotine exposure: a critical review. Toxicolical Sciences, 116(2): 364-374.
Cheng, S.F., Qin, X.S., Han, Z.L., Sun, X.F., Feng, Y.N., Yang, F., et al. (2018). Nicotine exposure impairs germ cell development in human fetal ovaries cultured in vitro. Aging, (Albany NY),10(7): 1556-1574.
Darabi, Z., Basir, Z., Tabandeh, M. R. and Ghotbeddin, Z. (2022). Coenzyme Q10 improves ovarian histology and attenuates the expression of angiogenesis-associated proteins in the ovary of rats with experimental hyperstimulation syndrome. Iranian Journal of Basic Medical Sciences, 25(8): 989-996.
Dechanet, C., Anahory, T., Mathieu Daude, J.C., Quantin, X., Reyftmann, L., Hamamah, S., et al. (2011). Effects of cigarette smoking on reproduction. Human Reproduction Update, 17(1): 76-95.
Emmen, J.M., Couse, J.F., Elmore, S.A., Yates, M.M., Kissling, G.E. and Korach, K.S. (2005). In vitro growth and ovulation of follicles from ovaries of estrogen receptor (ER){alpha} and ER{beta} null mice indicate a role for ER{beta} in follicular maturation. Endocrinology, 146(6): 2817-2826.
Faghani, M., Saedi, S., Khanaki, K. and Mohammadghasemi, F. (2022). Ginseng alleviates folliculogenesis disorders via induction of cell proliferation and downregulation of apoptotic markers in nicotine-treated mice. Journal of Ovarian Research, 15(1): 14.
Florou, P., Anagnostis, P., Theocharis, P., Chourdakis, M. and Goulis, D.G. (2020). Does coenzyme Q10 supplementation improve fertility outcomes in women undergoing assisted reproductive technology procedures? A systematic review and meta-analysis of randomized-controlled trials. Journal of Assisted Reproduction and Genetics, 37(10): 2377-2387.
Gutierrez-Mariscal, F.M., Arenas-de Larriva, A.P., Limia-Perez, L., Romero-Cabrera, J.L., Yubero-Serrano, E.M. and López-Miranda, J. (2020). Coenzyme Q10 supplementation for the reduction of oxidative stress: Clinical implications in the treatment of chronic diseases. International Journal of Molecular Sciences, 21(21): 7870.
Halliwell, B. (2012). Free radicals and antioxidants: updating a personal view. Nutrition Reviews, 70(5): 257-265.
Heaton, R.A., Heales, S., Rahman, K., Sexton, D.W. and Hargreaves, I. (2020). The effect of cellular coenzyme Q(10) deficiency on lysosomal acidification. Journal of Clinical Medicine, 9(6): 1923.
Holloway, A.C., Kellenberger, L.D. and Petrik, J.J. (2006). Fetal and neonatal exposure to nicotine disrupts ovarian function and fertility in adult female rats. Endocrinology, 30(2): 213-216.
Hornos Carneiro, M.F., Shin, N., Karthikraj, R., Barbosa, F.Jr., Kannan, K. and Colaiácovo, M.P. (2020). Antioxidant CoQ10 Restores Fertility by Rescuing Bisphenol A-Induced Oxidative DNA Damage in the Caenorhabditis elegans Germline. Genetics, 214(2): 381-395.
Jennings, P.C., Merriman, J.A., Beckett, E.L., Hansbro, P.M. and Jones, K.T. (2011). Increased zona pellucida thickness and meiotic spindle disruption in oocytes from cigarette smoking mice. Human Reproduction, 26(4): 878-884.
Karami, E., Goodarzi, Z., Ghanbari, A., Dehdashti, A., Bandegi, A.R. and Yosefi, S. (2022). Dataset on biochemical markers and histological alterations in rat kidney intoxicated with cadmium chloride and treated with antioxidant. Data in Brief, 43: 1-11.
Kharrazi, M., DeLorenze, G.N., Kaufman, F.L., Eskenazi, B., Bernert, J.T.Jr, Graham, S., et al. (2004). Environmental tobacco smoke and pregnancy outcome. Epidemiology, 15(6): 660-670.
Kiremitli, T., Kiremitli, S., Akselim, B., Yilmaz, B., Mammadov, R., Tor, I.H., et al. (2021). Protective effect of Coenzyme Q10 on oxidative ovarian and uterine damage induced by methotrexate in rats. Human & Experimental Toxicology, 40(9): 1537-1544.
