獼猴桃屬植物對四氯化碳誘發大鼠急性肝損傷之保護作用

全文

(1)189. 1,2. 1. 1. 3. 1. 1. 2. 3. (Actinidia latifolia (Gardn. & Champ.) (A. chinensis PLANCH var. setosa Li). Merr.). (A. collosa Lindl.). (A. rubricaulis Dunn). 50%. 1. 24. sGOT. sGPT. (Actinidia rubricaulis Dunn). (0.1. 0.5 g/kg). sGOT. (p < 0.001) SOD. (p <. 0.01). SOD. 2005;10:189-95. SOD. Silybum marianum L. Gaertn. silybin. [1,2] CCl 4. p-. isosilybin. silydianin. silychristine SOD. 450 (cytochrome p-450) P-450. (CCl 3 • ). glutathione (GSH) [9]. dismutase (SOD). [3,4]. (Actinidia chinensis PLANCH). [5,6] GOT. GPT (actinidine). (silymarin). [7,8]. Silymarin. (emodin). β-. (zeatin) (β-sitosterol). (tanin) 404. superoxide. 91. 2005. 1. 13. 2005. 7. 19. vitamin B. (vitamin C) (actinidia. 2005. 7. 12. chinensis polysaccharide. ACPS).

(2) 190. (A. chinensis P LANCH var.. SOD kits. Art.ORD04 (. ). setosa Li) [10]. (CCl 4) (A.. latifolia (Gardn. & Champ.) Merr.). (A.. chinensis PLANCH var. setosa Li). (A.. rubricaulis Dunn). (A. collosa Lindl.). 6. 10 AL. AR. AC. (0.1. 0.5. ACS. 1.0 g/kg). silymarin (200 mg/kg in 1% CMC) 1. CCl4 (1.5 mL/kg in 20%). olive oil [11]. CCl 4. oil. olive 24 (3000rpm. 50%. 4. 10. ). serum serum. glutamic-oxalocetic transaminase (sGOT) glutamic-pyruvic transaminase (sGPT). 1 10% ( (. ACS). (. AC). (. AL) AR) 4. 3000. 10. rpm. sGOT [12,13]. sGOT. sGPT. Reitman [15,16]. & Frankel [14] 50%. 72. (SOD) SOD Assay 50%. (. sGPT. 0.5 g. 0.5 mL. normal saline. 0.9%. EtOH ext.). 300 µL 1.8 mL. 4. 15. 20 µL. 120 µL 0.1M phosphate buffer (CAPS Sprague-Dawley (SD). (200 to 250. 40 mmol/L. g/BW). EDTA 0.94 mmol/L 5 µL. (. 21. 1. 12. ). ( ). (Ion reverse water. Millipore. USA). pH7.0) 340 µL Mixed. 2-(4Substrate (Xanthine 0.05 mmol/L iodophenyl)3-(4-nitrophenol)-5-phenyltetrazolium Xanthine. chloride (I.N.T) 0.025 mmol/L). 505 nm. Oxidase 37. 30 3. (carbon tetrachloride Merck) ). Silymarin. Sigma. Ethyl Ether Randox. ALT (GPT) kits Art.AS483. SOD. I.N.T. Osaka kits. [17]. (formalin. Art.J16651. Protein kits. SOD Total Protein Assay. AST (GOT). Art.K83001. 0.5 g saline. (U) U/mg protein 0.5 mL 0.9% 50 µL. normal. 350 µL.

(3) 191. (AL) 50%. (AR) 50%. silymarin. sGOT. sGPT. (n = 10). *p < 0.05 (. 0.01. CCl4. (AC) 50% (n = 10). CCl4 0.001 (. ). normal saline. Biuret reagent. (Sodium hydroxide 100 mmol/L. Na-K-tartrate 16. Potassium iodide 15 mmol/L. CCl4. **p <. silymarin. sGOT. *p < 0.05 (. *p < 0.05. ). sGPT. (n = 10). mmol/L. ***p < 0.001 (. silymarin sGOT. sGPT. (n = 10). CCl4. ). (ACS) 50%. silymarin. sGOT. sGPT **p < 0.01. ***p <. ). 1. 10% HE. Cupric. sulphate 6mmol/L) 550 nm. 25 Jonker. 15 protein standard. [19]. (6.0 g/dL). Blank reagent (Sodium hydroxide 100 mmol/L. (F) protein. 0. Na-K-tartrate 16 mmol/L) (mg/g tissue) [18]. total. 0. (absent). 2. (weak). (moderate). 4. SPSS. 4. 1. (trace) 3 (severe).

