{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T11:20:57Z","timestamp":1776856857808,"version":"3.51.2"},"reference-count":73,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,8,20]],"date-time":"2020-08-20T00:00:00Z","timestamp":1597881600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Background: Sodium valproate (VPA) is an antiepileptic drug (AED) licensed for epilepsy and used during pregnancy in various indications. Alpha-lipoic acid (ALA) is a natural compound inducing endogenous antioxidant production. Our study aimed to investigate the effect of prenatal administration of VPA on the pancreas of rat offspring and assess the potential protective role of ALA co-administration during pregnancy. Methods: Twenty-eight pregnant female albino rats were divided into four groups: group I (negative control), group II (positive control, ALA treated), group III (VPA-treated), and group IV (VPA-ALA-treated). The pancreases of the rat offspring were removed at the fourth week postpartum and prepared for histological, immune-histochemical, morphometric, molecular, and oxidative stress marker studies. Results: In group III, there were pyknotic nuclei, vacuolated cytoplasm with ballooning of acinar, \u03b1, and \u03b2 cells of the pancreas. Ultrastructural degeneration of cytoplasmic organelles was detected. Additionally, there was a significant increase in oxidative stress, a decrease in insulin-positive cell percentage, and an increase in glucagon positive cells in comparison to control groups. Moreover, VPA increased the gene expression of an apoptotic marker, caspase-3, with a decrease in anti-apoptotic Bcl2 and nuclear factor erythroid 2-related factor 2 (Nrf2) transcriptional factor. Conversely, ALA improved oxidative stress and apoptosis in group VI, and a consequent improvement of the histological and ultrastructure picture was detected. Conclusion: ALA co-administration with VPA significantly improved the oxidative stress condition, histological and morphometric picture of the pancreas, and restored normal expression of related genes, including Nrf2, caspase-3, and Bcl-2. Administration of \u03b1-lipoic acid has a protective effect against VPA-induced pancreatic oxidative damage via its cytoprotective antioxidant effect.<\/jats:p>","DOI":"10.3390\/biology9090239","type":"journal-article","created":{"date-parts":[[2020,8,20]],"date-time":"2020-08-20T09:35:31Z","timestamp":1597916131000},"page":"239","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["The Protective Role of Prenatal Alpha Lipoic Acid Supplementation against Pancreatic Oxidative Damage in Offspring of Valproic Acid-Treated Rats: Histological and Molecular Study"],"prefix":"10.3390","volume":"9","author":[{"given":"Fatma M.","family":"Ghoneim","sequence":"first","affiliation":[{"name":"Histology and Cell Biology Department, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2687-6487","authenticated-orcid":false,"given":"Hani","family":"Alrefai","sequence":"additional","affiliation":[{"name":"Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt"},{"name":"Department of Internal Medicine, Infectious Diseases Div., College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8731-6184","authenticated-orcid":false,"given":"Ayman Z.","family":"Elsamanoudy","sequence":"additional","affiliation":[{"name":"Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt"},{"name":"Clinical Biochemistry Department, Faculty of Medicine, King Abdulaziz University, Jeddah 21465, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5449-2723","authenticated-orcid":false,"given":"Salwa M.","family":"Abo El-khair","sequence":"additional","affiliation":[{"name":"Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanaa A.","family":"Khalaf","sequence":"additional","affiliation":[{"name":"Histology and Cell Biology Department, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1684\/j.1950-6945.2004.tb00053.x","article-title":"Antiepileptic drugs: Indications other than epilepsy","volume":"6","author":"Spina","year":"2004","journal-title":"Epileptic Disord."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e017248","DOI":"10.1136\/bmjopen-2017-017248","article-title":"Comparative safety of antiepileptic drugs for neurological development in children exposed during pregnancy and breast feeding: A systematic review and network meta-analysis","volume":"7","author":"Veroniki","year":"2017","journal-title":"BMJ Open"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Macfarlane, A., and Greenhalgh, T. (2018). Sodium valproate in pregnancy: What are the risks and should we use a shared decision-making approach?. BMC Pregnancy Childbirth, 18.","DOI":"10.1186\/s12884-018-1842-x"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"k1609","DOI":"10.1136\/bmj.k1609","article-title":"Dangers of valproate in