{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T14:37:15Z","timestamp":1791383835216,"version":"4.3.3"},"reference-count":42,"publisher":"Japanese Association for Laboratory Animal Science","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Exp. Anim."],"published-print":{"date-parts":[[2021]]},"DOI":"10.1538\/expanim.20-0075","type":"journal-article","created":{"date-parts":[[2020,9,20]],"date-time":"2020-09-20T22:06:25Z","timestamp":1600639585000},"page":"54-62","source":"Crossref","is-referenced-by-count":22,"title":["The potential protective role of folic acid against acetaminophen-induced          hepatotoxicity and nephrotoxicity in rats"],"prefix":"10.1538","volume":"70","author":[{"given":"Emrah","family":"Akgun","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of              Veterinary Medicine, Aydin Adnan Menderes University, Isikli, 09016, Aydin,              Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murat","family":"Boyacioglu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of              Veterinary Medicine, Aydin Adnan Menderes University, Isikli, 09016, Aydin,              Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadiye","family":"Kum","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of              Veterinary Medicine, Aydin Adnan Menderes University, Isikli, 09016, Aydin,              Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"439","reference":[{"key":"1","doi-asserted-by":"crossref","unstructured":"1. Waring              WS, Jamie              H, Leggett              GE. Delayed            onset of acute renal failure after significant paracetamol overdose: A case            series. Hum Exp Toxicol. 2010;            29: 63\u201368.","DOI":"10.1177\/0960327109350799"},{"key":"2","doi-asserted-by":"crossref","unstructured":"2. Guggenheimer              J, Moore              PA. The            therapeutic applications of and risks associated with acetaminophen use: a review and            update. J Am Dent Assoc. 2011;            142: 38\u201344.","DOI":"10.14219\/jada.archive.2011.0026"},{"key":"3","doi-asserted-by":"crossref","unstructured":"3. Chiew              AL, Isbister              GK, Kirby              KA, Page              CB, Chan              BSH, Buckley              NA. Massive            paracetamol overdose: an observational study of the effect of activated charcoal and            increased acetylcysteine dose (ATOM-2). Clin Toxicol            (Phila). 2017; 55:            1055\u20131065.","DOI":"10.1080\/15563650.2017.1334915"},{"key":"4","doi-asserted-by":"crossref","unstructured":"4. Marks              DJB, Dargan              PI, Archer              JRH, Davies              CL, Dines              AM, Wood              DM, et            al. Outcomes from massive paracetamol overdose: a            retrospective observational study. Br J Clin Pharmacol.            2017; 83: 1263\u20131272.","DOI":"10.1111\/bcp.13214"},{"key":"5","doi-asserted-by":"crossref","unstructured":"5. Salmonson              H, Sj\u00f6berg              G, Brogren              J. The standard            treatment protocol for paracetamol poisoning may be inadequate following overdose with            modified release formulation: a pharmacokinetic and clinical analysis of 53            cases. Clin Toxicol (Phila). 2018;            56: 63\u201368.","DOI":"10.1080\/15563650.2017.1339887"},{"key":"6","doi-asserted-by":"crossref","unstructured":"6. Moyer              AM, Fridley              BL, Jenkins              GD, Batzler              AJ,                Pelleymounter              LL, Kalari              KR, et            al. Acetaminophen-NAPQI hepatotoxicity: a cell line            model system genome-wide association study. Toxicol          Sci. 2011; 120:          33\u201341.","DOI":"10.1093\/toxsci\/kfq375"},{"key":"7","doi-asserted-by":"crossref","unstructured":"7. Bessems              JGM,                Vermeulen              NPE.            Paracetamol (acetaminophen)-induced toxicity: molecular and biochemical            mechanisms, analogues and protective approaches. Crit Rev            Toxicol. 