(4) 192. (AR) 50%. Numberical score of ballooning degeneration. Numberical score of Numberical score of hepatitis hepatocytes necrosis Normal 0.00 0.00 0.00 0.00 1.00 0.00 CCl4 (20%) 3.00 0.00 3.00 0.00 3.00 0.00 CCl4 + silymarin (200 mg/kg) 2.00 0.00*** 2.30 0.34 2.00 0.00*** CCl4 + AR (0.1 g/kg) 2.60 0.22 3.00 0.00 2.80 0.13 CCl4 + AR (0.5 g/kg) 2.30 0.21 3.00 0.00 2.50 0.17 CCl4 + AR (1.0 g/kg) 2.10 0.10* 3.00 0.00 2.40 0.16* AR = A. rubricaulis Dunn. Data presented as mean SEM. *p < 0.05, ***p < 0.001 as compared with the CCl4 group (Non-parametric Kruskal-Wallis following by Mann-Whitney U test). Group. CCl4 sGPT 0.001). sGOT. Silymarin AC. sGOT (p <. (0.1. 0.5 g/kg). sGOT (p < 0.001). CCl4 SOD. Silymarin. SOD. 50%. 0.05). SOD. g/kg). (p <. (1.0. 0.5. (p < 0.01). (AR) 50% SOD ###. (n = 10) < 0.05. **p < 0.01 (. p < 0.001 (. CCl4. control. ). *p. ). silymarin (1.0g/kg) (One-Way ANOVA). Scheffe's. (. ). multiple range test p < 0.05. CCl4 sGPT 0.05). sGOT. Silymarin AL. sGOT (p < 0.05) CCl4. sGPT. sGOT. Silymarin. (p < 0.05). sGOT. ACS. sGPT. sGPT (p < 0.05) CCl4. sGPT. Silymarin. 0.001). sGPT (p < 0.05). sGOT (p < 0.001) (p < 0.05). [20,21]. sGOT (p <. (Actinidia rubricaulis var. coriacea). sGOT sGOT (p < [22]. AR AR. sGPT. [23] chinensis polysaccharide. (Actinidia ACPS) [24]. ACPS.

(5) 193. [25] SOD [26] [1]. ( CMU93-GCC-09. (sGOT). (sGPT). (Zone 3). CCl 4. (Cytochrome) p-450 (CCl 3 • ). [4-6] Cytochrome P-450. (isozyme. CYP 2E1) [27]. (ALT). [28] sGOT. sGOT. sGPT. sGPT. 50% (0.1. 0.5. 1.0 g/kg) (0.1. GMU94-060). 0.5 g/kg). 50% CCl4 (p. sGOT 0.001). 1. Recknagel RO. Carbon tetrachloride hepatotoxicity. [Review] Pharmacol Rev 1967;19:145-208. 2. Poli G. Liver Damage due to free radicals. [Review] Br Med Bull 1993;49:604-20. 3. Reynolds ES, Ree HJ. Liver parenchymal cell injury. VII. Membrane denaturation following carbon tetrachloride. Lab Invest 1971;25:269-78. 4. Akahori A, Masui M, Ando M. Change of serum glutamic oxaloacetic transaminase activities after administration of carbon tetrachloride to mice. Chem Pharm Bull (Tokyo) 1978;26:2316-20. 5. Lowery K, Glende EA, Recknagel RO. Destruction of liver microsomal calcium pump activity by carbon tetrachloride and bromotrichloromethane. Biochem Pharmacol 1981;30:135-40. 6. Waller RL, Glende EA Jr, Recknagel RO. Carbon tetrachloride and bromotrichloromethane toxicity. Dual role of covalent binding of metabolic cleavage products and lipid peroxidation in depression of microsomal calcium sequestration. Biochem Pharmacol 1983;32: 1613-7. 7. Mitchell JR, Jollow DJ, Potter WZ, et al. Acetaminophen-induced hepatic necrosis. . Protective role of glutathione. J Pharmacol Exp Ther 1973;187: 211-7. 8. Black M. Acetaminophen hepatotoxicity. [Review] Gastroenterology 1980;78:382-92. 9. Hjelle JJ, Klaassen CD. Glucuronidation and biliary excretion of acetaminophen in rats. J Pharmacol Exp Ther 1984;228:407-13. 10.. BALB 4 SOD. (0.2 g/kg. ). 1994:34 11.. [29] SOD SOD. 1997:117-8 12.Huang TC. Flora of Taiwan. Taipei, Editiorial Committee of the Flora of Taiwan, Second Edition, Volumn Two, 1996:656-61 13. 2000:27-30.