pregnancy","volume":"361","author":"Wieck","year":"2018","journal-title":"BMJ"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1111\/j.1528-1167.2009.02130.x","article-title":"Management issues for women with epilepsy-Focus on pregnancy (an evidence-based review): III. Vitamin K, folWic acid, blood levels, and breast-feeding","volume":"50","author":"Harden","year":"2009","journal-title":"Epilepsia"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"95","DOI":"10.2147\/CLEP.S118336","article-title":"Antiepileptic drugs prescribed in pregnancy and prevalence of major congenital malformations: Comparative prevalence studies","volume":"9","author":"Petersen","year":"2017","journal-title":"Clin. Epidemiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1089\/aivt.2015.0016","article-title":"Valproate Disturbs Morphology and Mitochondrial Membrane Potential in Human Neural Cells","volume":"1","author":"Kormann","year":"2015","journal-title":"Appl. In Vitro Toxicol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"173","DOI":"10.5487\/TR.2018.34.2.173","article-title":"Valproic Acid Exposure of Pregnant Rats During Organogenesis Disturbs Pancreas Development in Insulin Synthesis and Secretion of the Offspring","volume":"34","author":"Komariah","year":"2018","journal-title":"Toxicol. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2058738418785514","DOI":"10.1177\/2058738418785514","article-title":"Leptin and camel milk abate oxidative stress status, genotoxicity induced in valproic acid rat model of autism","volume":"32","author":"Hamzawy","year":"2018","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"421","DOI":"10.4103\/psychiatry.IndianJPsychiatry_383_18","article-title":"Valproic acid-induced acute pancreatitis","volume":"61","author":"Jain","year":"2019","journal-title":"Indian J. Psychiatry"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"349","DOI":"10.3325\/cmj.2017.58.349","article-title":"The role and possible molecular mechanism of valproic acid in the growth of MCF-7 breast cancer cells","volume":"58","author":"Ma","year":"2017","journal-title":"Croat. Med. J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4093018","DOI":"10.1155\/2019\/4093018","article-title":"Alpha Lipoic Acid Improves Endothelial Function and Oxidative Stress in Mice Exposed to Chronic Intermittent Hypoxia","volume":"2019","author":"Badran","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2761","DOI":"10.3748\/wjg.v19.i18.2761","article-title":"Lipoic acid suppresses portal endotoxemia-induced steatohepatitis and pancreatic inflammation in rats","volume":"19","author":"Tian","year":"2013","journal-title":"World J. Gastroenterol."},{"key":"ref_14","first-page":"4219","article-title":"Safety of oral alpha-lipoic acid treatment in pregnant women: A retrospective observational study","volume":"21","author":"Parente","year":"2017","journal-title":"Eur. Rev. Med. Pharmacol."},{"key":"ref_15","first-page":"8135610","article-title":"Corrigendum to \u201cEffects of Lipoic Acid Supplementation on Activities of Cyclooxygenases and Levels of Prostaglandins E2 and F2alpha Metabolites, in the Offspring of Rats with Streptozotocin-Induced Diabetes\u201d","volume":"2017","author":"Oriquat","year":"2017","journal-title":"J. Diabetes Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/sj.npp.1300767","article-title":"Environmental enrichment reverses behavioral alterations in rats prenatally exposed to valproic acid: Issues for a therapeutic approach in autism","volume":"31","author":"Schneider","year":"2006","journal-title":"Neuropsychopharmacol. Off. Publ. Am. Coll. Neuropsychopharmacol."},{"key":"ref_17","unstructured":"Suvarna, S.K., Layton, C., and Bancroft, J.D. (2019). 10\u2014The hematoxylins and eosin. Bancroft\u2019s Theory and Practice of Histological Techniques, Content Repository Only; Elsevier Health Science. [8th ed.]."},{"key":"ref_18","first-page":"43","article-title":"Chapter Two\u2014Transmission Electron Microscopy: Emerging Investigations for Cultural Heritage Materials","volume":"Volume 198","author":"Hawkes","year":"2016","journal-title":"Advances in Imaging and Electron Physics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1007\/s11418-008-0228-1","article-title":"Antihyperglycemic and antioxidative potential of Matricaria chamomilla L. in streptozotocin-induced diabetic rats","volume":"62","author":"Cemek","year":"2008","journal-title":"J. Nat. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/0891-5849(93)90035-S","article-title":"A comparative evaluation of thiobarbituric acid methods for the determination of malondialdehyde in biological materials","volume":"15","author":"Draper","year":"1993","journal-title":"Free Radic. Biol. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1136\/jcp.54.5.356","article-title":"Method for the measurement of antioxidant activity in human fluids","volume":"54","author":"Koracevic","year":"2001","journal-title":"J. Clin. Pathol."