Yongvanit Puangrat, Pinlaor Somchai, Bartsch Helmut
Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
Parasitol Int. 2012 Mar;61(1):130-5. doi: 10.1016/j.parint.2011.06.011. Epub 2011 Jun 17.
Chronic inflammation induced by liver fluke (Opisthorchis viverrini) infection is the major risk factor for cholangiocarcinoma (CCA) in Northeastern Thailand. Increased levels of proinflammatory cytokines and nuclear factor kappa B that control cyclooxygenase-2 and inducible nitric oxide activities, disturb the homeostasis of oxidants/anti-oxidants and DNA repair enzymes, all of which appear to be involved in O. viverrini-associated inflammatory processes and CCA. Consequently oxidative and nitrative stress-related cellular damage occurs due to the over production of reactive oxygen and nitrogen species in inflamed target cells. This is supported by the detection of high levels of oxidized DNA and DNA bases modified by lipid peroxidation products in both animal and human tissues affected by O. viverrini-infection. Treatment of opisthorchiasis patients with praziquantel, an anti- trematode drug was shown to reduce inflammation-mediated tissue damage and carcinogenesis. The principal mechanisms that govern the effects of inflammation and immunity in liver fluke-associated cholangiocarcinogenesis are reviewed. The validity of inflammation-related biomolecules and DNA damage products to serve as predictive biomarkers for disease risk evaluation and intervention is discussed.
肝吸虫（麝猫后睾吸虫）感染引起的慢性炎症是泰国东北部胆管癌（CCA）的主要危险因素。促炎细胞因子和控制环氧化酶-2及诱导型一氧化氮活性的核因子κB水平升高，扰乱了氧化剂/抗氧化剂和DNA修复酶的稳态，所有这些似乎都参与了麝猫后睾吸虫相关的炎症过程和胆管癌。因此，由于炎症靶细胞中活性氧和氮物种的过度产生，发生了氧化和硝化应激相关的细胞损伤。在受麝猫后睾吸虫感染的动物和人类组织中检测到高水平的氧化DNA和被脂质过氧化产物修饰的DNA碱基，这支持了上述观点。用抗吸虫药吡喹酮治疗肝吸虫病患者可减少炎症介导的组织损伤和致癌作用。本文综述了在肝吸虫相关胆管癌发生过程中炎症和免疫作用的主要机制。讨论了炎症相关生物分子和DNA损伤产物作为疾病风险评估和干预预测生物标志物的有效性。
