Wills P J, Suresh V, Arun M, Asha V V
Molecular Ethnopharmacology Lab, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram 695014, Kerala, India.
Chem Biol Interact. 2006 Dec 1;164(1-2):25-38. doi: 10.1016/j.cbi.2006.08.021. Epub 2006 Sep 1.
The antiangiogenic effect of Lygodium flexuosum extract was evaluated in Wistar rats intoxicated with N-nitrosodiethylamine (NDEA) in preventive and curative models. In preventive groups, NDEA was administered for 20 weeks. Daily doses of L. flexuosumn-hexane extract (200mg/kg) started 1 week before the onset of NDEA intoxication and continued for 20 weeks. In curative animals, NDEA was administered for 20 weeks followed by treatment with the n-hexane extract of L. flexuosum for 28 days. Rats intoxicated with NDEA had elevated levels of serum gamma-GT, AST, ALT, LDH levels and hepatic MDA and decreased levels of hepatic GSH. When treated with L. flexuosum extract had normal levels of gamma-GT, AST, ALT, LDH levels, hepatic MDA and GSH. NDEA administered rat liver showed an overexpressed levels of angiopoietins 1 (Ang-1) and 2 (Ang-2) and its receptor Tie-2 mRNA. L. flexuosum extract treatment significantly (p<or=0.05) reduced the levels of Ang-1 and Ang-2 and Tie-2 in rat livers evidenced by RT-PCR. Immunohistochemical analysis showed that vascular endothelial growth factor (VEGF) was overexpressed and localized around periportal area of liver sections intoxicated with NDEA and its overexpression was effectively reduced by the treatment with L. flexuosum extract. Histopathological observations also substantiated NDEA-induced hepatotoxicity and the effect was significantly (p<or=0.05) reduced by L. flexuosum extract treatment. Thus, L. flexuosum extract at a dose of 200mg/kg effectively reversed the hepatotoxicity induced by N-nitrosodiethylamine in both experimental models.
在预防性和治疗性模型中，对用N-亚硝基二乙胺（NDEA）中毒的Wistar大鼠评估了海金沙提取物的抗血管生成作用。在预防组中，给予NDEA 20周。海金沙正己烷提取物的每日剂量（200mg/kg）在NDEA中毒开始前1周开始，并持续20周。在治疗组动物中，给予NDEA 20周，随后用海金沙正己烷提取物治疗28天。用NDEA中毒的大鼠血清γ-GT、AST、ALT、LDH水平以及肝脏MDA水平升高，肝脏GSH水平降低。当用海金沙提取物治疗时，γ-GT、AST、ALT、LDH水平、肝脏MDA和GSH水平恢复正常。给予NDEA的大鼠肝脏显示血管生成素1（Ang-1）和2（Ang-2）及其受体Tie-2 mRNA的表达上调。海金沙提取物治疗通过RT-PCR显著（p≤0.05）降低了大鼠肝脏中Ang-1、Ang-2和Tie-2的水平。免疫组织化学分析表明，血管内皮生长因子（VEGF）在NDEA中毒的肝脏切片门静脉周围区域过度表达，而海金沙提取物治疗有效降低了其过度表达。组织病理学观察也证实了NDEA诱导的肝毒性，海金沙提取物治疗显著（p≤0.05）降低了这种作用。因此，200mg/kg剂量的海金沙提取物在两种实验模型中均有效逆转了N-亚硝基二乙胺诱导的肝毒性。
