Antioxidant effect of Abelmoschus Esculentus against acetaminophen-induced nephrotoxicity: an experimental study

Mervan Bekdas, Arzu Meyri Yoldas, Aysegul Danıs, Selma Erdogan Duzcu, Murat Alisik, Ayhan Cetinkaya, Huseyin Kocabey, Idris Turel, Mustafa Dilek, Gokce Kaya Dincel

Abstract


Acetaminophen(APAP) intoxication is an important cause of nephrotoxicity and hepatotoxicity. N-acetylcysteine(NAC) is used in the treatment, but it has some serious side effects. Abelmoschus esculentus(AE) has various benefits as well as antioxidant effects. This study aims to investigate the effect of AE in APAP-induced acute nephrotoxicity. Forty male Wistar rats were divided into five equal groups: Control, AE, APAP, APAP+AE, and APAP+AE+NAC. Significant changes were observed in serum levels of malondialdehyde (MDA), superoxide dismutase (SOD), Neutrophil Gelatinase-Associated Lipocalin(NGAL) and Kidney Injury Molecule-1(KIM-1) after induction with APAP. NGAL and KIM-1 in the AE group remained low compared to those receiving APAP (p=0.022 and p<0.001, respectively). When the APAP group was compared with the AE and AE+NAC groups, it was found that even the administration of AE alone significantly decreased NGAL and KIM-1(p=0.036 vs.p=0.029 and p<0.001 vs. p<0.001, respectively), these results were attributed to the effects of AE on reducing MDA and increasing SOD. Histopathological studies also confirmed these results. These results demonstrated that AE had protective and therapeutic effects on APAP-induced nephrotoxicity. This benefit of AE is due to its antioxidant effect. In addition, AE may also increase the regenerative capacity of the kidney, which APAP reduces.


Keywords


Abelmoschus Esculentus; Acetaminophen; MDA; Nephrotoxicity; SOD

Full Text:

PDF

References


Ogilvie JD, Rieder MJ, Lim R. 2012. Acetaminophen overdose in children: Figure 1: Canadian Medical Association Journal. 184(13):1492–6. Available from: http://www.cmaj.ca/lookup/doi/10.1503/cmaj.111338

Lancaster EM, Hiatt JR, Zarrinpar A. 2015. Acetaminophen hepatotoxicity: an updated review. Archives of Toxicology. 89(2):193–9. Available from: http://link.springer.com/10.1007/s00204-014-1432-2

Murad HAS, Habib H, Kamel Y, Alsayed S, Shakweer M, Elshal M. 2016. Thearubigins protect against acetaminophen-induced hepatic and renal injury in mice: biochemical, histopathological, immunohistochemical, and flow cytometry study. Drug and Chemical Toxicology. 39(2):190–8. Available from: http://www.tandfonline.com/doi/full/10.3109/01480545.2015.1070170

Bessems JGM, Vermeulen NPE. 2001.Paracetamol (Acetaminophen)-Induced Toxicity: Molecular and Biochemical Mechanisms, Analogues and Protective Approaches. Critical Reviews in Toxicology. 31(1):55–138. Available from: http://www.tandfonline.com/doi/full/10.1080/20014091111677

Jones AF, Vale JA. 1993. Paracetamol poisoning and the kidney. Journal of Clinical Pharmacy and Therapeutics. 18(1):5–8. Available from: http://doi.wiley.com/10.1111/j.1365-2710.1993.tb00560.x

Mahadevan SBK, McKiernan PJ, Davies P, Kelly DA. 2005. Paracetamol induced hepatotoxicity. Archives of Disease in Childhood. 91(7):598–603. Available from: https://adc.bmj.com/lookup/doi/10.1136/adc.2005.076836

Saccomano SJ. 2019. Acute acetaminophen toxicity in adults. The Nurse Practitioner. 44(11):42–7. Available from: https://journals.lww.com/10.1097/01.NPR.0000586020.15798.c6

Kostic M. 2016. Poisoning. In: Kliegman R, Stanton B, St. Geme J, Schor N, editors. Nelson Textbook of Pediatrics. Philadelphia: Elsevier. p. 447–67.

Hanly LN, Chen N, Aleksa K, Cutler M, Bajcetic M, Palassery R, et al. 2012. N-acetylcysteine as a Novel Prophylactic Treatment for Ifosfamide-Induced Nephrotoxicity in Children: Translational Pharmacokinetics. The Journal of Clinical Pharmacology. 52(1):55–64. Available from: http://doi.wiley.com/10.1177/0091270010391790

Bateman DN, Dear JW, Thanacoody HKR, Thomas SHL, Eddleston M, Sandilands EA, et al. 2014. Reduction of adverse effects from intravenous acetylcysteine treatment for paracetamol poisoning: a randomized controlled trial. The Lancet. 383(9918):697–704. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0140673613620620

