Applied Microscopy

  • 제37권1호
  • /
  • Pages.1-10
  • /
  • 2007
  • /
  • 2287-5123(pISSN)
  • /
  • 2287-4445(eISSN)
한국현미경학회 (Korean Society of Microscopy)
권호 표지

Monocrotaline으로 유발된 흰쥐의 간독성에 대한 해독정기탕의 효과

Effect of Haedokjeongki-tang in Rat Liver after Monocrotaline Exposure

  • 발행 : 2007.03.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

MCT 유발 간독성 흰쥐에 해독정기탕의 투여가 시간경과에 따른 간세포의 항산화효소 활성변화, 세포사멸 억제와 간의 조직병리학적 변화에 미치는 영향을 조사하였다. 대조군은 생리식염수를 투여하였으며, 실험군은 해독정기탕 0.9 mL을 6시간, 24시간 간격으로 경구투여 하였다. 간기능의 지표가 되는 GPT 효소 활성은 해독정기탕 투여한 6시간 군에서 대조군에 비해 감소하였다. 항산화 효소인 SOD, catalase 활성도의 변화에 있어서도 6시간 실험군에서 변화를 보여주었고 24시간 경과 후에는 대조군과 실험군의 통계적인 유의성은 없었다. 간의 조직병리학적 관찰 결과 대조군은 심한 출혈, 간세포의 팽창과 중심정맥 내피세포의 파괴 현상이 뚜렷이 나타났으며, 24시간 경과 후에는 핵질의 응축과 사립체의 팽대현상이 현저하였다. 반면 해독정기탕 투여후 6시간 실험군은 일부 세포괴사와 세포사멸 보호 및 회복효과를 관찰하였다. 이상의 연구 결과로 보아 해독정기탕은 투여시간에 따라 간 기능회복 및 해독, 간세포의 항산화 활성변화, 세포사멸의 보호효과 약물로서 작용함이 사료된다.

Monocrotaline (MCT) is a pyrrolizidine alkaloid (PA) plant toxin that produces hapatotoxicity in humans and animals. To felt the hypothesis, we investigated the possible protective effects of Haedokjeongki-tang as an antioxidant against MCT-induced liver injury in rats. Cells with apoptotic morphology have been observed in the livers of animals exposed to Ph and Haedokjeongki-tang. Whether apoptosis occurs in the livers of MCT-treated animals and whether it is required for full manifestation of pathological changes is not known, To determine this, rats were treated with 100 mg MCT/kg, and apoptosis was detected by transmission electron microscopy and TUNEL assay. MCT produced apoptosis in the liver by 6 h after treatment and increased by 24 h. Administration of Haedokjeongki-tang did affect liver structure and inhibit apopotosis in MCT-induced liver injury. Upon light and electron microscopic examination, we observed that Haedokjeongki-tang improved the morphological and histopathological changes of the liver caused by MCT-induced injury. MCT caused a time-dependent release of GOT and GPT, a marker of liver injury. Furthermore, we observed with respect to antioxidants status, catalase and superoxide dismutase activity tended to be higher in the MCT-treated rats than in the Haedokjeongki-tang administered rats. Our finding showed that Haedokjeongki-tang administration partially reduced liver injury after MCT exposure.