Kole, E., Ozkan, S.O., Eraldemir, C., Akar, F.Y., Ozbek, S.K., Kole, M.C., et al. (2020). Effects of melatonin on ovarian reserve in cigarette smoking: an experimental study. Archives of Medical Science, 16(6): 1376-1386.
MacMahon, B., Trichopoulos, D., Cole, P. and Brown, J. (1982). Cigarette smoking and urinary estrogens. The New England Journal of Medicine, 307(17): 1062-1065.
Marcondes, F., Bianchi, F. and Tanno, A. (2002). Determination of the estrous cycle phases of rats: some helpful considerations. Brazilian Journal of Biology, 62(4A): 609-614.
Mohammadghasemi, F., Jahromi, S.K., Hajizadeh, H., Homafar, M.A. and Saadat, N. (2012). The Protective Effects of Exogenous Melatonin on Nicotine-induced Changes in Mouse Ovarian Follicles. Journal of Reproduction and Fertility, 13(3): 143-150.
Mohammadghasemi, F. and Jahromi, S.K. (2018). Melatonin ameliorates testicular damages induced by nicotine in mice. Iranian Journal of Basic Medical Sciences, 21(6): 639-644.
Mohammadghasemi, F., Khanaki, K., Moravati, H. and Faghani, M. (2021). The amelioration of nicotine-induced reproductive impairment in male mouse by Sambucus ebulus fruit extract. Anatomy and Cell Biology, 54(2): 232-240.
Moshtaghi-Kashanian, G.R., Esmaeeli, F. and Dabiri, S. (2005). Enhanced prolactin levels in opium smokers. Addiction Biology, 10(4): 345-349.
Overvad, K., Diamant, B., Holm, L., Holmer, G., Mortensen, S.A. and Stender, S. (1999). Coenzyme Q10 in health and disease. European Journal of Clinical Nutrition, 53(10): 764-770.
Ozcan, P., Fıçıcıoğlu, C., Kizilkale, O., Yesiladali, M., Tok, O.E., Ozkan, F., et al. (2016). Can Coenzyme Q10 supplementation protect the ovarian reserve against oxidative damage? Journal of Assisted Reproduction and Genetics, 33(9): 1223-1230.
Ozcan, P., Ficicioglu, C. and Yesiladali, M. (2015). The protective effect of Coenzyme Q10 supplementation on decreased ovarian reserve in female Sprague-Dawley rats. Fertility and Sterility Abstract Only, 104(3): E255:437.
Ozlem, K., Emin, K. and Birkan Y. (2022). Protective effect of edaravone on cisplatin‑induced injury in rat ovary. Archives of Gynecology and Obstetrics, 306(5): 1673-1678.
Quinzii, C.M., Hirano, M. and DiMauro, S. (2007). CoQ10 Deficiency Diseases in Adults. Mitochondrion. 7(Supp): S122-126.
Rahmani Kahnemoei, J. (2016). The effect of passive inhalation of cigarette smoke on serum fat profile in rats. Journal of Veterinary Clinical Pathology, 10(3): 245-250. [In Persian]
Reuter, S., Gupta, S.C., Chaturvedi, M.M. and Aggarwal, B.B. (2010). Oxidative stress, inflammation, and cancer: how are they linked? Free Radical Biology and Medicine, 49(11): 1603-1616.
Selvaraju, S., Raghavendra, B.S., Subramani, T.S., Priyadharsini, R., Reddy, I.J., and Ravindra, J.P. (2010). Changes in luteal cells distribution, apoptotic rate, lipid peroxidation levels and antioxidant enzyme activities in buffalo (Bubalus bubalis) corpus luteum. Animal Reproduction Science, 120(1-4): 39-46.
Shahin, A.M., Bahrami, A.M., Delkhosh, A. and Shakarami, N. (2022). Evaluation of the effect of Aloevera gel on ovarian tissue structure in Nicotine-receiving Rats. Veterinary Clinical Pathology, 15(4): 319-331. [In Persian]
Sinha-Hikim, I., Friedman, T.C., Falz, M., Chalfant, V., Hasan, M.K., Espinoza-Derout, J., et al. (2017). Nicotine plus a high-fat diet triggers cardiomyocyte apoptosis. Cell and Tissue Research, 368(1): 159-170.