2001; 31:            55\u2013138.","DOI":"10.1080\/20014091111677"},{"key":"8","doi-asserted-by":"crossref","unstructured":"8. Parikh              H, Pandita              N, Khanna              A. Phytoextract            of Indian mustard seeds acts by suppressing the generation of ROS against            acetaminophen-induced hepatotoxicity in HepG2 cells. Pharm            Biol. 2015; 53:            975\u2013984.","DOI":"10.3109\/13880209.2014.950675"},{"key":"9","doi-asserted-by":"crossref","unstructured":"9. McGill              MR, Sharpe              MR, Williams              CD, Taha              M, Curry              SC, Jaeschke              H. The            mechanism underlying acetaminophen-induced hepatotoxicity in humans and mice involves            mitochondrial damage and nuclear DNA fragmentation. J Clin            Invest. 2012; 122:            1574\u20131583.","DOI":"10.1172\/JCI59755"},{"key":"10","doi-asserted-by":"crossref","unstructured":"10. Halliwell              B, Gutteridge              JMC. Lipid            peroxidation, oxygen radicals, cell damage, and antioxidant therapy.            Lancet. 1984; 323:            1396\u20131397.","DOI":"10.1016\/S0140-6736(84)91886-5"},{"key":"11","doi-asserted-by":"crossref","unstructured":"13. Dallak              M, Dawood              AF, Haidara              MA, Abdel                Kader              DH, Eid              RA, Kamar              SS, et            al. Suppression of glomerular damage and apoptosis            and biomarkers of acute kidney injury induced by acetaminophen toxicity using a            combination of resveratrol and quercetin. Drug Chem            Toxicol. 2020; 0:            1\u20137.","DOI":"10.1080\/01480545.2020.1722156"},{"key":"12","doi-asserted-by":"crossref","unstructured":"14. Akbar              S, Anwar              A, Kanwal              Q.            Electrochemical determination of folic acid: A short            review. Anal Biochem. 2016;            510: 98\u2013105.","DOI":"10.1016\/j.ab.2016.07.002"},{"key":"13","doi-asserted-by":"crossref","unstructured":"15. Mohammadi              A, Omrani              L, Omrani              LR, Kiani              F, Eshraghian              A, Azizi              Z, et            al. Protective effect of folic acid on            cyclosporine-induced bone loss in rats. Transpl Int.            2012; 25: 127\u2013133.","DOI":"10.1111\/j.1432-2277.2011.01375.x"},{"key":"14","doi-asserted-by":"crossref","unstructured":"16. Singh              R, Kanwar              SS, Sood              PK, Nehru              B. Beneficial            effects of folic acid on enhancement of memory and antioxidant status in aged rat            brain. Cell Mol Neurobiol. 2011;            31: 83\u201391.","DOI":"10.1007\/s10571-010-9557-1"},{"key":"15","doi-asserted-by":"crossref","unstructured":"17. Lai              KG, Chen              CF, Ho              CT, Liu              JJ, Liu              TZ, Chern              CL. Novel roles            of folic acid as redox regulator: Modulation of reactive oxygen species sinker protein            expression and maintenance of mitochondrial redox homeostasis on hepatocellular            carcinoma. Tumour Biol. 2017;            39: 1010428317702649.","DOI":"10.1177\/1010428317702649"},{"key":"16","doi-asserted-by":"crossref","unstructured":"18. Al-Sowyan              NS. Efficacy            and safety of folic acid during toxic hepatitis induced by acute overdose of            paracetamol. Int J Pharmacol. 2009;            5: 208\u2013214.","DOI":"10.3923\/ijp.2009.208.214"},{"key":"17","doi-asserted-by":"crossref","unstructured":"19. Saravanan              T,                Shanmugapriya              S, Sumitra              G, Dhayananth              RS, Saravanan              A, Manicka                Vasuki              AK.            Hepato-protective effect of folic acid and vitamin B12 in comparison to            n-acetylcysteine in experimentally induced acetaminophen toxicity in            rats. Biomed Pharmacol J. 2017;            10: 549\u2013555.","DOI":"10.13005\/bpj\/1140"},{"key":"18","doi-asserted-by":"crossref","unstructured":"20. Kilkenny              C, Browne              WJ, Cuthill              IC, Emerson              M, Altman              DG. Improving            bioscience research reporting: the ARRIVE guidelines for reporting animal            research. PLoS Biol. 2010;            8: e1000412.","DOI":"10.1371\/journal.pbio.1000412"},{"key":"19","doi-asserted-by":"crossref","unstructured":"21. Yousef              MI, Omar              SAM,                El-Guendi              MI,                Abdelmegid              LA. Potential            protective effects of quercetin and curcumin on paracetamol-induced histological            changes, oxidative stress, impaired liver and kidney functions and haematotoxicity in            rat. Food Chem Toxicol. 