},{"key":"ref_22","unstructured":"Koroliuk, M.A., Ivanova, L.I., Maiorova, I.G., and Tokarev, V.E. (1988). A method of determining catalase activity. Lab. Delo, 16\u201319."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/S0076-6879(81)77046-0","article-title":"Glutathione peroxidase","volume":"Volume 77","author":"Wendel","year":"1981","journal-title":"Methods in Enzymology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1093\/clinchem\/34.3.497","article-title":"A Simple Method for Clinical Assay of Superoxide-Dismutase","volume":"34","author":"Sun","year":"1988","journal-title":"Clin. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Yamashita, Y., Ueyama, T., Nishi, T., Yamamoto, Y., Kawakoshi, A., Sunami, S., Iguchi, M., Tamai, H., Ueda, K., and Ito, T. (2014). Nrf2-inducing anti-oxidation stress response in the rat liver\u2014New beneficial effect of lansoprazole. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0097419"},{"key":"ref_26","first-page":"873","article-title":"Expression of caspase-3, Bax and Bcl-2 in hippocampus of rats with diabetes and subarachnoid hemorrhage","volume":"15","author":"He","year":"2018","journal-title":"Exp. Ther. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"364","DOI":"10.3390\/ijerph7020364","article-title":"Alcohol Abuse in Pregnant Women: Effects on the Fetus and Newborn, Mode of Action and Maternal Treatment","volume":"7","author":"Ornoy","year":"2010","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1930261","DOI":"10.1155\/2017\/1930261","article-title":"Oxidative Stress in Pancreatic Beta Cell Regeneration","volume":"2017","author":"Wang","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1111\/dgd.12237","article-title":"Development of the pancreas in medaka, Oryzias latipes, from embryo to adult","volume":"57","author":"Otsuka","year":"2015","journal-title":"Dev. Growth Differ."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.apsb.2012.06.005","article-title":"Histone deacetylases and their inhibitors: Molecular mechanisms and therapeutic implications in diabetes mellitus","volume":"2","author":"Wang","year":"2012","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1111\/aogs.12495","article-title":"Co-ordinated regulation of neurogenin-3 expression in the maternal and fetal pancreas during pregnancy","volume":"93","author":"Sostrup","year":"2014","journal-title":"Acta Obstet. Gyn. Scan"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Gomez, D.L., O\u2019Driscoll, M., Sheets, T.P., Hruban, R.H., Oberholzer, J., McGarrigle, J.J., and Shamblott, M.J. (2015). Neurogenin 3 Expressing Cells in the Human Exocrine Pancreas Have the Capacity for Endocrine Cell Fate. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0133862"},{"key":"ref_33","first-page":"226","article-title":"MiRNAs in beta-Cell Development, Identity, and Disease","volume":"7","author":"Rutter","year":"2016","journal-title":"Front. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"113","DOI":"10.2165\/00148581-200608020-00004","article-title":"Valproate as a Mainstay of Therapy for Pediatric Epilepsy","volume":"8","author":"Guerrini","year":"2006","journal-title":"Pediatr. Drugs"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"89","DOI":"10.3390\/toxics3010089","article-title":"Multifactorial Origin of Neurodevelopmental Disorders: Approaches to Understanding Complex Etiologies","volume":"3","author":"Ricceri","year":"2015","journal-title":"Toxics"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"89","DOI":"10.18203\/2320-1770.ijrcog20164638","article-title":"Study of congenital malformation in tertiary care centre, Mumbai, Maharashtra, India","volume":"6","author":"Kokate","year":"2017","journal-title":"Int. J. Reprod. Contracept. Obstet. Gynecol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1002\/ajmg.c.30314","article-title":"Genetic basis of susceptibility to teratogen induced birth defects","volume":"157","author":"Wlodarczyk","year":"2011","journal-title":"Am. J. Med. Genet. Part C Semin. Med. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1038\/nrm3629","article-title":"Control of cell cycle transcription during G1 and S phases","volume":"14","author":"Bertoli","year":"2013","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"7207","DOI":"10.1038\/srep07207","article-title":"Effects of histone deacetylase inhibitor valproic acid on skeletal myocyte development","volume":"4","author":"Li","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2935","DOI":"10.3390\/biom5042935","article-title":"The RNA Splicing Response to DNA Damage","volume":"5","author":"Shkreta","year":"2015","journal-title":"Biomolecules"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.exer.2014.01.021","article-title":"Valproic acid suppresses Nrf2\/Keap1 dependent antioxidant protection through induction of endoplasmic reticulum stress and Keap1 promoter DNA demethylation in human lens epithelial cells","volume":"121","author":"Palsamy","year":"2014","journal-title":"Exp. Eye Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1124\/mol.105.017855","article-title":"Valproic acid increases conservative homologous recombination frequency and reactive oxygen species formation: A potential mechanism for valproic acid-induced neural tube defects","volume":"69","author":"Defoort","year":"2006","journal-title":"Mol. