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法呢醇可减轻 1,2-二甲基肼诱导的 Wistar 大鼠结肠氧化应激、炎症和凋亡反应。

Farnesol attenuates 1,2-dimethylhydrazine induced oxidative stress, inflammation and apoptotic responses in the colon of Wistar rats.

机构信息

Molecular Carcinogenesis and Chemoprevention Division, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi, India.

出版信息

Chem Biol Interact. 2011 Jul 15;192(3):193-200. doi: 10.1016/j.cbi.2011.03.009. Epub 2011 Mar 29.

Abstract

Colon cancer is the major health hazard related with high mortality and it is a pathological consequence of persistent oxidative stress and inflammation. Farnesol, an isoprenoid alcohol, has been shown to possess antioxidant, anti-inflammatory and chemopreventive properties. The present study was performed to evaluate the protective efficacy of farnesol against 1,2-dimethylhydrazine (DMH) induced oxidative stress, inflammatory response and apoptotic tissue damage. Farnesol was administered once daily for seven consecutive days at the doses of 50 and 100 mg/kg body weight in corn oil. On day 7, a single injection of DMH was given subcutaneously in the groin at the dose of 40 mg/kg body weight. Protective effects of farnesol were assessed by using caspase-3 activity, tissue lipid peroxidation (LPO) and antioxidant status as end point markers. Further strengthening was evident on histopathological observations used to assess the protective efficacy of farnesol. Prophylactic treatment with farnesol significantly ameliorates DMH induced oxidative damage by diminishing the tissue LPO accompanied by increase in enzymatic viz., superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST) and quinone reductase (QR) and non-enzymatic viz., reduced glutathione (GSH) antioxidant status. Farnesol supplementation significantly decreased caspase-3 activity in colonic tissue. Histological findings also revealed that pretreatment with farnesol significantly reduced the severity of submucosal edema, regional destruction of the mucosal layer and intense infiltration of the inflammatory cells in mucosal and submucosal layers of the colon. The data of the present study suggest that farnesol effectively suppress DMH induced colonic mucosal damage by ameliorating oxidative stress, inflammatory and apoptotic responses.

摘要

结肠癌是与高死亡率相关的主要健康危害,是持续氧化应激和炎症的病理后果。法呢醇,一种异戊二烯醇,已被证明具有抗氧化、抗炎和化学预防特性。本研究旨在评估法呢醇对 1,2-二甲基肼 (DMH) 诱导的氧化应激、炎症反应和凋亡组织损伤的保护作用。法呢醇在玉米油中每天连续给药 7 天,剂量为 50 和 100mg/kg 体重。第 7 天,在腹股沟皮下单次注射 40mg/kg 体重的 DMH。使用 caspase-3 活性、组织脂质过氧化 (LPO) 和抗氧化状态作为终点标志物来评估法呢醇的保护作用。进一步的组织病理学观察加强了法呢醇的保护效果评估。法呢醇的预防性治疗通过减少组织 LPO 显著改善了 DMH 诱导的氧化损伤,同时增加了酶如超氧化物歧化酶 (SOD)、过氧化氢酶、谷胱甘肽过氧化物酶 (GPx)、谷胱甘肽还原酶 (GR)、谷胱甘肽-S-转移酶 (GST) 和醌还原酶 (QR) 和非酶如还原型谷胱甘肽 (GSH) 的抗氧化状态。法呢醇补充剂显著降低了结肠组织中的 caspase-3 活性。组织学发现还表明,法呢醇预处理显著减轻了黏膜下层水肿、黏膜层区域性破坏和黏膜和黏膜下层炎症细胞的强烈浸润的严重程度。本研究的数据表明,法呢醇通过改善氧化应激、炎症和凋亡反应,有效地抑制 DMH 诱导的结肠黏膜损伤。

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