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香芹酚对1,2 - 二甲基肼加葡聚糖硫酸钠诱导的Fischer 344大鼠结肠炎症相关致癌作用具有抗氧化和抗炎作用。

Carvacrol exhibits anti-oxidant and anti-inflammatory effects against 1, 2-dimethyl hydrazine plus dextran sodium sulfate induced inflammation associated carcinogenicity in the colon of Fischer 344 rats.

作者信息

Arigesavan Kaninathan, Sudhandiran Ganapasam

机构信息

Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, Chennai, 600 025, India.

Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, Chennai, 600 025, India.

出版信息

Biochem Biophys Res Commun. 2015 May 29;461(2):314-20. doi: 10.1016/j.bbrc.2015.04.030. Epub 2015 Apr 14.

Abstract

Chronic inflammation is one of the remarkable etiologic factors for various human ailments including cancer. The well known hypothesis is that persistent inflammation in colon can increase the risk of colorectal cancer (CRC). In this study, a pharmacological evaluation of carvacrol, a phenolic monoterpene constituent of essential oils produced from aromatic plant Oreganum vulgarea sp. on colitis associated colon cancer (CACC) induced by 1,2 Dimethylhydrazine (DMH) and dextran sodium sulfate (DSS) in male Fischer 344 rat model was studied. F344 rats were given three subcutaneous injections of DMH (40 mg/kg body wt) in the first week and were given free access to drinking water containing 1% DSS for the next one week followed by 7-14 days of water as three cycles. Carvacrol was administrated before and after tumor induction at a concentration of 50 mg/kg body weight (o.p). Carvacrol treated groups promotes the endogenous antioxidant system and suppress the inflammation in DMH/DSS induced animals. An increased antioxidant status and restoration of histological lesions in the inflamed colonic mucosa was observed in carvacrol treated rats. This effect was confirmed biochemically by reducing free-radical accumulation and suppressing expression of pro-inflammatory mediators. In this study, Carvacrol significantly increased the anti-oxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) glutathione (GSH) levels and reduced lipid peroxides (LPO), myeloperoxidase (MPO) and nitric oxide (NO) as compared to DMH/DSS induced rats. These dramatic changes facilitate the suppression of pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS), and interleukin-1 beta (IL-1β) in CACC induced rats. Taken together, these findings suggest that Carvacrol may play a beneficial role in DMH/DSS induced experimental rat model and serve as an excellent dietary antioxidant as well as anti-inflammatory agent. It may represent novel therapeutic interventions against colon cancer triggered by chronic inflammation.

摘要

慢性炎症是包括癌症在内的各种人类疾病的重要病因之一。著名的假说是结肠中的持续炎症会增加结直肠癌(CRC)的风险。在本研究中,对香芹酚进行了药理学评估,香芹酚是芳香植物牛至(Oreganum vulgarea sp.)产生的精油中的一种酚类单萜成分,研究其对雄性Fischer 344大鼠模型中由1,2 - 二甲基肼(DMH)和葡聚糖硫酸钠(DSS)诱导的结肠炎相关结肠癌(CACC)的作用。F344大鼠在第一周皮下注射三次DMH(40 mg/kg体重),接下来一周自由饮用含1% DSS的饮用水,然后饮用7 - 14天的水,如此循环三个周期。在肿瘤诱导前后以50 mg/kg体重(口服)的浓度给予香芹酚。香芹酚处理组促进内源性抗氧化系统并抑制DMH/DSS诱导动物的炎症。在香芹酚处理的大鼠中观察到抗氧化状态增加以及炎症性结肠黏膜组织学损伤的恢复。通过减少自由基积累和抑制促炎介质的表达,从生化角度证实了这种作用。在本研究中,与DMH/DSS诱导的大鼠相比,香芹酚显著提高了超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽(GSH)等抗氧化酶的水平,并降低了脂质过氧化物(LPO)、髓过氧化物酶(MPO)和一氧化氮(NO)的水平。这些显著变化有助于抑制CACC诱导大鼠中的促炎介质,如诱导型一氧化氮合酶(iNOS)和白细胞介素 - 1β(IL - 1β)。综上所述,这些发现表明香芹酚可能在DMH/DSS诱导的实验大鼠模型中发挥有益作用,并可作为一种出色的膳食抗氧化剂和抗炎剂。它可能代表针对慢性炎症引发的结肠癌的新型治疗干预措施。

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