Rashid Summya, Ali Nemat, Nafees Sana, Hasan Syed Kazim, Sultana Sarwat
Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard University, New Delhi, India.
Toxicol Int. 2013 Sep;20(3):227-34. doi: 10.4103/0971-6580.121676.
The present study was designed to investigate the chemo preventive efficacy of bee propolis (BP) against diethylnitrosamine (DEN) initiated and ferric nitrilotriacetate (Fe-NTA) promoted renal carcinogenesis in Wistar rats. Chronic treatment of Fe-NTA induced oxidative stress, inflammation and cellular proliferation in Wistar rats. BP is a resinous material collected by bees from various plants which has been used from centuries in folk medicine.
Renal cancer was initiated by single intraperitoneal injection of N-nitrosodiethylamine (DEN 200 mg/kg body weight) and promoted by twice weekly administration of Fe-NTA 9 mg Fe/kg body weight for 16 weeks. The chemo preventive efficacy of BP was studied in terms of lipid peroxidation (LPO), renal anti-oxidant armory such as catalase, superoxide dismustase, glutathione S-transferase, glutathione peroxidase, glutathione reductase and glutathione (GSH), serum toxicity markers, cell proliferation, tumor suppressor protein and inflammation markers.
Administration of Fe-NTA enhances renal LPO, with concomitant reduction in reduced GSH content and antioxidant enzymes. It induces serum toxicity markers, viz., blood urea nitrogen, creatinine and lactate dehydrogenase. Chemo preventive effects of BP were associated with upregulation of antioxidant armory and down regulation of serum toxicity markers. BP was also able to down regulate expression of proliferative cell nuclear antigen, cyclooxygenase-2, tumor necrosis factor-alpha and upregulated p53 along with induction of apoptosis. Histopathological changes further confirmed the biochemical and immunohistochemical results.
These results provide a powerful evidence for the chemo preventive efficacy of BP against renal carcinogenesis possibly by modulation of multiple molecular pathways.
本研究旨在探讨蜂胶（BP）对二乙基亚硝胺（DEN）启动及次氮基三乙酸铁（Fe-NTA）促进的Wistar大鼠肾癌发生的化学预防作用。Fe-NTA的长期处理可诱导Wistar大鼠产生氧化应激、炎症和细胞增殖。BP是蜜蜂从各种植物中采集的树脂状物质，在民间医学中已使用了数百年。
通过单次腹腔注射N-亚硝基二乙胺（DEN，200mg/kg体重）启动肾癌，并通过每周两次给予Fe-NTA（9mg铁/kg体重）持续16周来促进肾癌发生。从脂质过氧化（LPO）、肾脏抗氧化物质如过氧化氢酶、超氧化物歧化酶、谷胱甘肽S-转移酶、谷胱甘肽过氧化物酶、谷胱甘肽还原酶和谷胱甘肽（GSH）、血清毒性标志物、细胞增殖、肿瘤抑制蛋白和炎症标志物等方面研究BP的化学预防效果。
给予Fe-NTA可增强肾脏LPO，同时降低还原型GSH含量和抗氧化酶活性。它还诱导血清毒性标志物，即血尿素氮、肌酐和乳酸脱氢酶。BP的化学预防作用与抗氧化物质上调及血清毒性标志物下调有关。BP还能够下调增殖细胞核抗原、环氧化酶-2、肿瘤坏死因子-α的表达，并上调p53以及诱导细胞凋亡。组织病理学变化进一步证实了生化和免疫组化结果。
这些结果为BP对肾癌发生的化学预防作用提供了有力证据，可能是通过调节多种分子途径实现的。