키워드

참고문헌

  1. Baud L, Ardalliou R: Reactive oxygen species: production and role in the kidney. Am J Physiol 251 : 765-776, 1986
  2. Beers RJ, Sizer IWA: Spectrophotometric method for measuring the breakdown of $H_2O_2$ by catalase. J Biol Chem 195 : 133-140, 1952
  3. Brayan LC, Catherine MR, Jane FM, Niel CH, Patrica EG, Robert AR: Modes of cell death in rat liver after monocrotalin exposure. Toxicol Scien 77 : 172-182, 2004
  4. Copple BL, Banes A, Ganey PE, Roth RA: Anticoagulants prevent monocrotaline-induced hepatic parenchymal cell injury but not endothelial cell injury in the rat. Toxicol Appl Pharmacol 180 : 186-196, 2002 https://doi.org/10.1006/taap.2002.9394
  5. Copple BL, Ganey PE, Roth RA: Liver inflammation during monocrotaline hepatotoxicity. Toxicol 190 : 155-169, 2003 https://doi.org/10.1016/S0300-483X(03)00164-1
  6. Corcoran GB, Fix L, Jones issu DP, Moslen MT, Nicotera P, oberhammer FA, Buttyan R: Contemporary in toxicology. Apoptosis: molecular control point in toxicity. Toxicol Appl Pharmacol 128 : 169-181, 1994 https://doi.org/10.1006/taap.1994.1195
  7. Deng HL, Zhang JT: Anti-lipid peroxidative effect of ginsenoside Rb1 and Rg1. Chin Med J 104 : 395, 1991
  8. Gorden GJ, Coleman WB, Grisham JW: Bax-mediated apoptosis in the livers of rat after hepatectomy in the retrorsine model of hepatocellular injury. Hepatology 32 : 312-320, 2000 https://doi.org/10.1053/jhep.2000.9144
  9. Gujral JS, knight TR, Farhood A, Bajt ML, Jaeschke H: Mode of cell death after acetaminophen overdose in mice. Toxicol Sci 67 : 322-328, 2002 https://doi.org/10.1093/toxsci/67.2.322
  10. Hongo M, Mawatari E, Sakai A, Ruan Z, Koizumi T, Terasawa F, Yazaki Y, Kinoshita O, Ikeda U, Shibamoto T: Effects of nicorandil on monocrotaline-induced pulmonary arterial hypertension in rats. J Cardiovasc Pharmacol 46 : 452-458, 2005 https://doi.org/10.1097/01.fjc.0000176728.74690.09
  11. Huxtable RJ: Human health implications of PA and herbs containing them. In Toxicant of plant Origin 1 : 41-86, 1989
  12. Jaeschke H, Fisher MA, Lawson JA, Simmons CA, Farhood A, Jones DA: Activation of caspase 3-like proteases is essential for TNF-alpha induced hepatic parenchymal cell apoptosis and neutrophil-mediated necrosis in a murine endotoxin shock model. J Immunol 160 : 3480-3486, 1998
  13. Janssen YMW, Van Houten B, Boom PJA, Mossman BT: Biology of disease: cell and tissue responses to oxidative damage. Lab Invest 69 : 261-274, 1993
  14. Kim SY, Kim HP, Lee MK, Byun SJ, Kim SH, Han HM. Moon A, Huh M, Kim YC: The effect of betaine on the $CCl_4$-induced hepatoxicity in rats. Yakhak Hoeji 37 : 538-543, 1993
  15. Mattocks AR, White INH: Estimation of metabolites of PA in animal tissues. Anal Biochem 38 : 529-535, 1970 https://doi.org/10.1016/0003-2697(70)90478-1
  16. Meyrick BW, Gamble, Reid: Development of crotalaria pulmonary hypertention: hemodynamic and structural study. Am J Physiol 239 : 692-702, 1980
  17. Reitman FA, Berger ML, Shertzer HG: Studies on calcium transport during carbon tetrachloride mediated hepatotoxicity in mice. Biochem Pharmacol 37 : 4584-4586, 1988 https://doi.org/10.1016/0006-2952(88)90678-8
  18. Schoental R, Head M: Pathological changes in rats as a result of treatment with monocrotaline. Brit J Cancer 9 : 229-237, 1955 https://doi.org/10.1038/bjc.1955.19
  19. Schultz AE, Roth RA: Chronic pulmonary hypertension: The monocrotaline model and involvement of the hemostatic system. J Toxicol Environ Health B Crit Rev 1 : 271-346, 1998 https://doi.org/10.1080/10937409809524557
  20. Schumann J, Wolf D, Pahl A, Brune K, Papadopoulos T, van Rollijen N, Tiegs G: Importance of Kupffer cells for T-cell dependent liver injury in mice. Am J Pathol 157 : 1671-1683, 2000 https://doi.org/10.1016/S0002-9440(10)64804-3
  21. Shi J, Aisaki K, Ikawa Y, Wake K: Evidence of hepatocyte apoptosis in rat liver after the administration of carbon tetrachloride. Am J Pathol 153 : 515-525, 1998 https://doi.org/10.1016/S0002-9440(10)65594-0
  22. Willson DW, Segall HJ, Pan LC, Lame MW, Estep JE, Morin D: Mechanism and pathology of monocrotaline pulmonary toxicity. Crit Rev Toxicol 22 : 307-325, 1992 https://doi.org/10.3109/10408449209146311
  23. Yacoub LK, Fogt F, Griniuvience B, Nanji AA: Apoptosis and bcl-2 protein expression in experimental alcoholic liver disease in the rat. Alcohol Clin Exp Res 19 : 854-859, 1995 https://doi.org/10.1111/j.1530-0277.1995.tb00958.x