Valavanidis, A., Vlachogianni, T. and Fiotakis, K. (2009). Tobacco smoke: involvement of reactive oxygen species and stable free radicals in mechanisms of oxidative damage, carcinogenesis and synergistic effects with other respirable particles. International Journal of Environmental Research and Public Health, 6(2): 445-462.
Wang, Y.F., Sun, X.F., Han, Z.L., Li, L., Ge, W., Zhao, Y., et al. (2018). Protective effects of melatonin against nicotine-induced disorder of mouse early folliculogenesis. Aging (Albany NY), 10(3): 463-480.
Weydert, C.J. and Cullen, J.J. (2010). Measurement of superoxide dismutase, catalase and glutathione peroxidase in cultured cells and tissue. Nature Protocols, 5(1): 51-66.
Xu, Y., Nisenblat, V., Lu, C., Li, R., Qiao, J., Zhen, X. and Wang, S. (2018). Pretreatment with coenzyme Q10 improves ovarian response and embryo quality in low-prognosis young women with decreased ovarian reserve: a randomized controlled trial. Reproductive Biology and Endocrinology, 16(1): 29.
Zhang, T., He, Q., Xiu, H., Zhang, Z., Liu, Y., Chen, Z. and Hu, H. (2022). Efficacy and Safety of Coenzyme Q10 Supplementation in the Treatment of Polycystic Ovary Syndrome: a Systematic Review and Meta-analysis. Reproductive Sciences, 30(4): 1033-1048.
Zhao, S., Wu, W., Liao, J., Zhang, X., Shen, M., Li, X., Lin, Q. and Cao, C. (2022). Molecular mechanisms underlying the renal protective effects of coenzyme Q10 in acute kidney injury. Cellular & Molecular Biology Letters, 27(1): 57.
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Bentov, Y., Esfandiari, N., Burstein, E. and Casper, R.F. (2010). The use of mitochondrial nutrients to improve the outcome of infertility treatment in older patients. Fertility and Sterility, 93(1): 272-275.
Bentov, Y., Yavorska, T., Esfandiari, N., Jurisicova, A. and Casper, R.F. (2011). The contribution of mitochondrial function to reproductive aging. Journal of Assisted Reproduction and Genetics, 28(9): 773-783.
Bruin, J.E., Gerstein, H.C. and Holloway, A.C. (2010). Long-term consequences of fetal and neonatal nicotine exposure: a critical review. Toxicolical Sciences, 116(2): 364-374.
Cheng, S.F., Qin, X.S., Han, Z.L., Sun, X.F., Feng, Y.N., Yang, F., et al. (2018). Nicotine exposure impairs germ cell development in human fetal ovaries cultured in vitro. Aging, (Albany NY),10(7): 1556-1574.
Darabi, Z., Basir, Z., Tabandeh, M. R. and Ghotbeddin, Z. (2022). Coenzyme Q10 improves ovarian histology and attenuates the expression of angiogenesis-associated proteins in the ovary of rats with experimental hyperstimulation syndrome. Iranian Journal of Basic Medical Sciences, 25(8): 989-996.
Dechanet, C., Anahory, T., Mathieu Daude, J.C., Quantin, X., Reyftmann, L., Hamamah, S., et al. (2011). Effects of cigarette smoking on reproduction. Human Reproduction Update, 17(1): 76-95.
Emmen, J.M., Couse, J.F., Elmore, S.A., Yates, M.M., Kissling, G.E. and Korach, K.S. (2005). In vitro growth and ovulation of follicles from ovaries of estrogen receptor (ER){alpha} and ER{beta} null mice indicate a role for ER{beta} in follicular maturation. Endocrinology, 146(6): 2817-2826.
Faghani, M., Saedi, S., Khanaki, K. and Mohammadghasemi, F. (2022). Ginseng alleviates folliculogenesis disorders via induction of cell proliferation and downregulation of apoptotic markers in nicotine-treated mice. Journal of Ovarian Research, 15(1): 14.
Florou, P., Anagnostis, P., Theocharis, P., Chourdakis, M. and Goulis, D.G. (2020). Does coenzyme Q10 supplementation improve fertility outcomes in women undergoing assisted reproductive technology procedures? A systematic review and meta-analysis of randomized-controlled trials. Journal of Assisted Reproduction and Genetics, 37(10): 2377-2387.
