Protective Effect of Joo-Juk on Acetaminophen-induced Liver Damage in Mouse Model

Acetaminophen 유도 간 손상에 대한 주적(酒敵)의 보호 효과

  • Kim, Sung-Zoo (Department of Physiology, Center for Healthcare Technology Development, Chonbuk National University Medical School) ;
  • Kang, Hyung-Sub (Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, Chonbuk National University) ;
  • Shin, Jae-Suk (Imsil Herbal Medicine Association) ;
  • Xie, Guang-Hua (Department of General Surgery, Affiliated Hospital of Yanbian University College of Medicine) ;
  • Huh, Jin (Department of Oriental medical prescription, Wonkwang University) ;
  • Jang, Seon-Il (School of Alternative Medicine & Health Science, College of Alternative Medicine, Jeonju University)
  • 김성주 (전북대학교 의학전문대학 헬스케어사업단 생리학교실) ;
  • 강형섭 (전북대학교 수의과대학 수의약리학교실) ;
  • 신재석 (임실생약영농조합) ;
  • 설광화 (중국 연변대학교 의과대학 일반외과) ;
  • 허진 (원광대학교 한의과대학 방제학교실) ;
  • 장선일 (전주대학교 대체의학대학 대체건강관리학부)
  • Published : 2009.12.30

Abstract

Acetaminophen (AP) is widely used as an over-the-counter analgesic and antipyretic drug. AP-induced hepatotoxicity is a common consequence of AP overdose and may lead to acute liver failure. In this study, we investigated the liver damage in mice using single dose (300 mg/kg) of AP and the possible protective effects of administration (50-200 mg/kg body weight) of Joo-Juk on acetaminophen-induced liver damage in mice. The alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activities were determined in the plasma of mice. The effect of Joo-Juk on lipid peroxidation product thiobarbituric reacting substances (TBARS) and some antioxidant enzymes superoxide dismutase (SOD), catalase, d-aminolevulinate dehydratase ($\sigma$-ALA-D) activities, and gluthathione peroxidase (GPx), were also evaluated in the mouse liver homogenate. AP caused liver damage as evident by statistically significant increased in plasma activities of AST and ALT. There were statistically significant losses in the activities of SOD, catalase, $\sigma$-ALA-D, and GPx and an increase in TBARS in the liver of AP-treated group compared with the control group. However, Joo-Juk was able to counteract these effects. These results suggest that Joo-juk can act as hepato-protectant against AP toxicity and is a good candidate for further evaluation as an effective chemotherapeutic agent.

