<?xml version='1.0' encoding='utf-8'?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.2 20190208//EN" "http://jats.nlm.nih.gov/publishing/1.2/JATS-journalpublishing1.dtd">
<article article-type="research-article" dtd-version="1.2" xml:lang="ru" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><front><journal-meta><journal-id journal-id-type="issn">2658-6533</journal-id><journal-title-group><journal-title>Research Results in Biomedicine</journal-title></journal-title-group><issn pub-type="epub">2658-6533</issn></journal-meta><article-meta><article-id pub-id-type="doi">10.18413/2658-6533-2024-10-2-0-5</article-id><article-id pub-id-type="publisher-id">3422</article-id><article-categories><subj-group subj-group-type="heading"><subject>Pharmacology</subject></subj-group></article-categories><title-group><article-title>&lt;strong&gt;Potential protective effect of alpha lipoic acid against testicular oxidative stress and altered gene expression induced by gentamicin treatment&lt;/strong&gt;&lt;br /&gt;
&amp;nbsp;</article-title><trans-title-group xml:lang="en"><trans-title>&lt;strong&gt;Potential protective effect of alpha lipoic acid against testicular oxidative stress and altered gene expression induced by gentamicin treatment&lt;/strong&gt;&lt;br /&gt;
&amp;nbsp;</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><name-alternatives><name xml:lang="ru"><surname>Elsawah</surname><given-names>Hozaifa K.</given-names></name><name xml:lang="en"><surname>Elsawah</surname><given-names>Hozaifa K.</given-names></name></name-alternatives><email>hozaifa2005@gmail.com</email></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="ru"><surname>Mokhimar</surname><given-names>Haitham M.</given-names></name><name xml:lang="en"><surname>Mokhimar</surname><given-names>Haitham M.</given-names></name></name-alternatives><email>hitthammohamed@gmail.com</email></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="ru"><surname>Kandiel</surname><given-names>Mohamed M.</given-names></name><name xml:lang="en"><surname>Kandiel</surname><given-names>Mohamed M.</given-names></name></name-alternatives><email>mohamed.kandil@fvtm.bu.edu.eg</email></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="ru"><surname>Farid</surname><given-names>Ayman S.</given-names></name><name xml:lang="en"><surname>Farid</surname><given-names>Ayman S.</given-names></name></name-alternatives><email>ayman.samir@fvtm.bu.edu.eg</email></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="ru"><surname>El-Mahmoudy</surname><given-names>AbuBakr M.</given-names></name><name xml:lang="en"><surname>El-Mahmoudy</surname><given-names>AbuBakr M.</given-names></name></name-alternatives><email>a.elmahmoudy@fvtm.bu.edu.eg</email></contrib></contrib-group><pub-date pub-type="epub"><year>2024</year></pub-date><volume>10</volume><issue>2</issue><fpage>0</fpage><lpage>0</lpage><self-uri content-type="pdf" xlink:href="/media/medicine/2024/2/Биомедицинские_исследования-65-74.pdf" /><abstract xml:lang="ru"><p>Background: Gentamicin induces testicular damage in association with oxidative stress explained by different mechanisms, including gene expression suppression of some antioxidant enzymes. The aim of the study: To investigate the potential protective effects of &amp;alpha;-lipoic acid against gentamicin-induced testicular oxidative stress in terms of altered gene expression. Materials and methods: A parallel experimental study was conducted including fifty adult male albino rats. The animals were grouped into five. The control group received intraperitoneal NaCl 0.9%, while the other groups received 36.5mg/kg/day intraperitoneal gentamicin. Group-1 received gentamicin only, group-2 received gentamicin + intraperitoneal &amp;alpha;-lipoic acid 100mg/kg/day, group-3 received gentamicin + intraperitoneal &amp;alpha;-lipoic acid 200mg/kg/day, and group-4 received gentamicin + oral vitamin E 100mg/kg/day. All treatments were given for 14 days. The animals were euthanized in two halves on the 15th and 60th days. Testes were immediately removed, frozen, and evaluated for oxidative stress biomarkers and gene expression of antioxidant enzymes. Results: Gentamicin increased malondialdehyde by mean difference &amp;plusmn; standard error of 115.57 &amp;plusmn; 2.18, decreased total antioxidant capacity by -9.23 &amp;plusmn; 0.27, and decreased catalase and superoxide dismutase activities by -1.89 &amp;plusmn; 0.45 and -11.77 &amp;plusmn; 2.86, respectively, compared to the control. Additionally, gentamicin downregulated gene expression of catalase, glutathione peroxidase, and superoxide dismutase. However, adding vitamin E or &amp;alpha;-lipoic acid cured the oxidative stress and partially to completely upregulated the gene expression. Conclusion: Reversal of testicular oxidative and gene suppression associated with gentamicin could be achieved with &amp;alpha;-lipoic acid co-treatment, which might be applied in human studies</p></abstract><trans-abstract xml:lang="en"><p>Background: Gentamicin induces testicular damage in association with oxidative stress explained by different mechanisms, including gene expression suppression of some antioxidant enzymes. The aim of the study: To investigate the potential protective effects of &amp;alpha;-lipoic acid against gentamicin-induced testicular oxidative stress in terms of altered gene expression. Materials and methods: A parallel experimental study was conducted including fifty adult male albino rats. The animals were grouped into five. The control group received intraperitoneal NaCl 0.9%, while the other groups received 36.5mg/kg/day intraperitoneal gentamicin. Group-1 received gentamicin only, group-2 received gentamicin + intraperitoneal &amp;alpha;-lipoic acid 100mg/kg/day, group-3 received gentamicin + intraperitoneal &amp;alpha;-lipoic acid 200mg/kg/day, and group-4 received gentamicin + oral vitamin E 100mg/kg/day. All treatments were given for 14 days. The animals were euthanized in two halves on the 15th and 60th days. Testes were immediately removed, frozen, and evaluated for oxidative stress biomarkers and gene expression of antioxidant enzymes. Results: Gentamicin increased malondialdehyde by mean difference &amp;plusmn; standard error of 115.57 &amp;plusmn; 2.18, decreased total antioxidant capacity by -9.23 &amp;plusmn; 0.27, and decreased catalase and superoxide dismutase activities by -1.89 &amp;plusmn; 0.45 and -11.77 &amp;plusmn; 2.86, respectively, compared to the control. Additionally, gentamicin downregulated gene expression of catalase, glutathione peroxidase, and superoxide dismutase. However, adding vitamin E or &amp;alpha;-lipoic acid cured the oxidative stress and partially to completely upregulated the gene expression. Conclusion: Reversal of testicular oxidative and gene suppression associated with gentamicin could be achieved with &amp;alpha;-lipoic acid co-treatment, which might be applied in human studies</p></trans-abstract><kwd-group xml:lang="ru"><kwd>Alpha lipoic acid</kwd><kwd>Aminoglycosides</kwd><kwd>Antioxidant genes</kwd><kwd>Testis</kwd></kwd-group><kwd-group xml:lang="en"><kwd>Alpha lipoic acid</kwd><kwd>Aminoglycosides</kwd><kwd>Antioxidant genes</kwd><kwd>Testis</kwd></kwd-group></article-meta></front><back><ack><p>to staff members of the Central Laboratory of the faculty for their help and support.</p></ack><ref-list><title>Список литературы</title><ref id="B1"><mixed-citation>Odabasi IO, Bulbul A. Neonatal sepsis. The Medical Bulletin of Sisli Etfal Hospital. 