2010;            48: 3246\u20133261.","DOI":"10.1016\/j.fct.2010.08.034"},{"key":"20","doi-asserted-by":"crossref","unstructured":"22. Sudheesh              NP, Ajith              TA,                Janardhanan              KK.            Hepatoprotective effects of DL-\u03b1-lipoic acid and \u03b1-Tocopherol through            amelioration of the mitochondrial oxidative stress in acetaminophen challenged            rats. Toxicol Mech Methods. 2013;            23: 368\u2013376.","DOI":"10.3109\/15376516.2013.769289"},{"key":"21","doi-asserted-by":"crossref","unstructured":"23. Mahmoud              YI, Mahmoud              AA. Role of            nicotinamide (vitamin B3) in acetaminophen-induced changes in rat liver: Nicotinamide            effect in acetaminophen-damged liver. Exp Toxicol            Pathol. 2016; 68:            345\u2013354.","DOI":"10.1016\/j.etp.2016.05.003"},{"key":"22","doi-asserted-by":"crossref","unstructured":"24. Sun              Y, Oberley              LW, Li              Y. A simple            method for clinical assay of superoxide dismutase. Clin            Chem. 1988; 34:            497\u2013500.","DOI":"10.1093\/clinchem\/34.3.497"},{"key":"23","doi-asserted-by":"crossref","unstructured":"25. Aebi              H. Catalase in            vitro. Methods Enzymol. 1984;            105: 121\u2013126.","DOI":"10.1016\/S0076-6879(84)05016-3"},{"key":"24","doi-asserted-by":"crossref","unstructured":"26. Tietze              F. Enzymic            method for quantitative determination of nanogram amounts of total and oxidized            glutathione: applications to mammalian blood and other tissues.            Anal Biochem. 1969; 27:            502\u2013522.","DOI":"10.1016\/0003-2697(69)90064-5"},{"key":"25","doi-asserted-by":"crossref","unstructured":"27. Ohkawa              H, Ohishi              N, Yagi              K. Assay for            lipid peroxides in animal tissues by thiobarbituric acid reaction.            Anal Biochem. 1979; 95:            351\u2013358.","DOI":"10.1016\/0003-2697(79)90738-3"},{"key":"26","doi-asserted-by":"crossref","unstructured":"28. Bradley              PP, Priebat              DA,                Christensen              RD, Rothstein              G. Measurement            of cutaneous inflammation: estimation of neutrophil content with an enzyme            marker. J Invest Dermatol. 1982;            78: 206\u2013209.","DOI":"10.1111\/1523-1747.ep12506462"},{"key":"27","doi-asserted-by":"crossref","unstructured":"29. Crossmon              G. A            modification of Mallory\u2019s connective tissue stain with a discussion of the principles            involved. Anat Rec. 1937;            69: 33\u201338.","DOI":"10.1002\/ar.1090690105"},{"key":"28","doi-asserted-by":"publisher","unstructured":"30. Abdel-Zaher              AO,                Abdel-Hady              RH, Mahmoud              MM, Farrag              MMY. The            potential protective role of alpha-lipoic acid against acetaminophen-induced hepatic and            renal damage. Toxicology. 2008;            243: 261\u2013270.","DOI":"10.1016\/j.tox.2007.10.010"},{"key":"29","unstructured":"31. Conover              WJ. Practical Nonparametric          Statistics. 3rd ed. New York: John Wiley &amp; Sons; 1999. p.          272\u2013288."},{"key":"30","doi-asserted-by":"crossref","unstructured":"32. Imlay              JA. Pathways of            oxidative damage. Annu Rev Microbiol.          2003; 57: 395\u2013418.","DOI":"10.1146\/annurev.micro.57.030502.090938"},{"key":"31","doi-asserted-by":"crossref","unstructured":"33. Dizdaroglu              M. Oxidatively            induced DNA damage and its repair in cancer. Mutat Res Rev Mutat            Res. 2015; 763:            212\u2013245.","DOI":"10.1016\/j.mrrev.2014.11.002"},{"key":"32","doi-asserted-by":"crossref","unstructured":"34. Wilkes              JM, Clark              LE, Herrera              JL.            