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褪黑素和二甲双胍抑制苯并(a)芘诱导的小鼠皮肤癌发生

[Melatonin and metformin inhibit skin carcinogenesis induced by benz(a)pyrene in mice].

作者信息

Deriabina O N, Plotnikova N A, Anisimov V N

出版信息

Vopr Onkol. 2010;56(5):583-7.

PMID:21137239
Abstract

One hundred and twenty SHR male mice were randomly divided into 4 groups. Their clean-shaven backs were painted with 0.2 ml of 0.05% acetone solution of benz(a)pyrene (BP) twice a week. Group 1 was in control and received no additional treatment. From beginning to end (6 months), the remaining mice received melatonin 2 mg/l with drinking water at nighttime (group 2), metformin 200 mg/l with drinking water during 24 hrs (group 3), melatonin and metformin as in groups 2 and 3 (group 4). There was a separate group of intact animals. Skin tumor frequency decreased: among melatonin/metformin-treated mice (groups 1-4) - 83.3%, 66.7%, 60%83 and 50%; squamous cell carcinoma - 56.73%, 36.7%, 20% and 20%. Treatment with melatonin and metformin and their combinations was followed by significantly lower tumor multiplicity and smaller size, longer latency period and survival of tumor-bearers. After BP, levels of malonic dialdehyde (MDA) and catalase rose in blood serum while concentrations of the latter in skin tumors were higher than in cutaneous homogenates in intact animals. Melatonin and metformin significantly lowered MDA content of blood serum as compared with group 1. Blood serum catalase fell after their joint administration whereas it was 2.6 times as high in cutaneous homogenates after metformin. However, it decreased after melatonin.

摘要

120只雄性自发性高血压大鼠(SHR)被随机分为4组。每周两次在其剃毛的背部涂抹0.2毫升0.05%的苯并(a)芘(BP)丙酮溶液。第1组为对照组,不接受额外处理。从始至终(6个月),其余小鼠在夜间饮用含2毫克/升褪黑素的水(第2组),在24小时内饮用含200毫克/升二甲双胍的水(第3组),第4组同时饮用含褪黑素和二甲双胍的水,剂量同第2组和第3组。另有一组未处理的完整动物。皮肤肿瘤发生率降低:在接受褪黑素/二甲双胍处理的小鼠中(第1 - 4组)分别为83.3%、66.7%、60%和50%;鳞状细胞癌发生率分别为56.73%、36.7%、20%和20%。褪黑素、二甲双胍及其联合治疗后,肿瘤数量显著减少、肿瘤尺寸变小、潜伏期延长且荷瘤小鼠的生存期延长。涂抹BP后,血清中丙二醛(MDA)水平和过氧化氢酶升高,而皮肤肿瘤中过氧化氢酶的浓度高于未处理动物皮肤匀浆中的浓度。与第1组相比,褪黑素和二甲双胍显著降低了血清中MDA的含量。联合给药后血清过氧化氢酶水平下降,而二甲双胍处理后皮肤匀浆中的过氧化氢酶水平是未处理动物的2.6倍。不过,褪黑素处理后其水平下降。

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