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"6563","DOI":"10.1158\/0008-5472.CAN-06-0814","article-title":"Valproic acid-induced gene expression through production of reactive oxygen species","volume":"66","author":"Kawai","year":"2006","journal-title":"Cancer Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/j.acthis.2019.08.002","article-title":"The possible neuroprotective role of grape seed extract on the histopathological changes of the cerebellar cortex of rats prenatally exposed to Valproic Acid: Animal model of autism","volume":"121","author":"Arafat","year":"2019","journal-title":"Acta Histochem."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Ornoy, A., Weinstein-Fudim, L., and Ergaz, Z. (2019). Prevention or Amelioration of Autism-Like Symptoms in Animal Models: Will it Bring Us Closer to Treating Human ASD?. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20051074"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"7954371","DOI":"10.1155\/2018\/7954371","article-title":"Effects of Valproate Monotherapy on the Oxidant-Antioxidant Status in Mexican Epileptic Children: A Longitudinal Study","volume":"2018","year":"2018","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"117","DOI":"10.3389\/fnmol.2018.00117","article-title":"Valproic Acid Attenuates Traumatic Brain Injury-Induced Inflammation in Vivo: Involvement of Autophagy and the Nrf2\/ARE Signaling Pathway","volume":"11","author":"Chen","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"44769","DOI":"10.1038\/srep44769","article-title":"Protection against oxidative stress mediated by the Nrf2\/Keap1 axis is impaired in Primary Biliary Cholangitis","volume":"7","author":"Wasik","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Zhang, X.S., Wu, Q., Wu, L.Y., Ye, Z.N., Jiang, T.W., Li, W., Zhuang, Z., Zhou, M.L., Zhang, X., and Hang, C.H. (2016). Sirtuin 1 activation protects against early brain injury after experimental subarachnoid hemorrhage in rats. Cell Death Dis., 7.","DOI":"10.1038\/cddis.2016.292"},{"key":"ref_50","first-page":"619","article-title":"Synergistic induction of apoptosis in a cell model of human leukemia K562 by nitroglycerine and valproic acid","volume":"18","author":"Aalaei","year":"2019","journal-title":"EXCLI J."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.biopha.2018.10.088","article-title":"The impact of Keap1\/Nrf2, P38MAPK\/NF-\u03baB and Bax\/Bcl2\/caspase-3 signaling pathways in the protective effects of berberine against methotrexate-induced nephrotoxicity","volume":"109","author":"Hassanein","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"171","DOI":"10.3989\/scimar.2009.73s1171","article-title":"Tissue effect on RNA:DNA ratios of marine fish larvae","volume":"73","author":"Olivar","year":"2009","journal-title":"Sci. Mar."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"570","DOI":"10.12991\/marupj.319312","article-title":"Investigation of the Effects of Edaravone on Valproic Acid Induced Tissue Damage in Pancreas","volume":"21","author":"Oktay","year":"2017","journal-title":"Marmara Pharm. J."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/j.sjbs.2016.10.021","article-title":"Protective effects of fennel oil extract against sodium valproate-induced hepatorenal damage in albino rats","volume":"24","year":"2017","journal-title":"Saudi J. Biol. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"285","DOI":"10.21608\/ejh.2019.6198.1040","article-title":"The Possible Protective Role of Methionine against Sodium Fluoride-Induced Pancreatic Changes in the Adult Male Albino Rat: A Histological, Immunohistochemical and Morphometric Study","volume":"42","author":"Zaghloul","year":"2019","journal-title":"Egypt. J. Histol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"E6166","DOI":"10.1073\/pnas.1519384112","article-title":"Basal autophagy maintains pancreatic acinar cell homeostasis and protein synthesis and prevents ER stress","volume":"112","author":"Antonucci","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.jobaz.2013.07.003","article-title":"Protective effect of curcumin on histopathology and ultrastructure of pancreas in the alloxan treated rats for induction of diabetes","volume":"66","author":"Moustafa","year":"2013","journal-title":"J. Basic Appl. Zool."