Acetaminophen overdose in pregnancy. South Med            J. 2005; 98:            1118\u20131122.","DOI":"10.1097\/01.smj.0000184792.15407.51"},{"key":"33","doi-asserted-by":"crossref","unstructured":"35. Karaali              HF, Fahmi              RR, Borjac              JM. Effect of            Ocimum basilicum leaves extract on acetaminophen-induced nephrotoxicity in BALB\/c            mice. J Complement Integr Med. 2018;            16: 1\u201315.","DOI":"10.1515\/jcim-2018-0111"},{"key":"34","doi-asserted-by":"crossref","unstructured":"36. Akakpo              JY,                Ramachandran              A, Kandel              SE, Ni              HM, Kumer              SC, Rumack              BH, et            al. 4-Methylpyrazole protects against acetaminophen            hepatotoxicity in mice and in primary human hepatocytes. Hum Exp            Toxicol. 2018; 37:            1310\u20131322.","DOI":"10.1177\/0960327118774902"},{"key":"35","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1016\/S0899-9007(02)00916-4","volume":"18","year":"2002","unstructured":"37. Fang              YZ, Yang              S, Wu              G. Free            radicals, antioxidants, and nutrition. Nutrition.            2002; 18: 872\u2013879.","journal-title":"Nutrition","ISSN":"https:\/\/id.crossref.org\/issn\/0899-9007","issn-type":"print"},{"key":"36","doi-asserted-by":"crossref","unstructured":"38. Valko              M, Izakovic              M, Mazur              M, Rhodes              CJ, Telser              J. Role of            oxygen radicals in DNA damage and cancer incidence. Mol Cell            Biochem. 2004; 266:            37\u201356.","DOI":"10.1023\/B:MCBI.0000049134.69131.89"},{"key":"37","doi-asserted-by":"crossref","unstructured":"39. Kettle              AJ,                Winterbourn              CC.            Myeloperoxidase: a key regulator of neutrophil oxidant            production. Redox Rep. 1997;            3: 3\u201315.","DOI":"10.1080\/13510002.1997.11747085"},{"key":"38","doi-asserted-by":"crossref","unstructured":"40. Murad              HAS, Habib              H, Kamel              Y, Alsayed              S, Shakweer              M, Elshal              M. Thearubigins            protect against acetaminophen-induced hepatic and renal injury in mice: biochemical,            histopathological, immunohistochemical, and flow cytometry study.            Drug Chem Toxicol. 2016; 39:            190\u2013198.","DOI":"10.3109\/01480545.2015.1070170"},{"key":"39","doi-asserted-by":"crossref","unstructured":"41. Abdeen              A, Abdelkader              A, Abdo              M, Wareth              G, Aboubakr              M, Aleya              L, et            al. Protective effect of cinnamon against            acetaminophen-mediated cellular damage and apoptosis in renal tissue.            Environ Sci Pollut Res Int. 2019; 26:            240\u2013249.","DOI":"10.1007\/s11356-018-3553-2"},{"key":"40","doi-asserted-by":"crossref","unstructured":"42. Ozatik              FY, Teksen              Y, Kadioglu              E, Ozatik              O, Bayat              Z. Effects of            hydrogen sulfide on acetaminophen-induced acute renal toxicity in rats.            Int Urol Nephrol. 2019; 51:            745\u2013754.","DOI":"10.1007\/s11255-018-2053-0"},{"key":"41","doi-asserted-by":"crossref","unstructured":"43. Samuni              Y, Goldstein              S, Dean              OM, Berk              M. The            chemistry and biological activities of N-acetylcysteine. Biochim            Biophys Acta. 2013; 1830:            4117\u20134129.","DOI":"10.1016\/j.bbagen.2013.04.016"},{"key":"42","doi-asserted-by":"crossref","unstructured":"44. Talaulikar              V,                Arulkumaran              S. Folic acid            in pregnancy. Obstetrics, Gynaecol Reprod Med.            2013; 23: 286\u2013288.","DOI":"10.1016\/j.ogrm.2013.06.007"}],"container-title":["Experimental Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/expanim\/70\/1\/70_20-0075\/_pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,8]],"date-time":"2021-02-08T21:21:11Z","timestamp":1612819271000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/expanim\/70\/1\/70_20-0075\/_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021]]},"references-count":42,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021]]}},"URL":"https:\/\/doi.org\/10.1538\/expanim.20-0075","relation":{},"ISSN":["1341-1357","1881-7122"],"issn-type":[{"value":"1341-1357","type":"print"},{"value":"1881-7122","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021]]}}}