The Korea Journal of Herbology (대한본초학회지)

The Korea Association of Herbology (대한본초학회)
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Protective effect of Citri Unshius Pericarpium against cadmium-induced liver damage in mice

카드뮴으로 인한 마우스 간 손상에 대한 진피의 보호효과

  • Noh, Gyu Pyo (College of Korean Medicine, Daegu Haany University) ;
  • Lee, Jong Rok (Department of Pharmaceutical Engineering, Daegu Haany University) ;
  • Kim, Jae Kwang (Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine (KIOM)) ;
  • Park, Sang Mi (College of Korean Medicine, Daegu Haany University) ;
  • Park, Sook Jahr (Department of Pharmaceutical Engineering, Daegu Haany University) ;
  • Kim, Sang Chan (College of Korean Medicine, Daegu Haany University)
  • 노규표 (대구한의대학교 한의과대학) ;
  • 이종록 (대구한의대학교 제약공학과) ;
  • 김재광 (한국한의학연구원 한의기술응용센터) ;
  • 박상미 (대구한의대학교 한의과대학) ;
  • 박숙자 (대구한의대학교 제약공학과) ;
  • 김상찬 (대구한의대학교 한의과대학)
  • Received : 2020.11.12
  • Accepted : 2021.01.25
  • Published : 2021.01.30
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Abstract

Objective : Citri Unshius Pericarpium (Citrus unshiu peel) has been used in Korean medicine to treat indigestion, vomiting, coughing and phlegm. This study investigated the hepatoprotective effect of ethanol extract of Citrus unshiu peel (CEE) in cadmium (CdCl2)-treated mouse model. Methods : CEE was dissolved in water and administered orally to mice once a day for 7 consecutive days. The mice were then exposed to a single intraperitoneal (i.p.) injection of cadmium (4 mg/kg body weight) to induce acute hepatotoxicity. At the end of the experiment, blood and liver tissue samples were collected, analyzed for alanine aminotransferase (ALT), aspartate aminotransferase (AST), and histopathological evaluation. Liver damage was assessed as the percentage of degenerative areas of the hepatic parenchyma, the number of degenerative hepatocytes, and the number of infiltrated inflammatory cells. Results : In cadmium-treated rats, pretreatment with CEE significantly reduced the serum ALT and AST levels associated with liver damage. Histopathologically, CEE prevented degenerative changes on the hepatic tissues including confluent necrosis, congestions and infiltration of inflammatory cells. CEE also reduced the elevation of oxidative stress markers (nitrotyrosine and 4-hydroxynonenal) and apoptosis markers (cleaved caspase-3 and cleaved PARP) positive cells. PARP protein expression in liver tissue was also restored by CEE. Conclusion : This study showed that CEE exerted antioxidant and anti-apoptotic effects against cadmium-induced liver injury. Thus, it can be concluded that CEE can be used to prevent liver damage caused by cadmium.

