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余甘子对小鼠体内苯并[a]芘和环磷酰胺致断裂性的抑制作用。

Inhibitory effect of Emblica officinalis on the in vivo clastogenicity of benzo[a]pyrene and cyclophosphamide in mice.

作者信息

Sharma N, Trikha P, Athar M, Raisuddin S

机构信息

Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.

出版信息

Hum Exp Toxicol. 2000 Jun;19(6):377-84. doi: 10.1191/096032700678815945.

Abstract

Benzo[a]pyrene (B[a]P) and cyclophosphamide (CP) are potent carcinogens/mutagens. Effect of Emblica officinalis extract administration on the in vivo genotoxicity of B[a]P and CP was studied using bone marrow chromosomal aberration and micronucleus induction tests in mice. Three doses (50, 250 and 500 mg/kg body weight) of the plant extract were administered orally for 7 consecutive days prior to the administration of single dose of mutagens (B[a]P 125 mg/kg oral; CP 40 mg/kg i.p.). It was found that administration of 250 and 500 mg/kg of E. officinalis extract significantly inhibited the genotoxicity of B[a]P as well as CP in both the assay systems. Administration of 50 mg/kg of the plant extract had no inhibitory effect. Vitamin C, a major constituent of E. officinalis when administered at dose level of 9 mg/kg b.w. (the approximate estimated amount present in the highest dose of plant extract, i.e. 500 mg) for 7 days did inhibit chromosomal aberrations and micronuclei induction, but not in a significant manner. Effect of administration of the abovementioned effective doses (250 and 500 mg/kg oral for 7 days) of plant extract and vitamin C (9 mg/kg oral for 7 days) on the hepatic activation and detoxification enzymes was also studied. Significant induction in the levels of glutathione content (GSH) and of antioxidant and detoxification enzymes viz., glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S transferase (GST) resulted from plant extract treatment to animals. On the other hand, cytochrome P 450 level was significantly decreased in the plant-extract-treated animals. There was no significant change in cytochrome P 450, GSH contents and activities of enzymes on treatment with vitamin C. The data indicate that the possible mechanism of inhibition by plant extract is mediated by its modulatory effect on hepatic activation and disposition processes.

摘要

苯并[a]芘(B[a]P)和环磷酰胺(CP)是强效致癌物/诱变剂。利用小鼠骨髓染色体畸变和微核诱导试验,研究了余甘子提取物给药对B[a]P和CP体内遗传毒性的影响。在单次给予诱变剂(口服B[a]P 125 mg/kg;腹腔注射CP 40 mg/kg)之前,连续7天口服给予三种剂量(50、250和500 mg/kg体重)的植物提取物。结果发现,在两种检测系统中,给予250和500 mg/kg的余甘子提取物均能显著抑制B[a]P和CP的遗传毒性。给予50 mg/kg的植物提取物没有抑制作用。余甘子的主要成分维生素C,以9 mg/kg体重的剂量水平(最高剂量植物提取物中存在的近似估计量,即500 mg)给药7天,确实能抑制染色体畸变和微核诱导,但效果不显著。还研究了上述有效剂量(口服250和500 mg/kg,共7天)的植物提取物和维生素C(口服9 mg/kg,共7天)对肝脏激活和解毒酶的影响。植物提取物处理动物后,谷胱甘肽含量(GSH)以及抗氧化和解毒酶即谷胱甘肽过氧化物酶(GPx)、谷胱甘肽还原酶(GR)和谷胱甘肽-S转移酶(GST)的水平显著升高。另一方面,植物提取物处理的动物中细胞色素P 4(50)水平显著降低。维生素C处理后,细胞色素P 4(50)、GSH含量和酶活性没有显著变化。数据表明,植物提取物抑制作用的可能机制是通过其对肝脏激活和代谢过程的调节作用介导的。

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