A Study on the Protective Effect of Antioxidants on Damage Induced by Liver Ischemia/Repefusion in a Rat Model
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
The hepatic ischemic model has recently been widely used for the epidemiological study of ischemic reperfusion injury. This study was carried out to investigate the protective effect of vanillin, which is known to have antioxidant and anti-inflammatory effects, against hepatic and renal injury using an ischemia-reperfusion rat model, and we also investigated the mechanism related to vanillins’ protective effect. The test material was administered at a concentration of 100 mg/kg for 3 days, followed by ligation of the liver for 60 minutes to induce ischemia reperfusion. As control groups, there was a negative control, sham control and ischemia-reperfusion-only ischemia reperfusion control, and the controls groups were compared with the drug administration group. In the vanillin group, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were significantly inhibited compared with the AST and ALT activities of the ischemia-reperfusion group, and histopathological examination showed significant reduction of both inflammation and necrosis. The malondialdehyde (MDA) and superoxide dismutase (SOD) levels were significantly different from the ischemia-reperfusion group. In conclusion, vanillin showed a hepatocyte protective action by alleviating the cellular inflammation and cell necrosis caused by hepatic ischemia-reperfusion, and vanillin mitigated inflammatory changes in the kidney glomeruli and distal tubules. The protective effect is considered to be caused by vanillin’s antioxidant function. Further studies such as on cell death and possibly vanillin’s same effect on damaged tissue will be necessary for clinical applications such as organ transplantation.
Abstract
The hepatic ischemic model has recently been widely used for the epidemiological study of ischemic reperfusion injury. This study was carried out to investigate the protective effect of vanillin, which is known to have antioxidant and anti-inflammatory effects, against hepatic and renal injury using an ischemia-reperfusion rat model, and we also investigated the mechanism related to vanillins’ protective effect. The test material was administered at a concentration of 100 mg/kg for 3 days, followed by ligation of the liver for 60 minutes to induce ischemia reperfusion. As control groups, there was a negative control, sham control and ischemia-reperfusion-only ischemia reperfusion control, and the controls groups were compared with the drug administration group. In the vanillin group, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were significantly inhibited compared with the AST and ALT activities of the ischemia-reperfusion group, and histopathological examination showed significant reduction of both inflammation and necrosis. The malondialdehyde (MDA) and superoxide dismutase (SOD) levels were significantly different from the ischemia-reperfusion group. In conclusion, vanillin showed a hepatocyte protective action by alleviating the cellular inflammation and cell necrosis caused by hepatic ischemia-reperfusion, and vanillin mitigated inflammatory changes in the kidney glomeruli and distal tubules. The protective effect is considered to be caused by vanillin’s antioxidant function. Further studies such as on cell death and possibly vanillin’s same effect on damaged tissue will be necessary for clinical applications such as organ transplantation.
참고문헌 (41)
- Champion HR, "A clinicopathologic study of hepatic dysfunction following shock", Surg Gynecol Obstet, 142, pp.657~663 (1976)
- Kanufman RP, "Vasodilator prostaglandins prevent renal damage after ischemia", Ann Surg, 205, pp.195~198 (1987)
- Stephensen KR, "Perioperative blood transfusions are associated with decreased time to recurrence and decreased survival after resection of colorectal liver metastasis", Ann Surg, 208, pp.679~687 (1988)
- Matsumata T, "Decreased morbidity and mortality rates in surgical patients with hepatocellular carcinoma", Br J Surg, 77, pp.677~680 (1990)
- Taniguchi H, "Analysis of 210 elective hepatic resections", Hepatogastroenterology, 44, pp.1624~1631 (1997)
- Fujimoto J, "Adverse effect of perioperative blood transfusions on survivial after hepatic resection for epatocellular ciacinoma", Hepatogastroenterology, 44, pp.1390~1396 (1997)
- Demetrios V, "Deferoxamine attenuates lipid peroxidation, blocks Interleukin-6 production, ameliorates sepsis inflammatory response syndrome, and confers renoprotection after acute hepatic ischemia in pigs", Artif Organs, 36, pp.400~408 (2012)
- Lee HT, "Acute kidney injury after hepatic ischemia and reperfusion injury in mice", Lab Invest, 89, pp.196~208 (2009)