Whyte IM, Francis B, Dawson AH. 2007. Safety and efficacy of intravenous N‐acetylcysteine for acetaminophen overdose: analysis of the Hunter Area Toxicology Service (HATS) database. Current Medical Research and Opinion. 23(10):2359–68. Available from: http://www.tandfonline.com/doi/full/10.1185/030079907X219715

Sanaei-Zadeh H, Taghaddosinejad F, Jalali N, Kariman H. 2003. Adverse Effects of Intravenous N-Acetylcysteine. Clinical Drug Investigation. 23(2):129–33. Available from: http://link.springer.com/10.2165/00044011-200323020-00006

Shui G, Peng LL. 2004. An improved method for the analysis of major antioxidants of Hibiscus esculentus Linn. Journal of Chromatography A. 1048(1):17–24. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0021967304011872

Shah B, Seth A, Maheshwari K, Desai R. 2010. Screening of abelmoschus esculentus fruits for its analgesic activity. Pharmacology Online. 2:17–21.

Kordali S, Cakir A, Akcin TA, Mete E, Akcin A, Aydin T, et al. 2009. Antifungal and herbicidal properties of essential oils and n-hexane extracts of Achillea gypsicola Hub-Mor. and Achillea biebersteinii Afan. (Asteraceae). Industrial Crops and Products. 29(2–3):562–70. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0926669008002070

Xia F, Zhong Y, Li M, Chang Q, Liao Y, Liu X, et al. 2015. Antioxidant and Anti-Fatigue Constituents of Okra. Nutrients. 7(10):8846–58. Available from: http://www.mdpi.com/2072-6643/7/10/5435

Kouritas VK, Magkouta S, Zisis C, Psallidas I, Gourgoulianis KI, Kalomenidis I. 2015. Paracetamol and ibuprofen block hydrothorax absorption in mice†. European Journal of Cardio-Thoracic Surgery. 47(3):426–30. Available from: https://academic.oup.com/ejcts/article-lookup/doi/10.1093/ejcts/ezu211

Mahmoud YI, Mahmoud AA. 2016. Role of nicotinamide (vitamin B3) in acetaminophen-induced changes in rat liver. Experimental and Toxicologic Pathology. 68(6):345–54. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0940299316300537

Masubuchi Y, Nakayama J, Watanabe Y. 2011. Sex difference in susceptibility to acetaminophen hepatotoxicity is reversed by buthionine sulfoximine. Toxicology. 287(1–3):54–60. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0300483X11002125

Eakins R, Walsh J, Randle L, Jenkins RE, Schuppe-Koistinen I, Rowe C, et al. 2015. Adaptation to acetaminophen exposure elicits major changes in expression and distribution of the hepatic proteome. Scientific Reports. 5(1):16423. Available from: http://www.nature.com/articles/srep16423

Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, et al. 2020. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Internal Medicine. 180(7):934. Available from: https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2763184

Basol N, Savas AY, Meral A, Erbas O. 2018. The valuable effects of potent antioxidant curcumin in cisplatin-induced liver and kidney injury. Cumhuriyet Medical Journal. 721–30. Available from: http://dergipark.gov.tr/doi/10.7197/223.vi.407571

Battal D, Hilal A, Daglioglu K, Unal I, Gulmen M. 2013. Evaluation of paracetamol distribution and stability in case of acute intoxication in rats. Human & Experimental Toxicology. 32(1):82–9. Available from: http://journals.sagepub.com/doi/10.1177/0960327112456314

Mazer M, Perrone J. 2008. Acetaminophen-induced nephrotoxicity: Pathophysiology, clinical manifestations, and management. Journal of Medical Toxicology. 4(1):2–6. Available from: http://link.springer.com/10.1007/BF03160941

Mansuroğlu B, Derman S, Yaba A, Kızılbey K. 2015. Protective effect of chemically modified SOD on lipid peroxidation and antioxidant status in diabetic rats. International Journal of Biological Macromolecules. 72:79–87. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0141813014005145

Herrera J, Rodriguez-Iturbe B. 1998. Stimulation of tubular secretion of creatinine in health and in conditions associated with reduced nephron mass. Evidence for a tubular functional reserve. Nephrology Dialysis Transplantation. 13(3):623–9. Available from: https://academic.oup.com/ndt/article-lookup/doi/10.1093/ndt/13.3.623

Haase M, Kellum JA, Ronco C. 2012. Subclinical AKI—an emerging syndrome with important consequences. Nature Reviews Nephrology. 8(12):735–9. Available from: http://www.nature.com/articles/nrneph.2012.197

Ozatik FY, Teksen Y, Kadioglu E, Ozatik O, Bayat Z. 2019. Effects of hydrogen sulfide on acetaminophen-induced acute renal toxicity in rats. International Urology and Nephrology. 51(4):745–54. Available from: http://link.springer.com/10.1007/s11255-018-2053-0

Devarajan P. 2008. NGAL in Acute Kidney Injury: From Serendipity to Utility. American Journal of Kidney Diseases. 52(3):395–9. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0272638608011116