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Salehi, B., Berkay Y\u0131lmaz, Y., Antika, G., Boyunegmez Tumer, T., Fawzi Mahomoodally, M., Lobine, D., Akram, M., Riaz, M., Capanoglu, E., and Sharopov, F. (2019). Insights on the Use of \u03b1-Lipoic Acid for Therapeutic Purposes. Biomolecules, 9.","DOI":"10.3390\/biom9080356"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/S1734-1140(11)70600-4","article-title":"Lipoic acid\u2013biological activity and therapeutic potential","volume":"63","author":"Piechota","year":"2011","journal-title":"Pharmacol. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1016\/j.bbagen.2009.07.026","article-title":"Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential","volume":"1790","author":"Shay","year":"2009","journal-title":"BBA-Gen. Subj."},{"key":"ref_61","first-page":"3276958","article-title":"The Effect of 600 mg Alpha-lipoic Acid Supplementation on Oxidative Stress, Inflammation, and RAGE in Older Adults with Type 2 Diabetes Mellitus","volume":"2019","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1159\/000356145","article-title":"Does Lipoic Acid Consumption Affect the Cytokine Profile in Multiple Sclerosis Patients: A Double-Blind, PlaceboControlled, Randomized Clinical Trial","volume":"21","author":"Khalili","year":"2014","journal-title":"Neuroimmunomodulation"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1039\/C5TX00496A","article-title":"Pancreatic damage induced by cigarette smoke: The specific pathological effects of cigarette smoke in the rat model","volume":"5","author":"Topsakal","year":"2016","journal-title":"Toxicol. Res. UK"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2243","DOI":"10.1080\/14767058.2016.1245282","article-title":"Vaginal alpha-lipoic acid shows an anti-inflammatory effect on the cervix, preventing its shortening after primary tocolysis. A pilot, randomized, placebo-controlled study","volume":"30","author":"Grandi","year":"2017","journal-title":"J. Matern-Fetal Neonatal Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1039\/C8FO01856A","article-title":"Alpha-lipoic acid and its protective role in fructose induced endocrine-metabolic disturbances","volume":"10","author":"Castro","year":"2019","journal-title":"Food Funct."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4088","DOI":"10.1111\/jcmm.14296","article-title":"Alpha lipoic acid inhibits oxidative stress-induced apoptosis by modulating of Nrf2 signalling pathway after traumatic brain injury","volume":"23","author":"Xia","year":"2019","journal-title":"J. Cell. Mol. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1007\/s10495-005-1901-4","article-title":"Evidence for a non-antioxidant, dose-dependent role of alpha-lipoic acid in caspase-3 and ERK2 activation in endothelial cells","volume":"10","author":"Marsh","year":"2005","journal-title":"Apoptosis"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"108679","DOI":"10.1016\/j.biopha.2019.108679","article-title":"Alpha-lipoic acid attenuates p-cresyl sulfate-induced renal tubular injury through suppression of apoptosis and autophagy in human proximal tubular epithelial cells","volume":"112","author":"Park","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S0076-6879(10)74010-6","article-title":"Redox clamp model for study of extracellular thiols and disulfides in redox signaling","volume":"474","author":"Go","year":"2010","journal-title":"Methods Enzymol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/0891-5849(95)00017-R","article-title":"Alpha-Lipoic Acid as a Biological Antioxidant","volume":"19","author":"Packer","year":"1995","journal-title":"Free Radic. Biol. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1111\/j.1753-0407.2012.00195.x","article-title":"Maternal antioxidants prevent beta-cell apoptosis and promote formation of dual hormone-expressing endocrine cells in male offspring following fetal and neonatal nicotine exposure","volume":"4","author":"Bruin","year":"2012","journal-title":"J. Diabetes"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Cappellani, D., Sardella, C., Campopiano, M.C., Falorni, A., Marchetti, P., and Macchia, E. (2018). Spontaneously remitting insulin autoimmune syndrome in a patient taking alpha-lipoic acid. Endocrinol. Diabetes Metab. Case Rep., 2018.","DOI":"10.1530\/EDM-18-0122"},{"key":"ref_73","first-page":"179","article-title":"Effect of Alpha Lipoic Acid in the Treatment of Multiple Sclerosis-Induced Neuropathic Pain: A Case Report","volume":"2","author":"Kulakli","year":"2018","journal-title":"Eurasian J. Med. Oncol."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/9\/9\/239\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:04:09Z","timestamp":1760177049000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/9\/9\/239"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,20]]},"references-count":73,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["biology9090239"],"URL":"https:\/\/doi.org\/10.3390\/biology9090239","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,20]]}}}