Zoology Department, Faculty of Science, Ain Shams University, Cairo, Egypt.
Department of Immunology, Theodor Bilharz Research Institute, Giza, Egypt.
Environ Toxicol. 2019 Sep;34(9):1025-1033. doi: 10.1002/tox.22773. Epub 2019 May 14.
Hepatocellular carcinoma is considered one of the most prevalent and lethal malignancies worldwide. Chemotherapy with cytotoxic agents showed a low response rate with possible toxic effects. Recently, some emphases have been placed on the anticancer properties of bovine whey protein and its components, especially lactoferrin. The present study aimed to evaluate and compare the antihepatocarcinogenic activity of bovine whey protein concentrate (WPC, 300 and 600 mg/kg body weight) and lactoferrin (30 and 60 mg/kg body weight), orally and daily for 14 weeks, in the mice model of diethylnitrosamine (DEN)-induced hepatocarcinogenesis. The results showed that both WPC and lactoferrin (in a dose-dependent manner) alleviated significantly (P < .001) the elevation in serum markers of liver carcinoma and inflammation in the DEN-treated mice. Also, they exhibited a great amelioration in the livers' histological structure of the DEN-treated mice by 37.0% to 66.7%. In addition, they decreased significantly (P < .001) the hepatic DNA fragmentation in the DEN-treated mice by 23.1% to 32.7%. Only, the high doses of WPC and lactoferrin completely modulated the decrease in the activity of liver enzymic antioxidant defense system (catalase, glutathione peroxidase, and superoxide dismutase) and improved significantly (P < .01-.001) the concentration of hepatic reduced glutathione of the DEN-treated mice. Moreover, the high doses of WPC and lactoferrin reduced significantly (P < .05-.001) the elevation in the concentrations of hepatic active caspases 3, 8, and 9 of the DEN-treated mice. In conclusion, both WPC and lactoferrin were effective in inhibiting the hepatocarcinogenic activity of DEN in mice model through their ability to alleviate the hepatic inflammation and apoptosis.
肝细胞癌被认为是全球最普遍和最致命的恶性肿瘤之一。细胞毒性药物化疗的反应率低，且可能具有毒性作用。最近，人们对牛初乳蛋白及其成分（特别是乳铁蛋白）的抗癌特性给予了一些关注。本研究旨在评估和比较牛初乳蛋白浓缩物（WPC，300 和 600mg/kg 体重）和乳铁蛋白（30 和 60mg/kg 体重）的口服和每日抗二乙基亚硝胺（DEN）诱导的肝癌活性，为期 14 周。结果表明，WPC 和乳铁蛋白（呈剂量依赖性）均显著减轻（P<.001）DEN 处理小鼠血清肝癌标志物和炎症的升高。此外，它们使 DEN 处理小鼠肝脏的组织学结构得到了极大的改善，改善率为 37.0%至 66.7%。此外，它们还使 DEN 处理小鼠肝脏 DNA 片段化显著降低（P<.001），降低率为 23.1%至 32.7%。只有 WPC 和乳铁蛋白的高剂量完全调节了 DEN 处理小鼠肝脏酶抗氧化防御系统（过氧化氢酶、谷胱甘肽过氧化物酶和超氧化物歧化酶）活性的降低，并显著改善（P<.01-.001）了 DEN 处理小鼠肝脏还原型谷胱甘肽的浓度。此外，WPC 和乳铁蛋白的高剂量还显著降低（P<.05-.001）了 DEN 处理小鼠肝脏活性 caspase-3、8 和 9 浓度的升高。总之，WPC 和乳铁蛋白均能通过减轻肝炎症和凋亡来有效抑制 DEN 在小鼠模型中的肝癌发生活性。
