Kashimoto Naoki, Ishii Satomi, Myojin Yuki, Ushijima Mitsuyasu, Hayama Minoru, Watanabe Hiromitsu
Health Care Institute, Wakunaga Pharmaceutical Co Ltd., Hiroshima 739-1195.
Oncol Lett. 2010 Jan;1(1):63-68. doi: 10.3892/ol_00000011. Epub 2010 Jan 1.
The present study investigated whether a water-soluble extract from the culture medium of Ganoderma lucidum (Reishi) mycelia (MAK) is able to protect the small intestine against damage induced by anti-cancer drugs. Six-week-old male B6C3F1/Crlj mice were fed a basal diet (MF) alone or with various doses of MAK or Agarics blazei Murrill (AGA) beginning one week before treatment with the anti-cancer drugs. Mice were sacrificed 3.5 days after injection of the anti-cancer drug, the small intestine was removed and tissue specimens were examined for the regeneration of small intestinal crypts. In experiment 1, the number of regenerative crypts after the administration of 5-fluorouracil (5FU) intravenously (250 mg/kg) or intraperitoneally (250 or 500 mg/kg) was compared after treatment with MAK or AGA. MAK protected against 5FU-induced small intestinal injury whereas AGA did not. In experiment 2, we investigated the protective effect of MAK against small intestinal injury induced by the anti-cancer drugs: UFT (tegafur with uracil; 1,000 mg/kg, orally), cisplatin (CDDP; 12.5 and 25 mg/kg, intraperitoneally), cyclophosphamide (CPA; 250 mg/kg, orally) and gefitinib (Iressa; 2,000 and 4,000 mg/kg, orally). UFT and CDDP decreased the number of regenerative crypts, but treatment with MAK attenuated the extent of UFT- or CDDP-induced small intestinal injury. CPA or Iressa plus MAK up-regulated crypt regeneration. The present results indicate that MAK ameliorates the small intestinal injury caused by several anti-cancer drugs, suggesting that MAK is a potential preventive agent against this common adverse effect of chemotherapy.
本研究调查了灵芝菌丝体培养基的水溶性提取物(MAK)是否能够保护小肠免受抗癌药物诱导的损伤。六周龄雄性B6C3F1/Crlj小鼠在接受抗癌药物治疗前一周开始单独喂食基础饲料(MF),或添加不同剂量的MAK或巴西蘑菇(AGA)。在注射抗癌药物3.5天后处死小鼠,取出小肠并检查组织标本中小肠隐窝的再生情况。在实验1中,比较了静脉注射(250 mg/kg)或腹腔注射(250或500 mg/kg)5-氟尿嘧啶(5FU)后,经MAK或AGA处理的再生隐窝数量。MAK可保护小鼠免受5FU诱导的小肠损伤,而AGA则不能。在实验2中,我们研究了MAK对以下抗癌药物诱导的小肠损伤的保护作用:优福定(替加氟与尿嘧啶;1000 mg/kg,口服)、顺铂(CDDP;12.5和25 mg/kg,腹腔注射)、环磷酰胺(CPA;250 mg/kg,口服)和吉非替尼(易瑞沙;2000和4000 mg/kg,口服)。优福定和顺铂减少了再生隐窝的数量,但MAK治疗减轻了优福定或顺铂诱导的小肠损伤程度。环磷酰胺或吉非替尼加MAK上调了隐窝再生。目前的结果表明,MAK可改善几种抗癌药物引起的小肠损伤,提示MAK是预防化疗这种常见不良反应的潜在药物。