Roudkenar MH, Halabian R, Bahmani P, Roushandeh AM, Kuwahara Y, Fukumoto M. 2011. Neutrophil gelatinase-associated lipocalin: A new antioxidant that exerts its cytoprotective effect independent on Heme Oxygenase-1. Free Radical Research. 45(7):810–9. Available from: http://www.tandfonline.com/doi/full/10.3109/10715762.2011.581279

Roudkenar MH, Halabian R, Ghasemipour Z, Roushandeh AM, Rouhbakhsh M, Nekogoftar M, et al. 2008. Neutrophil Gelatinase-associated Lipocalin Acts as a Protective Factor against H2O2 Toxicity. Archives of Medical Research. 39(6):560–6. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0188440908001392

Mori K, Nakao K. 2007. Neutrophil gelatinase-associated lipocalin as the real-time indicator of active kidney damage. Kidney International. 71(10):967–70. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0085253815522448

Mishra J. 2004. Amelioration of Ischemic Acute Renal Injury by Neutrophil Gelatinase-Associated Lipocalin. Journal of the American Society of Nephrology. 15(12):3073–82. Available from: http://www.jasn.org/cgi/doi/10.1097/01.ASN.0000145013.44578.45

Zhou Y, Vaidya VS, Brown RP, Zhang J, Rosenzweig BA, Thompson KL, et al. 2008. Comparison of Kidney Injury Molecule-1 and Other Nephrotoxicity Biomarkers in Urine and Kidney Following Acute Exposure to Gentamicin, Mercury, and Chromium. Toxicological Sciences. 101(1):159–70. Available from: https://academic.oup.com/toxsci/article/1658725/Comparison

Chiusolo A, Defazio R, Zanetti E, Mongillo M, Mori N, Cristofori P, et al. 2010. Kidney Injury Molecule-1 Expression in Rat Proximal Tubule after Treatment with Segment-Specific Nephrotoxicants. Toxicologic Pathology. 38(3):338–45. Available from: http://journals.sagepub.com/doi/10.1177/0192623310362244

Ismail OZ, Zhang X, Wei J, Haig A, Denker BM, Suri RS, et al. 2015. Kidney Injury Molecule-1 Protects against Gα12 Activation and Tissue Damage in Renal Ischemia-Reperfusion Injury. The American Journal of Pathology. 185(5):1207–15. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0002944015000784

Humphreys BD, Xu F, Sabbisetti V, Grgic I, Naini SM, Wang N, et al. 2013. Chronic epithelial kidney injury molecule-1 expression causes murine kidney fibrosis. Journal of Clinical Investigation. 123(9):4023–35. Available from: http://www.jci.org/articles/view/45361

Zuk A, Bonventre J V. 2016. Acute Kidney Injury. Annual Review of Medicine. 67(1):293–307. Available from: http://www.annualreviews.org/doi/10.1146/annurev-med-050214-013407

Zhou Y, Vaidya VS, Brown RP, Zhang J, Rosenzweig BA, Thompson KL, et al. 2008. Comparison of Kidney Injury Molecule-1 and Other Nephrotoxicity Biomarkers in Urine and Kidney Following Acute Exposure to Gentamicin, Mercury, and Chromium. Toxicological Sciences. 101(1):159–70.

Liao Z, Zhang J, Wang J, Yan T, Xu F, Wu B, et al. 2019. The anti-nephritic activity of a polysaccharide from okra (Abelmoschus esculentus (L.) Moench) via modulation of AMPK-Sirt1-PGC-1α signaling axis mediated anti-oxidative in type 2 diabetes model mice. International Journal of Biological Macromolecules. 140:568–76. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0141813019341388

Wahyuningsih SPA, Atika BND, Sajidah ES, Winarni D. 2020. Nephroprotective activity of okra pods extract ( Abelmoschus esculentus L.) in sodium nitrite-induced mice. Research Journal of Pharmacy and Technology. 13(8):3648. Available from: http://www.indianjournals.com/ijor.aspx?target=ijor:rjpt&volume=13&issue=8&article=018




DOI: https://doi.org/10.18196/jfaps.v3i1.15284

Refbacks

  • There are currently no refbacks.


Creative Commons License
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.

Journal of Fundamental and Applied Pharmaceutical Science are indexed by:

       

Office:

K.H. Sudja Building G3, 2nd Floor, Faculty of Medicine and Health Science, Universitas Muhammadiyah Yogyakarta,
Jalan Brawijaya (Lingkar Selatan), Tamantirto, Kasihan, Bantul, Daerah Istimewa Yogyakarta.
Whatsapp: +62 822-2155-6698
Email: jfaps@umy.university
Website: http://journal.umy.ac.id/index.php/jfap/index

Creative Commons License

Journal of Fundamental and Applied Pharmaceutical Science is licensed under a Creative Commons Attribution-ShareAlike 4.0 International (CC BY-SA 4.0) license.