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桑色素对瑞士白化小鼠全身γ射线照射的抗致断裂活性。

Anticlastogenic activity of morin against whole body gamma irradiation in Swiss albino mice.

作者信息

Parihar Vipan Kumar, Prabhakar Koiram Rajanna, Veerapur Veeresh Prabhakar, Priyadarsini Kavirayani Indira, Unnikrishnan Mazhuvancherry Kesavan, Rao Chamallamudi Mallikajuna

机构信息

Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal-576104, Karnataka, India.

出版信息

Eur J Pharmacol. 2007 Feb 14;557(1):58-65. doi: 10.1016/j.ejphar.2006.09.073. Epub 2006 Oct 19.

Abstract

Anticlastogenic activity of morin was explored against whole body gamma radiation, at a dose rate of 1.66 Gy/min in Swiss albino mice pretreated intraperitoneal or orally. Pretreatment with morin 10, 25, 50, 75, 100, 125, and 150 mg/kg, i.p. delayed and reduced percentage mortality and increased mean survival times in mice irradiated with 10 Gy gamma radiation. Intraperitoneal route was found superior to oral route. An i.p. dose of 100 mg/kg was found to be the most effective dose in preventing radiation-induced weight loss, increasing the mean survival times and reducing percentage mortality. Morin (100 mg/kg) pretreatment effectively maintained spleen index (spleen weight/body weight x 100) and stimulated endogenous spleen colony forming units. Pretreatment with morin (100 mg/kg) significantly reduced dead, inflammatory, and mitotic cells in irradiated mice jejunum along with a significant increase in goblet cells and rapidly multiplying crypt cells. Morin (100 mg/kg) also maintained the villus height close to normal, prevented mucosal erosion and basement membrane damage in irradiated jejunum. Nuclear enlargement in epithelial cells of jejunum was lower in morin treated mice compared to radiation control. Morin (100 mg/kg) also significantly elevated the endogenous antioxidant enzymes viz. glutathione S transferase (GST), superoxide dismutase (SOD) and reduced glutathione (GSH), in normal mice at 2, 4 and 8 h post treatment. Drastic decrease in endogenous enzymes (GSH, GST, catalase and SOD) and total thiols was observed in irradiated mice at 2, 4 and 8 h post irradiation, while pretreatment with morin (100 mg/kg) prevented this decrease. Morin (100 mg/kg) also elevated radiation LD(50) from 9.2 to 10.1 Gy, indicating a dose modifying factor (DMF) of 1.11.

摘要

在经腹腔或口服预处理的瑞士白化小鼠中,以1.66 Gy/分钟的剂量率,研究了桑色素对全身γ辐射的抗致突变活性。用10、25、50、75、100、125和150 mg/kg的桑色素腹腔注射预处理,可延迟和降低10 Gy γ辐射小鼠的死亡率,并延长平均存活时间。发现腹腔给药途径优于口服途径。腹腔注射100 mg/kg的剂量被认为是预防辐射引起的体重减轻、延长平均存活时间和降低死亡率的最有效剂量。桑色素(100 mg/kg)预处理有效地维持了脾脏指数(脾脏重量/体重×100),并刺激了内源性脾集落形成单位。桑色素(100 mg/kg)预处理显著减少了受辐射小鼠空肠中的死亡、炎症和有丝分裂细胞,同时杯状细胞和快速增殖的隐窝细胞显著增加。桑色素(100 mg/kg)还使绒毛高度维持在接近正常水平,防止受辐射空肠的粘膜糜烂和基底膜损伤。与辐射对照组相比,桑色素处理的小鼠空肠上皮细胞核增大程度较低。桑色素(100 mg/kg)还显著提高了正常小鼠在处理后2、4和8小时的内源性抗氧化酶,即谷胱甘肽S转移酶(GST)、超氧化物歧化酶(SOD)和还原型谷胱甘肽(GSH)。在辐射后2、4和8小时,受辐射小鼠的内源性酶(GSH、GST、过氧化氢酶和SOD)和总硫醇急剧下降,而桑色素(100 mg/kg)预处理可防止这种下降。桑色素(100 mg/kg)还将辐射LD(50)从9.2 Gy提高到10.1 Gy,表明剂量修正因子(DMF)为1.11。

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