Keywords

References

  1. Ray SD, Mumaw VR, Raje RR, Fariss MW. Protection of acetaminophen-induced hepatocellular apoptosis and necrosis by cholesteryl hemisuccinole pretreatment. J Pharmacol Exp Ther. 1996;279 :1470-83.
  2. Webster PA, Roberts DW, Benson RW, Kearns GL. Acetaminophen toxicity in children:diagnostic confirmation using a specific antigenic biomarker. J Clin Pharmacol. 1996;36:397-402 https://doi.org/10.1002/j.1552-4604.1996.tb05025.x
  3. Albano E, Rundgren M, Harvison PJ, Nelson SD, Moldeus P. Mechanisms of N-acetyl-p-benzoquinone -imine cytotoxicity. Mol Pharmacology. 1985;28: 306-11.
  4. Kyle ME, Miccadei S, Nakae D, Farber JL. Superoxide dismutase and catalase protect cultured hepatocytes from the cytotoxicity of acetaminophen. Biochem Biophys Res Commun. 1987;149:889-94. https://doi.org/10.1016/0006-291X(87)90491-8
  5. Mahadevan SB, McKiernan PJ, Davies P, Kelly DA. Paracetamol induced hepatotoxicity. Arch Dis Child. 2006 Jul;91(7):598-603.
  6. Prescott LF. Paracetamol, alcohol and the liver. Br J Clin Pharmacol. 2000;49(4):291-301.
  7. Prescott LF. Paracetamol:past, present, and future. Am J Ther. 2000;7(2):143-7. https://doi.org/10.1097/00045391-200007020-00011
  8. Yook CS. Colored Medicinal Plants of Korea. Seoul:Academy Book Publishing Company. 1993 :88-91.
  9. Namba T. The Encyclopedia of Wakan-Yaku (Traditional Sino-Japanese Medicines) with Color Pictures, Vol.II. Osaka:Hoikusha Publishing Company. 1993:92-5.
  10. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193:265
  11. Ohkawa H, Ohishi H, Yagi K. Assay for lipid peroxide in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95:351-8. https://doi.org/10.1016/0003-2697(79)90738-3
  12. Sassa S. Delta-aminolevulinic acid dehydratase assay. Enzyme. 1982;28:133-4 https://doi.org/10.1159/000459097
  13. Misra HP, Fridovich I. The role of superoxide anion in the autoxidation of epinephrine and simple assay for superoxide dismutase. J Biol Chem.1972;247:3170-5.
  14. Aebi H. Catalase. In:Bergmeyer HU, editor. Methods of enzymatic analysis. Weinheim: Verlag Chemie. 197:673-7.
  15. Paglia DE, Valentine WN. Studies on the guantitative characterisation of erythrocyte glutathione peroxidase. J Lab Clin Med. 1967 ;70:158-67
  16. Janbaz KH, Saeed SA, Gilani TA. Protective effect of rutin on paracetamol- and CCl4- induced hepatotoxicity in rodents. Fitoterapia. 2002;73:557-63. https://doi.org/10.1016/S0367-326X(02)00217-4
  17. Ali BH, Bashir AK, Rasheed RA. Effect of the traditional medicinal plants Rhazya stricta, Balanitis aegyptiaca and Haplophylum tuberculatum on paracetamol-induced hepatotoxicity in mice. Phytother Res.2001;15:598-603. https://doi.org/10.1002/ptr.818
  18. .Kozer E, Evans S, Barr J, Greenberg R, Soriano I, Bulkowstein M, et al. Glutathione, glutathione -dependent enzymes and antioxidant status in erythrocytes from children treated with high-dose paracetamol. Br J Clin Pharmacol. 2003;55:234-40. https://doi.org/10.1046/j.1365-2125.2003.01723.x
  19. Hinson JA, Pohl LR, Monks TJ, Gillele JR, Guengerich FP. 3-Hydroxyacetaminophen. A microsomal metabolites of acetaminophen. Evidence against an epoxide as the reactive metabolite of acetaminophen. Drug Metab Dispos. 1980;8:289-94.
  20. Olaleye MT, Rocha BT. Acetaminophen-induced liver damage in mice:effects of some medicinal plants on the oxidative defense system. Exp Toxicol Pathol. 2008;59(5):319-27 https://doi.org/10.1016/j.etp.2007.10.003
  21. Younes M, Siegers CP. The role of Iron in the paracetamol and CCl4-induced lipid peroxidation and hepatotoxicity. Chem Biol Interact. 1985;55:327-34 https://doi.org/10.1016/S0009-2797(85)80139-3
  22. Katyare SS, Satav JG. Altered kinetic properties of liver mitochondrial membrane–bondenzymes activities following paracetamol hepatotoxicity in rat. J Biosci. 1991;16:71-9. https://doi.org/10.1007/BF02720052
  23. Katikova O. Effect of mexidol on the homeostatis and lipid peroxidation in paracetamol poisoning. Eksp Klim Farmakol. 2002;65:53-6.
  24. Jang SI, Kim HJ, Hwang KM, Jekal SJ, Pae HO, Choi BM, Yun YG, Kwon TO, Chung HT, Kim YC. Hepatoprotective effect of baicalin, a major flavone from Scutellaria radix, on acetaminophen-induced liver injury in mice. Immunopharmacol Immunotoxicol. 2003;25:585-94. https://doi.org/10.1081/IPH-120026443
  25. Kim ST, Kim JD, Ahn SH, Ahn GS, Lee YI, Jeong YS. Hepatoprotective and antioxidant effects of Alnus japonica extracts on acetaminophen-induced hepatotoxicity in rats. Phytother Res. 2004;18(12):971-5. https://doi.org/10.1002/ptr.1540
  26. Park JC, Hur JM, Park JG, Kim SC, Park JR, Choi SH, Choi JW. Effects of methanol extract of Cirsium japonicum var. ussuriense and its principle, hispidulin-7-O-neohesperidoside on hepatic alcohol-metabolizing enzymes and lipid peroxidation in ethanol-treated rats. Phytother Res.2004;18(1):19-24. https://doi.org/10.1002/ptr.1299
  27. Bae HS, Kim YS, Cho KH, Lee KS, Kim JJ, Lee HU, Kim DH. Hepatoprotective activity of reduohanxiao-tang (yuldahanso-tang) is related to the inhibition of beta-glucuronidase. Am J Chin Med. 2003;31(1):111-7. https://doi.org/10.1142/S0192415X03000722
  28. Arnaiz SL, Llesuy S, Curtrın JC, Boveris A. Oxidative stress by acute acetaminophen administration in mouse liver. Free Radical Biol Med. 1995;19:303 https://doi.org/10.1016/0891-5849(95)00023-Q
  29. Soares JCM, Folmer V, Rocha JBT. Influence of dietary selenium supplementation and exercise on thiol-containing enzymesinmice. Nutrition. 2003;19:627 https://doi.org/10.1016/S0899-9007(03)00065-0
  30. Folmer V, Soares JC, Rocha JBT. Oxidative stress in mice is dependent on the free glucose content of the diet. Int J Biochem Cell Biol. 2002;34:1279. https://doi.org/10.1016/S1357-2725(02)00065-1
  31. Bechara EJH. Oxidative stress in acute intermittent porphyria and lead poisoning may be triggered by 5-aminolevulinicacid. Brazil J Med Biol Res.1996;29:841
  32. Bessems JM, Vermeulen NPE. Paracetamol (Acetaminophen)-induced toxicity: molecular and biochemical mechanism. Analogues Protective Approaches 2001.
  33. Rajesh B, Parames CS. Theprotein fraction of Phyllanthus niruri plays a protective role against acetaminophen induced hepatic disorder via its antioxidant properties. Phytother Res. 2006;120:595-601.
  34. Adamson GM, Harman AW. A rolefor the glutathione peroxidase/reductase enzymesy stem in the protection from paracetamol toxicity in isolated mouse hepatocytes. Biochem Pharmacol 1989;38:3323-30. https://doi.org/10.1016/0006-2952(89)90630-8