於SD雌性大鼠模式之下以病理角度評估巴西磨菇亞急性毒性

Subacute Toxicity Assessment of Agaricus Blazie Murrill Extract by Pathologic Determiniation in Female SD Rats

施勇綸(Yung-Luen Shih) ； 吳龍源(Ling-Yuan Wu) ； 周建聖(Jason Chou) ； 吳銘芳(Ming-Fang Wu) ； 呂旭峰(Hsu-Feng Lu)

《傳統醫學雜誌》 25卷1期 (2014/10) Pp. 1-16

摘要

維他命B12僅存在於動物性食品，而植物性卻闕如，所幸蘑菇含量豐富，因此素食者可仰賴蘑菇補充維他命B12。近百年來，就如同人類的食物與飮料般，蘑菇被認爲是人類食物的營養品，最後更演變成醫療用途。2012年全球五年內被診斷出罹患癌症人口高達32,600,000，當年度8,200,000人死於癌症，新產生病例亦高達14,100,000。中國傳統醫學療法可增加化學與放射療法的敏感性，減少副作用與併發症，甚至改善生活品質與延長餘命。在玲瑯滿目種類的蘑菇中最令人感興趣的是巴西蘑菇，除了逐漸大量成爲食物補充品之外，某些硏究指出巴西蘑菇可以抗腫瘤、抗病毒、抗感染、降血糖、降血脂與降血壓。儘管巴西蘑菇優點甚多，食物安全性評估卻鮮少。本硏究將7週齢雌性SD大鼠40隻分成四組，每組10隻，四組包括控制組、低劑量組（15mg/Kg）、中劑量組（50mg/Kg）與高劑量組（250mg/Kg）。以分組劑量各別連續28天口服餵食，觀察其亞急性毒性反應。28天連續投與終了後動物飼料用量大致正常，動物外觀非常正常，未觀察到動物有任何虛弱的表現，動物體重持續穩定增加中，從實驗開始到結束都沒有動物死亡。就病理組織學的檢查。實驗組經肝切片結果顯示中央靜脈血管無充血現象，肝細胞亦無與發炎有關的囊腫或壞死殘片。實驗組腎臟腎元之腎小管與腎小球排列正常。脾臟即使經由高濃度劑量餵食，脾臟的紅白髓區均正常大小，因此所有實驗與對照組之脾臟皆無中毒特徵。因此，巴西蘑菇膠囊高、中、低劑量皆未觀察到有任何肝、腎、脾具顯著病變。因此雌性SD大鼠投予試驗物質「巴西蘑菇膠囊」在250mg/kg可當成「不造成任何不良副作用的劑量」（No Observed Adverse Effect Level, NOAEL）。

關鍵字

亞急性毒性反應 ； 不造成任何不良副作用劑量

並列摘要

Mushrooms are unique in that they contain Vitamin B 12, something that vegetables can't produce at all. Since B 12 is mainly of animal origin, deficiency is commonly associated with vegetarian diets. For many centuries, mushrooms were used as nutrients in the human diet, as agents of fermentation in the production of food and drink, and finally as medicine. There were 14.1 million new cancer cases, 8.2 million cancer deaths and 32.6 million people living with cancer (within 5 years of diagnosis) in 2012 worldwide. Traditional Chinese medicine (TCM) has great advantages in terms of increasing the sensitivity of chemo- and radio-therapeutics, reducing the side effects and complications associated with chemotherapy and radiotherapy, and improving patient quality of life and survival time. In a variety of different species of mushrooms, interest in the use of ＂Agaricus blazei＂ Murrill (ABM) and/or their extracts as dietary supplements has increased significantly, in part because of studies that have confirmed their antitumor, anticarcinogenic, antiviral, antiinflammatory, hypoglycemic, hypocholesterolemic, and antihypertensive effects. Although the ABM is with numerous benefits, the food safety assessment is absent. Female SD rats aged 7 weeks of age were randomized and allocated into control (group 1) and experimental (second to fourth groups) groups of ten animals each. Groups 2, 3 and 4 were orally administered low (15 mg/Kg), medium (50 mg/Kg) or high (250 mg/Kg) doses of ABM daily and separately for 28 days to observe the subacute toxicology. At the end of the 28-day period, histopathological examinations by H&E stain were performed for the kidney, liver and spleen. The overall feed consumption of animals receiving ABM was not statistically significantly different from that of the control groups. There were no mortalities nor emaciation during the course of study. Weekly mean body weight and body weight gain for all groups that consumed ABM were comparable to the control values. Histopathological examination of liver sections from rats treated with different concentrations of ABM revealed nonsignificant hepatocellular necrosis in centrilobular regions, without any signs of vascular or inflammatory changes. Normal histology of the glomerulus and tubules was found in kidney tissue of rats that received control, and ABM treatment. These was no micronodular lymphoid infiltrate located in white pulp, nor variable red pulp infiltration, marginal zone differentiation, or follicular replacement by neoplastic cells in spleen. There were no significant changes in the liver, kidney and spleen visually. These results suggest that the no-observed-adverse-effect level (NOAEL) of the extract for female SD rats is considered to be 250 mg/kg/day.

並列關鍵字

Agaricus blazei Murill ； No Observed Adverse Effect Level