Mohania Dheeraj, Kansal Vinod K, Kruzliak Peter, Kumari Archana
1 Animal Biochemistry Division, National Dairy Research Institute (NDRI) , Karnal, Haryana, India .
Rejuvenation Res. 2014 Aug;17(4):325-33. doi: 10.1089/rej.2013.1537.
Aberrant crypt foci (ACF) and mucin-depleted foci (MDF) are pre-neoplastic lesions identified in the colon of carcinogen-treated rodents and in humans at high risk for colon cancer. The present study was carried out to divulge the protective potential of the probiotic Dahi containing Lactobacillus acidophilus LaVK2 and Bifidobacterium bifidum BbVK3 alone or in combination with piroxicam (PXC) on the development of early biomarkers of colorectal carcinogenesis in male Wistar rats administered 1,2-dimethylhydrazine (DMH). DMH was injected subcutaneously at the rate of 40 mg/kg body weight per animal twice a week for 2 weeks. A total of 120 male Wistar rats were randomly allocated to five groups, each group having 24 animals. The rats were fed with buffalo milk or probiotic supplement (20 grams) alone or as an adjunct with PXC in addition to a basal diet ad libitum for 32 weeks. Group I was offered buffalo milk (BM) and served as the control group. Group II was administered DMH along with BM and served as the DMH-control group; group III was administered BM-DMH-PXC, in which besides administering BM-DMH, PXC was also offered. Group IV was offered probiotic LaBb Dahi and DMH, and group V was offered both probiotic LaBb Dahi and PXC along with DMH. The rats were euthanized at the 8(th), 16(th), and 32(nd) week of the experiment and examined for development of ACF, aberrant crypts per ACF (AC/ACF), mucin-depleted foci (MDF), large MDF, and proliferating cell nuclear antigen (PCNA) labeling index. Administration of DMH in rats induced pre-neoplastic lesions (ACF and MDF) and increased the PCNA index in colorectal tissue. A significant (p<0.05) reduction in the number of ACF, AC/ACF, MDF, large MDF, and PCNA labeling index were observed in the probiotic LaBb Dahi group compared with the DMH control group. Feeding rats with LaBb Dahi or treatment with PXC diminished the initiation and progression of DMH-induced pre-neoplastic lesions and the PCNA index, and treatment with LaBb Dahi and PXC combined was significantly more effective. The dietary intervention of probiotics and PXC significantly protects against the development of CRC in the rat-DMH model. These observations suggest that probiotic LaBb Dahi alone or as an adjunct with PXC may have anti-neoplastic and anti-proliferative activities. Moreover, probiotic LaBb Dahi possesses the medicinal properties to prevent colorectal carcinogenesis.
异常隐窝灶（ACF）和黏蛋白缺失灶（MDF）是在致癌物处理的啮齿动物结肠以及患结肠癌高风险人群的结肠中发现的癌前病变。本研究旨在揭示含有嗜酸乳杆菌LaVK2和双歧双歧杆菌BbVK3的益生菌达希单独使用或与吡罗昔康（PXC）联合使用对给予1,2 - 二甲基肼（DMH）的雄性Wistar大鼠结直肠癌发生早期生物标志物发展的保护潜力。以每只动物40 mg/kg体重的剂量皮下注射DMH，每周两次，共2周。总共120只雄性Wistar大鼠随机分为五组，每组24只动物。大鼠除随意进食基础饮食外，单独给予水牛奶或益生菌补充剂（20克），或作为PXC的辅助剂，持续32周。第一组给予水牛奶（BM），作为对照组。第二组给予DMH和BM，作为DMH对照组；第三组给予BM - DMH - PXC，即除给予BM - DMH外，还给予PXC。第四组给予益生菌LaBb达希和DMH，第五组给予益生菌LaBb达希和PXC以及DMH。在实验的第8、16和32周对大鼠实施安乐死，并检查ACF的发展、每个ACF的异常隐窝数（AC/ACF）、黏蛋白缺失灶（MDF）、大MDF和增殖细胞核抗原（PCNA）标记指数。给大鼠注射DMH会诱发癌前病变（ACF和MDF）并增加结肠组织中的PCNA指数。与DMH对照组相比，益生菌LaBb达希组的ACF数量、AC/ACF、MDF、大MDF和PCNA标记指数显著（p<0.05）降低。给大鼠喂食LaBb达希或用PXC治疗可减少DMH诱导的癌前病变的起始和进展以及PCNA指数，联合使用LaBb达希和PXC治疗效果更显著。益生菌和PXC的饮食干预可显著预防大鼠 - DMH模型中结直肠癌的发生。这些观察结果表明，单独的益生菌LaBb达希或与PXC联合使用可能具有抗肿瘤和抗增殖活性。此外，益生菌LaBb达希具有预防结直肠癌发生的药用特性。