Gutierrez-Mariscal, F.M., Arenas-de Larriva, A.P., Limia-Perez, L., Romero-Cabrera, J.L., Yubero-Serrano, E.M. and López-Miranda, J. (2020). Coenzyme Q10 supplementation for the reduction of oxidative stress: Clinical implications in the treatment of chronic diseases. International Journal of Molecular Sciences, 21(21): 7870.
Halliwell, B. (2012). Free radicals and antioxidants: updating a personal view. Nutrition Reviews, 70(5): 257-265.
Heaton, R.A., Heales, S., Rahman, K., Sexton, D.W. and Hargreaves, I. (2020). The effect of cellular coenzyme Q(10) deficiency on lysosomal acidification. Journal of Clinical Medicine, 9(6): 1923.
Holloway, A.C., Kellenberger, L.D. and Petrik, J.J. (2006). Fetal and neonatal exposure to nicotine disrupts ovarian function and fertility in adult female rats. Endocrinology, 30(2): 213-216.
Hornos Carneiro, M.F., Shin, N., Karthikraj, R., Barbosa, F.Jr., Kannan, K. and Colaiácovo, M.P. (2020). Antioxidant CoQ10 Restores Fertility by Rescuing Bisphenol A-Induced Oxidative DNA Damage in the Caenorhabditis elegans Germline. Genetics, 214(2): 381-395.
Jennings, P.C., Merriman, J.A., Beckett, E.L., Hansbro, P.M. and Jones, K.T. (2011). Increased zona pellucida thickness and meiotic spindle disruption in oocytes from cigarette smoking mice. Human Reproduction, 26(4): 878-884.
Karami, E., Goodarzi, Z., Ghanbari, A., Dehdashti, A., Bandegi, A.R. and Yosefi, S. (2022). Dataset on biochemical markers and histological alterations in rat kidney intoxicated with cadmium chloride and treated with antioxidant. Data in Brief, 43: 1-11.
Kharrazi, M., DeLorenze, G.N., Kaufman, F.L., Eskenazi, B., Bernert, J.T.Jr, Graham, S., et al. (2004). Environmental tobacco smoke and pregnancy outcome. Epidemiology, 15(6): 660-670.
Kiremitli, T., Kiremitli, S., Akselim, B., Yilmaz, B., Mammadov, R., Tor, I.H., et al. (2021). Protective effect of Coenzyme Q10 on oxidative ovarian and uterine damage induced by methotrexate in rats. Human & Experimental Toxicology, 40(9): 1537-1544.
Kole, E., Ozkan, S.O., Eraldemir, C., Akar, F.Y., Ozbek, S.K., Kole, M.C., et al. (2020). Effects of melatonin on ovarian reserve in cigarette smoking: an experimental study. Archives of Medical Science, 16(6): 1376-1386.
MacMahon, B., Trichopoulos, D., Cole, P. and Brown, J. (1982). Cigarette smoking and urinary estrogens. The New England Journal of Medicine, 307(17): 1062-1065.
Marcondes, F., Bianchi, F. and Tanno, A. (2002). Determination of the estrous cycle phases of rats: some helpful considerations. Brazilian Journal of Biology, 62(4A): 609-614.
Mohammadghasemi, F., Jahromi, S.K., Hajizadeh, H., Homafar, M.A. and Saadat, N. (2012). The Protective Effects of Exogenous Melatonin on Nicotine-induced Changes in Mouse Ovarian Follicles. Journal of Reproduction and Fertility, 13(3): 143-150.
Mohammadghasemi, F. and Jahromi, S.K. (2018). Melatonin ameliorates testicular damages induced by nicotine in mice. Iranian Journal of Basic Medical Sciences, 21(6): 639-644.
Mohammadghasemi, F., Khanaki, K., Moravati, H. and Faghani, M. (2021). The amelioration of nicotine-induced reproductive impairment in male mouse by Sambucus ebulus fruit extract. Anatomy and Cell Biology, 54(2): 232-240.
Moshtaghi-Kashanian, G.R., Esmaeeli, F. and Dabiri, S. (2005). Enhanced prolactin levels in opium smokers. Addiction Biology, 10(4): 345-349.