2020;54(2):142-158. DOI: https://doi.org/10.14744/SEMB.2020.00236</mixed-citation></ref><ref id="B2"><mixed-citation>Ross JDC, Brittain C, Cole M, et al. Gentamicin compared with ceftriaxone for the treatment of gonorrhoea (G-ToG): a randomised non-inferiority trial. The Lancet. 2019;393(10190):2511-2520. DOI: https://doi.org/10.1016/S0140-6736(18)32817-4</mixed-citation></ref><ref id="B3"><mixed-citation>Chaves BJ, Tadi P. Gentamicin. In: StatPearls. StatPearls Publishing, Treasure Island (FL); 2023.</mixed-citation></ref><ref id="B4"><mixed-citation>Laurell G. Pharmacological intervention in the field of ototoxicity. HNO. 2019;67(6):434-439. DOI: https://doi.org/10.1007/s00106-019-0663-1</mixed-citation></ref><ref id="B5"><mixed-citation>Mousavinasab SR, Akhoundi-Meybodi Z, Mahmoudi L, et al. A randomized double-blinded placebo-controlled clinical trial on protective effects of pentoxifylline on gentamicin nephrotoxicity in infectious patients. Clinical and Experimental Nephrology. 2021;25(8):844-853. DOI: https://doi.org/10.1007/s10157-021-02032-9</mixed-citation></ref><ref id="B6"><mixed-citation>Aly HAA. Testicular toxicity of gentamicin in adult rats: Ameliorative effect of lycopene. Human and Experimental Toxicology. 2019;38(11):1302-1313. DOI: https://doi.org/10.1177/0960327119864160</mixed-citation></ref><ref id="B7"><mixed-citation>Gyselynck A-M, Forrey A, Cutler R. Pharmacokinetics of gentamicin: distribution and plasma and renal clearance. Journal of Infectious Diseases. 1971;124(Suppl.1):S70-S76. DOI: https://doi.org/10.1093/infdis/124.Supplement_1.S70</mixed-citation></ref><ref id="B8"><mixed-citation>Yarijani ZM, Najafi H, Shackebaei D, et al. Amelioration of renal and hepatic function, oxidative stress, inflammation and histopathologic damages by Malva sylvestris extract in gentamicin induced renal toxicity. Biomedicine and Pharmacotherapy. 2019;112:108635. DOI: https://doi.org/10.1016/j.biopha.2019.108635</mixed-citation></ref><ref id="B9"><mixed-citation>Morales AI, Detaille D, Prieto M, et al. Metformin prevents experimental gentamicin-induced nephropathy by a mitochondria-dependent pathway. Kidney International. 2010;77(10):861-869. DOI: https://doi.org/10.1038/ki.2010.11</mixed-citation></ref><ref id="B10"><mixed-citation>Lesniak W, Pecoraro VL, Schacht J. Ternary complexes of gentamicin with iron and lipid catalyze formation of reactive oxygen species. Chemical Research in Toxicology. 2005;18(2):357-364. DOI: https://doi.org/10.1021/tx0496946</mixed-citation></ref><ref id="B11"><mixed-citation>Karaman M, Budak H, &amp;Ccedil;iftci M. Amoxicillin and gentamicin antibiotics treatment adversely influence the fertility and morphology through decreasing the Dazl gene expression level and increasing the oxidative stress. Archives of Physiology and Biochemistry. 2019;125(5):447-455. DOI: https://doi.org/10.1080/13813455.2018.1482354</mixed-citation></ref><ref id="B12"><mixed-citation>Babaeenezhad E, Nouryazdan N, Nasri M, et al. Cinnamic acid ameliorate gentamicin-induced liver dysfunctions and nephrotoxicity in rats through induction of antioxidant activities. Heliyon. 2021;7(7):e07465. DOI: https://doi.org/10.1016/j.heliyon.2021.e07465</mixed-citation></ref><ref id="B13"><mixed-citation>El-Azeem A, Nashwa I, Abdel-Sattar SA, et al. Nicorandil ameliorates gentamicin-induced nephrotoxicity through Nrf2/HO-1, p38 MAPK/NF-&amp;kappa;B p65/NO and miR-7/CHOP pathways. Azhar International Journal of Pharmaceutical and Medical Sciences. 2022;3(1):156-171. DOI: https://doi.org/10.21608/AIJPMS.2022.156529.1162</mixed-citation></ref><ref id="B14"><mixed-citation>Lenzi A, Gandini L, Lombardo F, et al. Polyunsaturated fatty acids of germ cell membranes, glutathione and blutathione-dependent enzyme-PHGPx: from basic to clinic. Contraception. 