(6) 194. 14. Reitman S, Frankel S. A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol 1957;28:56-63. 15.Bergmeyer HU, Horder M, Rej R. International Federation of Clinical Chemistry (IFCC) Scientific Committee, Analytical Section: approved recommendation (1985) on IFCC methods for the measurement of catalytic concentration of enzymes. Part 3. IFCC method for alanine aminotransferase (Lalanine: 2-oxoglutarate aminotransferase, EC 2.6.1.2). J Clin Chem Biochem 1986;24:481-95. 16.Bergmeyer HU, Horder M, Rej R. International Federation of Clinical Chemistry (IFCC) Scientific Committee, Analytical Section: approved recommendation (1985) on IFCC methods for the measurement of catalytic concentration of enzymes. Part 2. IFCC method for aspartate aminotransferase (Laspartate: 2-oxoglutarate aminotransferase, EC 2.6.1.1). J Clin Chem Biochem 1986;24:497-510. 17. Woolliams JA, Wiener G, Anderson PH, et al. Variation in the activities of glutathione peroxidase and superoxide dismutase and in the concentration of copper in the blood in various breed crosses of sheep. Res Vet Sci 1983;34:253-6. 18.Henry RJ, Cannon DC, Winkelman JW. Clinical Chemistry, Principles and Techniques. Hagerstown, Md. Medical Dept.: Harper&Row, 1974. 19.Jonker AM, Dijkhuis FW, Boes A, et al. Immunohistochemical study of extracellular matrix in. acute galactosamine hepatitis in rats. Hepatology 1992; 15:423-31. 20. 1996;2:15-6 21. 2001;18:22-3 22. 1998;34:4-8 23. 1986;8:54 24. 1989;5:182-5 25. 1995;16:12-4 26. 1999;2112-6 27. Moslen MT. Toxic responses of the liver. In: Klassen CD, ed. Casarett & Doull's Toxicology: The Basic Science of Poisons, New York: McGraw-Hill Co., Inc., 1996:403-16. 28. 2003;23:351-2 29. Manno M, Bertazzon A, Burlina A, et al. Interaction of low doses of ionizing radiation and carbon tetrachloride on liver superoxide dismutase and glutathione peroxidase in mice. Enzyme 1985;34:107-12..

(7) 195. Hepatoprotective Effect of Four Species of Actinidia on Acute Liver Damage Induced by Carbon Tetrachloride in Rats 1,2. 1. 1. 3. 1. Jung-Chun Liao , Hao-Yuan Cheng , Kun-Hung Lin , Jin-Bin Wu , Wen-Huang Peng 1. 2. 3. Graduate Institute of Chinese Pharmaceutical Sciences, Center of General Education, Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, Taiwan.. Purpose. The present study was designed to evaluate the hepatoprotective effect of four Taiwan species of Actinidia on acute liver damage induced by carbon tetrachloride (CCl4) in rats. Methods. The extracts of four Actinidia species, Actinidia latifolia (Gardn. & Champ.) Merr. (abrr. AL), A. chinensis PLANCH var. setosa Li (ACS), A. rubricaulis Dunn (AR), and A. collosa Lindl. (AC) were orally administered to rats at three doses (0.1, 0.5, 1.0 g/kg). Liver damage was induced by CCl4 via an intraperitoneal injection one hour later. Twentyfour hours after CCl4 had been injected, the rats were anaesthetized with ether and blood samples were collected via carotid. The blood was centrifuged at 3000 rpm for 10 minutes and the amounts of serum glutamic-oxalocetic transaminase (sGOT), and serum glutamic-pyruvic transaminase (sGPT) were determined. The hepatoprotective effect of the four extracts in CCl4-induced injuries were judged by morphological and biochemical observation. Results. At low doses (0.1, 0.5 g/kg), AR and AC inhibited the CCl4-induced liver injury. AR and AC significantly decreased the CCl4-induced increase of sGOT level (p < 0.001) and AR (0.1 g/kg) decreased the CCl4-induced increase of sGPT level (p < 0.05). At high doses (0.5, 1.0 g/kg), AR increased SOD activities in the liver (p < 0.01), thereby protecting the liver from hepatocytes necrosis. Conclusions. AR and AC seem to inhibit CCl4-induced acute liver injury whereas AL and ACS do not. The mechanism by which AR inhibits liver damage seems to be related to the AR-induced increase in SOD in liver. ( Mid Taiwan J Med 2005;10:189-95 ). Key words actinidia, acute liver damage, hepatoprotection, SOD. Received : 13 January 2005.. Revised : 12 July 2005.. Accepted : 19 July 2005. Address reprint requests to : Wen-Huang Peng, Graduate Institute of Chinese Pharmaceutical Sciences, China Medical University, 91 Hsueh-Shih Road, Taichung 404, Taiwan..

(8)