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References

  1. Satarug S, Moore MR. Adverse health effects of chronic exposure to low-level cadmium in foodstuffs and cigarette smoke. Environ Health Perspect. 2004;112(10):1099-103. https://doi.org/10.1289/ehp.6751
  2. Jarup L, Åkesson A. Current status of cadmium as an environmental health problem. Toxicol Appl Pharmacol. 2009;238:201-8. https://doi.org/10.1016/j.taap.2009.04.020
  3. Menke A, Munter P, Silbergeld EK, Platz EA, Guallar E. Cadmium levels in urine and mortality among U.S. adults. Environ Health Perspect. 2009;117(2):190-6. https://doi.org/10.1289/ehp.11236
  4. Oriental Pharmacology Committee. Oriental Pharmacology. Seoul : Shinil. 2006 : 613-6.
  5. Jung JK, Son KH, Kim YS, Park YK. Effect of Citri Pericarpium ethanol extract on collagen-induced arthritis in mice. Kor J Herbology. 2011;26(3):1-6. https://doi.org/10.6116/KJH.2011.26.3.001
  6. Tsai YF, Chen YR, Chen JP, Tang Y, Yang KC. Effect of hesperidin on anti-inflammation and cellular antioxidant capacity in hydrogen peroxide-stimulated human articular chondrocytes. Process Biochem. 2019;85:175-84. https://doi.org/10.1016/j.procbio.2019.07.014
  7. Shi Q, Liu Z, Yang Y, Geng P, Zhu YY, Zhang Q, Bai F, Bai G. Identification of anti-asthmatic compounds in Pericarpium citri reticulatae and evaluation of their synergistic effects. Acta Pharmacol Sin. 2009;30: 567-75. https://doi.org/10.1038/aps.2009.36
  8. Yang G, Lee J, Jung ED, Ham I, Choi HY. Lipid lowering activity of Citri unshii pericarpium in hyperlipemic rats. Immunopharmacol Immunotoxicol. 2008;30:783-91. https://doi.org/10.1080/08923970802279167
  9. Shin YW. Changes in the anti allergic effect of Citrus unshii Pericarpium according to storage period. Kor J Herbology. 2012;27(5):37-44. https://doi.org/10.6116/kjh.2012.27.5.37
  10. Oh YL. Effect of antioxidant of Citri Reticulatae Pericarpium on cytotoxicity of oxygen free radicals in cultured NIH3T3 fibroblast. Kor J Herbology. 2006;21(4):143-8.
  11. Haouem S, Hmad N, Najjar MF, Hani AE, Sakly R. Accumulation of cadmium and its effects on liver and kidney functions in rats given diet containing cadmium-polluted radish bulb. Exp Toxicol Pathol. 2007;59:77-80. https://doi.org/10.1016/j.etp.2007.03.006
  12. Park SJ, Lee JR, Jo MJ, Park SM, Ku SK, Kim SC. Protective effects of Korean red ginseng extract on cadmium-induced hepatic toxicity in rats. J Ginseng Res. 2013;37:37-44. https://doi.org/10.5142/jgr.2013.37.37
  13. Rogalska J, Pilat-Marcinkiewicz B, Brzoska MM. Protective effect of zinc against cadmium hepatotoxicity depends on this bioelement intake and level of cadmium exposure: a study in a rat model. Chem Biol Interact. 2011;193:191-203. https://doi.org/10.1016/j.cbi.2011.05.008
  14. Li Y, Lim SC. Cadmium-induced apoptosis of hepatocytes is not associated with death receptor-related caspase-dependent pathways in the rat. Environ Toxicol Pharmacol. 2007;24:231-8. https://doi.org/10.1016/j.etap.2007.05.010
  15. Oyinloye BE, Adenowo AF, Osunsanmi FO, Ogunyinka BI, Nwozo SO, Kappo AP. Aqueous extract of Monodora myristica ameliorates cadmium-induced hepatotoxicity in male rats. Springerplus. 2016;5:641. https://doi.org/10.1186/s40064-016-2228-z
  16. Ramamurthy CH, Subastri A, Suyavaran A, Subbaiah KC, Valluru L, Thirunavukkarasu C. Solanum torvum Swartz. fruit attenuates cadmium-induced liver and kidney damage through modulation of oxidative stress and glycosylation. Environ Sci Pollut Res Int. 2016;23:7919-29. https://doi.org/10.1007/s11356-016-6044-3
  17. Luo T, Yuan Y, Yu Q, Liu G, Long M, Zhang K, Bian J, Gu J, Zou H, Wang Y, Zhu J, Liu X, Liu Z. PARP-1 overexpression contributes to Cadmium-induced death in rat proximal tubular cells via parthanatos and the MAPK signalling pathway. Sci Rep. 2017;7:4331. https://doi.org/10.1038/s41598-017-04555-2
  18. Aja PM, Izekwe FI, Famurewa AC, Ekpono EU, Nwite FE, Igwenyi IO, Awoke JN, Ani OG, Aloke C, Obasi NA, Udeh KU, Ale BA. Hesperidin protects against cadmium-induced pancreatitis by modulating insulin secretion, redox imbalance and iNOS/NF-κB signaling in rats. Life Sci . 2020;259:118268. https://doi.org/10.1016/j.lfs.2020.118268
  19. Khan MHA, Parvez S. Hesperidin ameliorates heavy metal induced toxicity mediated by oxidative stress in brain of Wistar rats. J Trace Elem Med Biol. 2015;31:53-60. https://doi.org/10.1016/j.jtemb.2015.03.002
  20. Leelavinothan P, Kalist S. Hesperetin protects against oxidative stress related hepatic dysfunction by cadmium in rats. Exp Toxicol Pathol. 2012;64(5): 513-20. https://doi.org/10.1016/j.etp.2010.11.007
  21. Lasfer M, Vadrot N, Aoudjehane L, Conti F, Bringuier AF, Feldmann G, Reyl-Desmars F. Cadmium induces mitochondria-dependent apoptosis of normal human hepatocytes. Cell Biol Toxicol. 2008;24(1):55-62. https://doi.org/10.1007/s10565-007-9015-0
  22. Toppo R, Roy BK, Gora RH, Baxla SL, Kumar P. Hepatoprotective activity of Moringa oleifera against cadmium toxicity in rats. Vet World. 2015;8:537-40. https://doi.org/10.14202/vetworld.2015.537-540
  23. Pacher P, Beckman JS, Liaudet L. Nitric oxide and peroxynitrite in health and disease. Physiol Rev. 2007;87:315-424. https://doi.org/10.1152/physrev.00029.2006
  24. Jin SY, Kang SS, Lee DW, Yim SJ, Yun YH, Lee BI. Expression of matrix metalloproteinase (MMP)-1, MMP-3 nitrotyrosine and apoptosis in articular cartilage of human osteoarthritis. Korean J Pathol. 2001;35(4):319-29.
  25. Bong JG, Park YY. Antioxidant effect of hederagenin 3-O-b-D-glucopyranosyl ( 1 → 3 )-a-L-rhamnopyranosyl (1→2)-a-L-arabinopyranoside(HDL) isolated from root bark of ulmus davidiana. J Life Sci. 2010;20(2):281-91. https://doi.org/10.5352/JLS.2010.20.2.281
  26. Ham MJ, Kim YS. Effects of Polygalae Radix Preparata Cum Glycyrrhizae Radix on 4-HNE-induced apoptosis in PC-12 cell. Kor J Herbology. 2016;31(1):77-82. https://doi.org/10.6116/kjh.2016.31.1.77.