2002;65(4):301-304. DOI: https://doi.org/10.1016/S0010-7824(02)00276-7</mixed-citation></ref><ref id="B15"><mixed-citation>Karna KK, Shin YS, Choi BR, et al. The role of endoplasmic reticulum stress response in male reproductive physiology and pathology: a review. World Journal of Men?s Health. 2020;38(4):484-494. DOI: https://doi.org/10.5534/wjmh.190038</mixed-citation></ref><ref id="B16"><mixed-citation>Elsawah HK, Kandiel MM, Amin AA, et al. Gentamicin and amikacin adversely affect male infertility indicated by pharmacological, andrological and pathological evidence. International Journal of Basic and Clinical Pharmacology. 2020;9(2):218-225. DOI: http://dx.doi.org/10.18203/2319-2003.ijbcp20200167</mixed-citation></ref><ref id="B17"><mixed-citation>Zahedi A, Fathiazad F, Khaki A, et al. Protective effect of ginger on gentamicin-induced apoptosis in testis of rats. Advanced Pharmaceutical Bulletin. 2012;2(2):197-200. DOI: https://doi.org/10.5681/apb.2012.030</mixed-citation></ref><ref id="B18"><mixed-citation>Nouri M, Khaki A, Fathiazar F, et al. The protective effects of carrot seed extract on spermatogenesis and cauda epididymal sperm reserves in gentamicin treated rats. Yakhteh Medical Journal. 2009;11(3):327-333.</mixed-citation></ref><ref id="B19"><mixed-citation>Kim SH, Lee IC, Baek HS, et al. Melatonin prevents gentamicin‐induced testicular toxicity and oxidative stress in rats. Andrologia. 2014;46(9):1032-1040. DOI: https://doi.org/10.1111/and.12191</mixed-citation></ref><ref id="B20"><mixed-citation>&amp;Ouml;m&amp;uuml;r AD, Kandemir FM, Yildirim BA. Protective effect of dandelion (Taraxacum officinale) extract against gentamicin-induced reproductive damage in male rats. Kafkas Universitesi Veteriner Fakultesi Dergisi. 2016;22(6):929-936.</mixed-citation></ref><ref id="B21"><mixed-citation>Yahya K, Hassan AH, Nadhem H. Evaluation the Effect of Gentamicin on Fertility of Male Rats &amp;amp; Probable Protective Role of Lipoic Acid. Indian Journal of Public Health Research and Development. 2019;10(6):1230. DOI: https://doi.org/10.5958/0976-5506.2019.01461.X</mixed-citation></ref><ref id="B22"><mixed-citation>Fetouh FA, Azab AES. Ameliorating effects of curcumin and propolis against the reproductive toxicity of gentamicin in adult male guinea pigs: Quantitative analysis and morphological study. American Journal of Life Sciences. 2014;2(3):138-149. DOI: https://doi.org/10.11648/j.ajls.20140203.13</mixed-citation></ref><ref id="B23"><mixed-citation>Azza SA, Ola AH, Amal R, et al. Omega-3 polyunsaturated fatty acids confer protection against gentamicin-induced testicular injury: Novel insights into possible mechanisms. Journal of Physiology and Pathophysiology. 2019;10(2):17-33. DOI: https://doi.org/10.5897/JPAP2019.0126</mixed-citation></ref><ref id="B24"><mixed-citation>Bukhari AS, Illahi M, Haque AU. Protective Effects of Vitamin C and E in Gentamicin induced Testicular Toxicity in Albino Mice. International Journal of Pathology. 2019;17(4):144-150.</mixed-citation></ref><ref id="B25"><mixed-citation>Hamoud AE. Possible role of selenium nano-particles on gentamicin-induced toxicity in rat testis: morphological and morphometric study. Egyptian Journal of Histology. 2019;42(4):861-873. DOI: https://doi.org/10.21608/ejh.2019.9926.1093</mixed-citation></ref><ref id="B26"><mixed-citation>Bilska A, Wlodek L. Lipoic acid-the drug of the future. Pharmacological Reports. 2005;57(5):570-577.</mixed-citation></ref><ref id="B27"><mixed-citation>Prathima P, Venkaiah K, Pavani R, et al. &amp;alpha;-lipoic acid inhibits oxidative stress in testis and attenuates testicular toxicity in rats exposed to carbimazole during embryonic period. Toxicology Reports. 2017;4:373-381. DOI: https://doi.org/10.1016/j.toxrep.2017.06.009</mixed-citation></ref><ref id="B28"><mixed-citation>Elsawah H, Mokhimar HM, Kandiel MM, et al. The ameliorative effect of &amp;alpha;-lipoic acid on testicular dysfunction induced by gentamicin. Benha Veterinary Medical Journal. 