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A Protective Role of Okadaic Acid in Liver Injury Induced by Amoxicillin

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This study was performed to investigate whether okadaic acid (200 ng/kg) produces a protective effect in experimental liver injury induced by intragastric administration of 1000, 2000, and 4000 mg/kg amoxicillin in Sprague-Dawley rats (n=50). The control group was given carboxymethylcellulose sodium solution. Liver injury was assessed by the relative organ weight index, serum ALT activity, and liver malondialdehyde content. Histopathological examination of the liver from rats treated with amoxicillin revealed cell swelling, congestion, apoptosis, and necrosis. The relative liver weight index, ALT activity, and liver malondialdehyde content in these animals were higher than in the control. Administration of okadaic acid reduced the degree of amoxicillin-induced damage to hepatocytes. Thus, okadaic acid can alleviate liver injury caused by amoxicillin.

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References

  1. Aggarwal A, Jaswal N, Jain R, Elsiesy H. Amoxicillin-clavulanate- induced Granulomatous Hepatitis: Case Report and Review of the Literature. J. Clin. Transl. Hepatol. 2019;7(3):280- 283. doi: https://doi.org/10.14218/JCTH.2019.00027

    Article  PubMed  PubMed Central  Google Scholar 

  2. Álvarez Otero J, González L, Enríquez Gómez H, de la Fuente Aguado J. Cholestatic hepatitis caused by amoxicillin-clavulanate of torpid evolution. Enferm. Infecc. Microbiol. Clin. 2016;34(2):139-140. doi: https://doi.org/10.1016/j.eimc.2015.06.004

    Article  PubMed  Google Scholar 

  3. Chalasani N, Fontana RJ, Bonkovsky HL, Watkins PB, Davern T, Serrano J, Yang H, Rochon J; Drug Induced Liver Injury Network (DILIN). Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology. 2008;135(6):1924-1934, 1934.e1-4. doi: https://doi.org/10.1053/j.gastro.2008.09.011

    Article  PubMed  Google Scholar 

  4. Chen L, Ma L, Bai Q, Zhu X, Zhang J, Wei Q, Li D, Gao C, Li J, Zhang Z, Liu C, He Z, Zeng X, Zhang A, Qu W, Zhuang Z, Chen W, Xiao Y. Heavy metal-induced metallothionein expression is regulated by specific protein phosphatase 2A complexes. J. Biol. Chem. 2014;289(32):22 413-22 426. doi: https://doi.org/10.1074/jbc.M114.548677

    Article  CAS  Google Scholar 

  5. deLemos AS, Ghabril M, Rockey DC, Gu J, Barnhart HX, Fontana RJ, Kleiner DE, Bonkovsky HL; Drug-Induced Liver Injury Network (DILIN). Amoxicillin-Clavulanate-Induced Liver Injury. Dig. Dis. Sci. 2016;61(8):2406-2416. doi: https://doi.org/10.1007/s10620-016-4121-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Dounay AB, Forsyth CJ. Okadaic acid: the archetypal serine/ threonine protein phosphatase inhibitor. Curr. Med. Chem. 2002;9(22):1939-1980. doi: https://doi.org/10.2174/0929867023368791

    Article  CAS  PubMed  Google Scholar 

  7. Ferrer P, Amelio J, Ballarín E, Sabaté M, Vidal X, Rottenkolber M, Schmiedl S, Laporte JR, Ibáñez L; PROTECT Work Package 2. Systematic Review and Meta-Analysis: Macrolides- and Amoxicillin/Clavulanate-induced Acute Liver Injury. Basic Clin. Pharmacol. Toxicol. 2016;119(1):3-9. doi: https://doi.org/10.1111/bcpt.12550

    Article  CAS  PubMed  Google Scholar 

  8. Fu LL, Zhao XY, Ji LD, Xu J. Okadaic acid (OA): Toxicity, detection and detoxification. Toxicon. 2019;160):1-7. doi: https://doi.org/10.1016/j.toxicon.2018.12.007

    Article  CAS  PubMed  Google Scholar 

  9. Herrero-Herrero JI, García-Aparicio J. Corticosteroid therapy in a case of severe cholestasic hepatitis associated with amoxicillin- clavulanate. J. Med. Toxicol. 2010;6(4):420-423. doi: https://doi.org/10.1007/s13181-010-0019-4

    Article  PubMed  PubMed Central  Google Scholar 

  10. Larrey D, Vial T, Micaleff A, Babany G, Morichau-Beauchant M, Michel H, Benhamou JP. Hepatitis associated with amoxycillin-clavulanic acid combination report of 15 cases. Gut. 1992;33(3):368-371. doi: https://doi.org/10.1136/gut.33.3.368

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Lee J, Ji SC, Kim B, Yi S, Shin KH, Cho JY, Lim KS, Lee SH, Yoon SH, Chung JY, Yu KS, Park HS, Kim SH, Jang IJ. Exploration of Biomarkers for Amoxicillin/Clavulanate-Induced Liver Injury: Multi-Omics Approaches. Clin. Transl. Sci. 2017;10(3):163-171. doi: https://doi.org/10.1111/cts.12425

    Article  CAS  PubMed  Google Scholar 

  12. Li C, Jin J. The pathogenesis and clinical features of liver injury caused by antimicrobial agents. Herald of Medicine. 2016;35(Suppl):76-78. doi: https://doi.org/10.3870/j.issn.1004-0781.2016.z1.035

    Article  Google Scholar 

  13. Lu N, Liu Y, Tang A, Chen L, Miao D, Yuan X. Hepatocytespecific ablation of PP2A catalytic subunit α attenuates liver fibrosis progression via TGF-β1/Smad signaling. Biomed. Res. Int. 2015;2015:794862. doi: https://doi.org/10.1155/2015/794862

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Mateos R, Lecumberri E, Ramos S, Goya L, Bravo L. Determination of malondialdehyde (MDA) by high-performance liquid chromatography in serum and liver as a biomarker for oxidative stress. Application to a rat model for hypercholesterolemia and evaluation of the effect of diets rich in phenolic antioxidants from fruits. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2005;827(1):76-82. doi: https://doi.org/10.1016/j.jchromb.2005.06.035

    Article  CAS  PubMed  Google Scholar 

  15. Zhu XN, Chen LP, Bai Q, Ma L, Li DC, Zhang JM, Gao C, Lei ZN, Zhang ZB, Xing XM, Liu CX, He ZN, Li J, Xiao YM, Zhang AH, Zeng XW, Chen W. PP2A-AMPKα-HSF1 axis regulates the metal-inducible expression of HSPs and ROS clearance. Cell Signal. 2014;26(4):825-832. doi: https://doi.org/10.1016/j.cellsig.2014.01.002

    Article  CAS  PubMed  Google Scholar 

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Correspondence to X. Zhu.

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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 172, No. 9, pp. 318-322, September, 2021

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Li, D., Shi, W., Lu, X. et al. A Protective Role of Okadaic Acid in Liver Injury Induced by Amoxicillin. Bull Exp Biol Med 172, 328–331 (2022). https://doi.org/10.1007/s10517-022-05386-6

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  • DOI: https://doi.org/10.1007/s10517-022-05386-6

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