Histidine及carnosine抗acetaminophen誘發肝臟氧化損傷之動物研究

Protective Effects of Histidine and Carnosine on Acetamionphen-Induced Hepatoxicity in Balb/cA Mice

王家聆(Chia–Ling Wang)

指導教授 ： 徐成金

中山醫學大學/健康管理學院/營養學研究所/碩士(2005年)

https://doi.org/10.6834/CSMU.2005.00088

摘要

Carnosine與histidine是兩個胺基酸的衍生物。我們過去的研究證實這些化合物可增加肝臟中抗氧化酵素之活性，進而對肝臟有保護作用。因此，本研究進一步探討這些化合物抗acetaminophen (APAP)誘發Balb/cA小鼠肝臟毒性之影響。於飲水中添加低劑量0.8g/L之histidine或carnosine，分別為 (1)control組； (2)acetaminophen組 (APAP組)； (3)histidine組； (4)carnosine組，飲用4星期後，腹腔注射APAP (300mg/kg BW)並於20小時後犧牲，進行ALT、AST、TG、TC、lipid peroxidation level、glutathione (GSH)、glutathione peroxidase (GPx)、catalase、antithrombin-Ⅲ (AT-Ⅲ)、protein C、plasminogen、C反應蛋白 (CRP)、介白素-6 (IL-6)、腫瘤壞死因子 (TNF-α)及介白質-10 (IL-10)分析。結果顯示，APAP處理造成小白鼠之ALT及AST顯著上升(p＜0.05)，而攝取histidine及carnosine可顯著降低血漿中的ALT及AST。攝取這些化合物可顯著性增加GSH及CRP之濃度，且降低lipid oxidation level (p＜0.05)。另外，攝取carnosine可提高AT-Ⅲ及降低IL-6 (p＜0.05)，且攝取histidine會降低TNF-α和plasminogen (p＜0.05)。上述結果指出這些化合物可以保護肝臟抵抗acetaminophen所誘發的氧化損傷。

關鍵字

肌肽、組織胺酸、乙醯胺酚、肝毒性

並列摘要

Carnosine and histidine are two amino acids derivates. Our past study found these compounds exhibited antioxidant protection via increasing activity of associated enzymes. Thus, we further examined the effect of these compounds against acetaminophen induced liver toxicity in Balb/cA mice. These compounds at 0.8 g/L were added into drinking water for 4 weeks. Acetaminophen at 300 mg/Kg was given via intraperitoneal injection. alanine aminotransferase (ALT), aspartate aminotransferase (AST), TG, TC, lipid peroxidation level, glutathione (GSH), glutathione peroxidase (GPx), catalase, antithrombin-III (AT-III), protein C, plasminogen (PLG), CRP, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) were analyzed. Results showed that acetaminophen treatment significantly elevated ALT and AST (P<0.05), however, the intake of carnosine and histidine significantly reduced ALT and AST (P<0.05). The intake of these compounds significantly increased GSH, CRP concentration and catalase activities, and decreased lipid oxidation level (P<0.05). Furthermore, carnosine intake increased AT-III and reduced IL-6 (P<0.05); histidine intake decreased TNF-αand PLG (P<0.05). These results indicated that these compounds could protect liver against acetaminophen induced damage.

並列關鍵字

carnosine ； histidine ； acetaminophen ； liver toxicity

參考文獻

41.趙婉如 (2002) 探討大蒜精油對血小板凝集及凝血作用之影響. 私立靜宜大學. 食品營養系.

4. Moller, S. & Henriksen, J. H. (1996) Endothelins in chronic liver disease. Scand J Clin Lab Invest 56: 481-490.

5. Ahmed, M. B. & Khater, M. R. (2001) Evaluation of the protective potential of Ambrosia maritima extract on acetaminophen-induced liver damage. J Ethnopharmacol 75: 169-174.

7. Reilly, T. P., Bourdi, M., Brady, J. N., Pise-Masison, C. A., Radonovich, M. F., George, J. W. & Pohl, L. R. (2001) Expression profiling of acetaminophen liver toxicity in mice using microarray technology. Biochem Biophys Res Commun 282: 321-328.

8. Kasaoka, S., Tsuboyama-Kasaoka, N., Kawahara, Y., Inoue, S., Tsuji, M., Ezaki, O., Kato, H., Tsuchiya, T., Okuda, H. & Nakajima, S. (2004) Histidine supplementation suppresses food intake and fat accumulation in rats. Nutrition 20: 991-996.