2022;42(2):104-108. DOI: https://doi.org/10.21608/bvmj.2022.139979.1525</mixed-citation></ref><ref id="B29"><mixed-citation>Aramba&amp;scaron;ić J, Mihailović M, Uskoković A, et al. Alpha-lipoic acid upregulates antioxidant enzyme gene expression and enzymatic activity in diabetic rat kidneys through an O-GlcNAc-dependent mechanism. European Journal of Nutrition. 2013;52(5):1461-1473. DOI: https://doi.org/10.1007/s00394-012-0452-z</mixed-citation></ref><ref id="B30"><mixed-citation>Jamor P, Ahmadvand H, Ashoory H, et al. Effect of alpha-lipoic acid on antioxidant gene expression and kidney injury in alloxan-induced diabetic rats. Journal of Nephropathology. 2019;8(1).6-6. DOI: https://doi.org/10.15171/jnp.2019.06</mixed-citation></ref><ref id="B31"><mixed-citation>Paget GE, Barnes JM. Toxicity tests.&amp;nbsp; Evaluation of drug activities: pharmacometrics: ASPET; 1964.</mixed-citation></ref><ref id="B32"><mixed-citation>Garrett NE, Malcangio M, Dewhurst M, et al. &amp;alpha;-Lipoic acid corrects neuropeptide deficits in diabetic rats via induction of trophic support. Neuroscience Letters. 1997;222(3):191-194. DOI: https://doi.org/10.1016/S0304-3940(97)13383-3</mixed-citation></ref><ref id="B33"><mixed-citation>Takaoka M, Kobayashi Y, Yuba M, et al. Effects of &amp;alpha;-lipoic acid on deoxycorticosterone acetate&amp;ndash;salt-induced hypertension in rats. European Journal of Pharmacology. 2001;424(2):121-129. DOI: https://doi.org/10.1016/S0014-2999(01)01120-7</mixed-citation></ref><ref id="B34"><mixed-citation>Upaganlawar A, Gandhi C, Balaraman R. Effect of green tea and vitamin E combination in isoproterenol induced myocardial infarction in rats. Plant Foods for Human Nutrition. 2009;64:75-80. DOI: https://doi.org/10.1007/s11130-008-0105-9</mixed-citation></ref><ref id="B35"><mixed-citation>Gupta K, Hooton TM, Naber KG, et al. International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis and Pyelonephritis in Women: A 2010 Update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clinical Infectious Diseases. 2011;52(5): e103-e120. DOI: https://doi.org/10.1093/cid/ciq257</mixed-citation></ref><ref id="B36"><mixed-citation>Gonder JC, Laber K. A renewed look at laboratory rodent housing and management. ILAR Journal. 2007;48(1):29-36. DOI: https://doi.org/10.1093/ilar.48.1.29</mixed-citation></ref><ref id="B37"><mixed-citation>Nakatsu N, Igarashi Y, Aoshi T, et ap. Isoflurane is a suitable alternative to ether for anesthetizing rats prior to euthanasia for gene expression analysis. Journal of Toxicological Sciences. 2017;42(4):491-497. DOI: https://doi.org/10.2131/jts.42.491</mixed-citation></ref><ref id="B38"><mixed-citation>Shaughnessy P. Age dependent differences in testicular inactivation of FSH and in inhibition of FSH binding to rat testis. Biology of Reproduction. 1979;20(5):1009-1014. DOI: https://doi.org/10.1095/biolreprod20.5.1009</mixed-citation></ref><ref id="B39"><mixed-citation>Aebi H. [13] Catalase in vitro. Methods in Enzymology. 1984;105:121-126. DOI: https://doi.org/10.1016/S0076-6879(84)05016-3</mixed-citation></ref><ref id="B40"><mixed-citation>Wang Z, Zhao D, Chen L, et al. Glycine increases glyoxalase‐1 function by promoting nuclear factor erythroid 2‐related factor 2 translocation into the nucleus of kidney cells of streptozotocin‐induced diabetic rats. Journal of Diabetes Investigation. 2019;10(5):1189-1198. DOI: https://doi.org/10.1111/jdi.13032</mixed-citation></ref><ref id="B41"><mixed-citation>Bryman A, Cramer D. Quantitative data analysis with SPSS 14, 15 &amp;amp; 16: A guide for social scientists. Routledge/Taylor &amp;amp; Francis Group; 2009.