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香茅醇对 DMBA 诱导的大鼠乳腺癌的剂量依赖性化学预防作用。

Dose-dependent chemopreventive effects of citronellol in DMBA-induced breast cancer among rats.

机构信息

Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, Tamil Nadu, India.

出版信息

Drug Dev Res. 2019 Sep;80(6):867-876. doi: 10.1002/ddr.21570. Epub 2019 Jul 16.

Abstract

Breast cancer is one of the most common cancers among women world wide and its incidence is on tremendous increase. The present study is aimed to analyze the dose-dependent chemopreventive efficacy of citronellol on 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary carcinogenesis. The mammary tumor was induced through a single dose of DMBA (25 mg/rat) injected subcutaneously near the mammary gland of rats. In DMBA-injected rats, 100% tumor incidence, increased tumor volume, and tumor burden along with loss of body weight were observed. Biochemical analysis revealed the increased levels of phase I detoxification proteins (cytochrome P450 and b5) and decreased activities of phase II detoxification enzymes (glutathione-S-transferase and glutathione reductase) in hepatic and mammary tissues. The levels of enzymatic and non-enzymatic antioxidants (superoxidedismutase, catalase, glutathione peroxidase, and (GPx) and reduced glutathione) were decreased and lipid peroxidation by-products (thiobarbituric acid reactive substance and lipid hydroperoxide) got increased in plasma and mammary tissues. Oral administration of different doses of citronellol (25, 50, and 100 mg/kg body weight) to DMBA-treated rats for 16 weeks absolutely inhibited the tumor incidence and restored the biochemical parameters near to normal level in 50 and 100 mg doses whereas the histopathological studies also supported the biochemical findings. Hence, the result suggests that the citronellol of 50 mg/kg body weight exerted significant chemopreventive effects and can be considered as a minimum optimum dose in the prevention of mammary carcinogenesis.

摘要

乳腺癌是全球女性最常见的癌症之一,其发病率正在急剧上升。本研究旨在分析香茅醇对 7,12-二甲基苯并(a)蒽(DMBA)诱导的大鼠乳腺肿瘤发生的剂量依赖性化学预防作用。通过在乳腺附近皮下注射 DMBA(25mg/大鼠)单次剂量诱导乳腺肿瘤。在 DMBA 注射大鼠中,观察到 100%的肿瘤发生率、肿瘤体积增加、肿瘤负荷以及体重减轻。生化分析显示肝和乳腺组织中 I 相解毒蛋白(细胞色素 P450 和 b5)水平升高,II 相解毒酶(谷胱甘肽-S-转移酶和谷胱甘肽还原酶)活性降低。血浆和乳腺组织中酶和非酶抗氧化剂(超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶和(GPx)和还原型谷胱甘肽)水平降低,丙二醛(TBARS)和脂质过氧化物的产物增加。香茅醇(25、50 和 100mg/kg 体重)以不同剂量口服给予 DMBA 处理的大鼠 16 周,完全抑制肿瘤发生率,并使生化参数在 50 和 100mg 剂量下接近正常水平,而组织病理学研究也支持生化发现。因此,结果表明香茅醇 50mg/kg 体重的剂量表现出显著的化学预防作用,可被认为是预防乳腺肿瘤发生的最小最佳剂量。

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