Overvad, K., Diamant, B., Holm, L., Holmer, G., Mortensen, S.A. and Stender, S. (1999). Coenzyme Q10 in health and disease. European Journal of Clinical Nutrition, 53(10): 764-770.
Ozcan, P., Fıçıcıoğlu, C., Kizilkale, O., Yesiladali, M., Tok, O.E., Ozkan, F., et al. (2016). Can Coenzyme Q10 supplementation protect the ovarian reserve against oxidative damage? Journal of Assisted Reproduction and Genetics, 33(9): 1223-1230.
Ozcan, P., Ficicioglu, C. and Yesiladali, M. (2015). The protective effect of Coenzyme Q10 supplementation on decreased ovarian reserve in female Sprague-Dawley rats. Fertility and Sterility Abstract Only, 104(3): E255:437.
Ozlem, K., Emin, K. and Birkan Y. (2022). Protective effect of edaravone on cisplatin‑induced injury in rat ovary. Archives of Gynecology and Obstetrics, 306(5): 1673-1678.
Quinzii, C.M., Hirano, M. and DiMauro, S. (2007). CoQ10 Deficiency Diseases in Adults. Mitochondrion. 7(Supp): S122-126.
Rahmani Kahnemoei, J. (2016). The effect of passive inhalation of cigarette smoke on serum fat profile in rats. Journal of Veterinary Clinical Pathology, 10(3): 245-250. [In Persian]
Reuter, S., Gupta, S.C., Chaturvedi, M.M. and Aggarwal, B.B. (2010). Oxidative stress, inflammation, and cancer: how are they linked? Free Radical Biology and Medicine, 49(11): 1603-1616.
Selvaraju, S., Raghavendra, B.S., Subramani, T.S., Priyadharsini, R., Reddy, I.J., and Ravindra, J.P. (2010). Changes in luteal cells distribution, apoptotic rate, lipid peroxidation levels and antioxidant enzyme activities in buffalo (Bubalus bubalis) corpus luteum. Animal Reproduction Science, 120(1-4): 39-46.
Shahin, A.M., Bahrami, A.M., Delkhosh, A. and Shakarami, N. (2022). Evaluation of the effect of Aloevera gel on ovarian tissue structure in Nicotine-receiving Rats. Veterinary Clinical Pathology, 15(4): 319-331. [In Persian]
Sinha-Hikim, I., Friedman, T.C., Falz, M., Chalfant, V., Hasan, M.K., Espinoza-Derout, J., et al. (2017). Nicotine plus a high-fat diet triggers cardiomyocyte apoptosis. Cell and Tissue Research, 368(1): 159-170.
Valavanidis, A., Vlachogianni, T. and Fiotakis, K. (2009). Tobacco smoke: involvement of reactive oxygen species and stable free radicals in mechanisms of oxidative damage, carcinogenesis and synergistic effects with other respirable particles. International Journal of Environmental Research and Public Health, 6(2): 445-462.
Wang, Y.F., Sun, X.F., Han, Z.L., Li, L., Ge, W., Zhao, Y., et al. (2018). Protective effects of melatonin against nicotine-induced disorder of mouse early folliculogenesis. Aging (Albany NY), 10(3): 463-480.
Weydert, C.J. and Cullen, J.J. (2010). Measurement of superoxide dismutase, catalase and glutathione peroxidase in cultured cells and tissue. Nature Protocols, 5(1): 51-66.
Xu, Y., Nisenblat, V., Lu, C., Li, R., Qiao, J., Zhen, X. and Wang, S. (2018). Pretreatment with coenzyme Q10 improves ovarian response and embryo quality in low-prognosis young women with decreased ovarian reserve: a randomized controlled trial. Reproductive Biology and Endocrinology, 16(1): 29.
Zhang, T., He, Q., Xiu, H., Zhang, Z., Liu, Y., Chen, Z. and Hu, H. (2022). Efficacy and Safety of Coenzyme Q10 Supplementation in the Treatment of Polycystic Ovary Syndrome: a Systematic Review and Meta-analysis. Reproductive Sciences, 30(4): 1033-1048.
Zhao, S., Wu, W., Liao, J., Zhang, X., Shen, M., Li, X., Lin, Q. and Cao, C. (2022). Molecular mechanisms underlying the renal protective effects of coenzyme Q10 in acute kidney injury. Cellular & Molecular Biology Letters, 27(1): 57.