</mixed-citation></ref><ref id="B42"><mixed-citation>Abdel-Raheem IT, El-Sherbiny GA, Taye A. Green tea ameliorates renal oxidative damage induced by gentamicin in rats. Pakistan Journal of Pharmaceutical Sciences. 2010;23(1):21-28.</mixed-citation></ref><ref id="B43"><mixed-citation>Ojano-Dirain CP, Antonelli PJ, Le Prell CG. Mitochondria-targeted antioxidant MitoQ reduces gentamicin-induced ototoxicity. Otology and Neurotology. 2014;35(3):533-539. DOI: https://doi.org/10.1097/MAO.0000000000000192</mixed-citation></ref><ref id="B44"><mixed-citation>Aly HAA, Hassan MH. Potential testicular toxicity of gentamicin in adult rats. Biochemical and Biophysical Research Communications. 2018;497(1):362-367. DOI: https://doi.org/10.1016/j.bbrc.2018.02.085</mixed-citation></ref><ref id="B45"><mixed-citation>Akondi RB, Annapurna A. Protective effects of rutin and naringin on gentamycin induced testicular oxidative stress. European Journal of General Medicine. 2011;8(1):57-64.</mixed-citation></ref><ref id="B46"><mixed-citation>Narayana K. An aminoglycoside antibiotic gentamycin induces oxidative stress, reduces antioxidant reserve and impairs spermatogenesis in rats. Journal of Toxicological Sciences. 2008;33(1):85-96. DOI: https://doi.org/10.2131/jts.33.85</mixed-citation></ref><ref id="B47"><mixed-citation>Tahira A, Saleem U, Mahmood S, et al. Evaluation of protective and curative role of &amp;alpha;-lipoic acid and selenium in gentamicin-induced nephrotoxicity in rabbits. Pakistan Journal of Pharmaceutical Sciences. 2012;25(1):103-110.</mixed-citation></ref><ref id="B48"><mixed-citation>Kaplan HM, Şingirik E, Erdoğan KE, et al. Protective effect of alpha-linolenic acid on gentamicin-induced ototoxicity in mice. Somatosensory and Motor Research. 2017;34(3):145-150. DOI: https://doi.org/10.1080/08990220.2017.1356283</mixed-citation></ref><ref id="B49"><mixed-citation>Bhatti F, Mankhey RW, Asico L, et al. Mechanisms of antioxidant and pro-oxidant effects of &amp;alpha;-lipoic acid in the diabetic and nondiabetic kidney. Kidney International. 2005;67(4):1371-1380. DOI: https://doi.org/10.1111/j.1523-1755.2005.00214.x</mixed-citation></ref><ref id="B50"><mixed-citation>Ou P, Tritschler HJ, Wolff SP. Thioctic (lipoic) acid: a therapeutic metal-chelating antioxidant? Biochemical Pharmacology. 1995;50(1):123-126. DOI: https://doi.org/10.1016/0006-2952(95)00116-H</mixed-citation></ref><ref id="B51"><mixed-citation>Rochette L, Ghibu S, Richard C, et al. Direct and indirect antioxidant properties of &amp;alpha;‐lipoic acid and therapeutic potential. Molecular Nutrition and Food Research. 2013;57(1):114-125. DOI: https://doi.org/10.1002/mnfr.201200608</mixed-citation></ref><ref id="B52"><mixed-citation>Patel Manali B, Deshpande S, Shah G. Evaluation of efficacy of vitamin E and N-acetyl cysteine in gentamicin-induced nephrotoxicity in rats. Renal Failure. 2011;33(3):341-347. DOI: https://doi.org/10.3109/0886022X.2011.560987</mixed-citation></ref><ref id="B53"><mixed-citation>Kadkhodaee M, Khastar H, Faghihi M, et al. Effects of co‐supplementation of vitamins E and C on gentamicin‐induced nephrotoxicity in rat. Experimental Physiology. 2005;90(4):571-576. DOI: https://doi.org/10.1113/expphysiol.2004.029728</mixed-citation></ref><ref id="B54"><mixed-citation>Yamauchi R. Vitamin E: mechanism of its antioxidant activity. Food Science and Technology International. 1997;3(4):301-309. DOI: https://doi.org/10.3136/fsti9596t9798.3.301</mixed-citation></ref><ref id="B55"><mixed-citation>Badgujar PC, Chandratre GA, Pawar NN, et al. Fipronil induced oxidative stress involves alterations in SOD 1 and catalase gene expression in male mice liver: Protection by vitamins E and C. Environmental Toxicology. 2016;31(9):1147-1158. DOI: https://doi.org/10.1002/tox.22125</mixed-citation></ref></ref-list></back></article>