- Daemen MA, "Apoptosis and inflammation in renal reperfusion injury", Transplantation, 73, pp.1693~1700 (2002)
- Seifi B, "Pretreatment with pentoxifylline and N-acetylcysteine in liver ischemia reperfusion-induced renal injury", Ren Fail, 34, pp.610~615 (2012)
- Korthuis RJ, "Reactive oxygen metabolites, neutrophils, and the pathogenesis of ischemic-tissue", reperfusion, 1993, pp.16(4 Suppl 1), 19~26
- Tsung A, "The nuclear factor HMGB1 mediates hepatic injury after murine liver ischemiareperfusion", J Exp Me, 201, pp.1135~1143 (2005)
- Brand K, "Aerobic glycolysis by proliferating cells : protection against oxidative stress at the expense of energy yield", J Bioenerg Biomembr, 29, pp.355~364 (1997)
- Lirdprapamongkol K, "Vanillin suppresses in vitro invasion and in vivo metastasis of mouse breast cancer cells", Eur J Pharm Sci, 25, pp.57~65 (2005)
- Cheng WY, "Relationship between San-Huang-Xie-Xin-Tang and its herbal components on the gene expression profiles in HepG2 cells", Am J Chin Med, 36, pp.783~797 (2008)
- Liang JA, "Vanillin inhibits matrix metalloproteinase-9 expression through down-regulation of nuclear factor-B signaling pathway in human hepatocellular carcinoma cells", Mol Pharmacol, 75, pp.151~157 (2009)
- Durant. S, "Vanillins-a novel family of DNA-PK inhinitors", Nucleiic Acids Res, 31, pp.5501~5512 (2003)
- Fitzgerald DJ, "Mode of antimicrobial action of vanillin against Escherichia coli, Lactobacillus plantarum and Listeria innocua", J Appl Microbiol, 97, pp.104~113 (2004)
- Santosh Kumar SS, "Inhibition of peroxynitrite- mediated reactions by vanillin", J Agric Food Chem, 52, pp.139~145 (2004)
- Roumen RM, "Cytokine patterns in patients after major vascular surgery, hemorrhagic shock, and severe blunt trauma, Relation with subsequent adult respiratory distress syndrome and multiple organ failure", Ann Surg, 218, pp.769~776 (1993)
- Klebanoff SJ, "Stimulation of neutrophils by tumor necrosis factor", J Immunol, 136, pp.4220~4225 (1986)
- Gomez-Cambronero LG, "Role of cytokines and oxidative stress in the pathophysiology of acute pancreatitis : therapeutical implications", Current Drug Targets Inflamm Allergy, 1, pp.393~403 (2002)
- Zingarelli B, "Nuclear factor-kappa B as a therapeutic target in critical care medicine", Critical Care Medicine, 31(1 Suppl), pp.105~111 (2003)
- Sasaki H, "Activation of apoptosis during the reperfusion phase after rat liver ischemia", Transplant Proc, 28, pp.1908~1909 (1996)
- Nankivell BJ, "Chronic allograft nephropathy : current concepts and future directions", Transplantation, 81, pp.643~654 (2006)
- Wald R, "Acute renal failure after endovascular vs open repair of abdominal aortic aneurysm", J Vasc Surg, 43, pp.460~466 (2006)
- Matas AJ, "Acute renal failure following blunt civilian trauma", Ann Surg, 185, pp.301~306 (1977)
- Dame JB, "The distribution of receptors for the pro-inflammatory cytokines interleukin(IL)-6 and IL-8 in the developing human fetus", Early Hum Dev, 58, pp.25~39 (2000)
- Horii Y, "Involvement of IL-6 in measangial proliferative glomerulonephritis", J Immunol, 143, pp.3949~3955 (1989)
- Taniguchi Y, "Interleukin-6 localization and the prognosis of Ig A nephropathy", Nephron, 81, pp.94~98 (1999)
- Homis E, "Interleukin-6 stimulates tubular regeneration in rats with glycerol-induced acute renal failure", Nephron, 92, pp.192~199 (2002)
- Ruiz-Ortega M, "Angioyrndion II regulates the synthesis of proinflammatory cytokines and chemokines in the kidney", Kid Int suppul, 82, pp.12~22 (2002)
- Ahn EK, "Anti-inflammatoryand anti-angiogenic activities of Gastrodia elata Blume", J Ethnophamacol, 110, pp.476~482 (2007)
- Lirdprapamongkol K, "Vanillin suppresses in vitro invasion and in vivo metastasis of mouse breast cancer cells", Eur J Pharm Sci, 25, pp.57~65 (2005)
- Akagi K, "Modulating effects of ellagic acid, vanillin and quercetin in a rat medium term multi-organ carcinogenesis model", Cancer Lett, 94, pp.113~121 (1995)
- Kaynar K, "Amikacin-induced nephropathy: Is there any protective way", Ren Fail, 29, pp.23~27 (2007)
- Nam JH, "Effect of quality and quantity of dietary fat on status of tocopherol and lipid peroxidation of plasma tissue in rats", Korean J Nutr, 26, pp.566~577 (1993)
- Halliwell B, "Free radicals in biology and medicine" (1999), Oxford University Press
- Kang YH, "Effects of pine needle extract on enzyme activities of serum and liver and liver morphology in rats fed high fat diet", J Korean Soc Food Nutr, 25, pp.374~378 (1996)
- Zaitone S, "Pentoxifylline and melatonin in combination with pioglitazone ameliorate experimental non-alcoholic fatty liver disease", Eur J Pharmacol, 662, pp.70~77 (2011)
- Da Silveira M, "Trimetazidine and Nacetylcysteine in attenuating hind-limb ischemia and reperfusion injuries : Experimental study in rats", Int Angiol, 28, pp.412~417 (2009)