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急性黄曲霉毒素 B 诱导的胃十二指肠和肝氧化损伤伴随着大鼠时间依赖性高乳酸血症。

Acute aflatoxin B-induced gastro-duodenal and hepatic oxidative damage is preceded by time-dependent hyperlactatemia in rats.

机构信息

Departvment of Veterinary Physiology and Biochemistry, Faculty of Veterinary Medicine, University of Ibadan, Ibadan, Nigeria.

Department of Veterinary Surgery and Radiology, University of Ibadan, Ibadan, Nigeria.

出版信息

Mycotoxin Res. 2020 Nov;36(4):443-452. doi: 10.1007/s12550-020-00408-6. Epub 2020 Sep 21.

DOI:10.1007/s12550-020-00408-6
PMID:32954470
Abstract

Elevated serum lactate concentration has been used to predict the risk of fatality in various disease states in acutely ill patients or poisoning with different chemicals. However, its utility in predicting disease progression during acute aflatoxicosis has not been investigated. This study was designed to evaluate changes in blood lactate levels following acute exposure to aflatoxin B (AFB) and to determine whether changes in blood lactate levels bear any relationship with biochemical and/or morphological lesions in the stomach, duodenum, and liver. Twenty-one male Wistar rats were randomly divided into three groups (n = 7 rats /group) including Group A (control) receiving vehicle alone and Groups B and C treated with single oral doses of AFB at 2.5 and 5 mg/kg, respectively. AFB produced significant (p < 0.05) time- and dose-dependent increase in blood lactate concentration as early as 1 h following its administration, with further increases observed at 3 h and 6 h. The hyperlactatemia accompanied tissue oxidative changes including increased HO and MDA, as well as depletion in glutathione, glutathione peroxidase, superoxide dismutase, and total thiols in gastro-duodenal and hepatic tissues. The oxidative changes were reflected in morphological alterations observed at histopathology with more severe lesions observed with the higher dose of AFB. Serum levels of pro-inflammatory cytokines (TNF-α and IL-1β) were, however, differently modified by AFB administration. Taken together, the results from this study gives indication that hyperlactatemia may find utility in predicting the severity of tissue damage induced by acute AFB exposure.

摘要

血清乳酸浓度升高已被用于预测各种疾病状态下急性病患者或不同化学物质中毒的死亡风险。然而,其在预测急性黄曲霉毒素中毒期间疾病进展的用途尚未得到研究。本研究旨在评估急性接触黄曲霉毒素 B (AFB) 后血液乳酸水平的变化,并确定血液乳酸水平的变化是否与胃、十二指肠和肝脏的生化和/或形态损伤有关。21 只雄性 Wistar 大鼠被随机分为三组(n = 7 只/组),包括 A 组(对照组)单独接受载体,B 组和 C 组分别接受 2.5 和 5 mg/kg 的 AFB 单次口服剂量。AFB 给药后 1 小时即可引起血乳酸浓度显著(p < 0.05)、时间和剂量依赖性增加,3 小时和 6 小时后进一步增加。高乳酸血症伴有组织氧化变化,包括 HO 和 MDA 增加,以及胃十二指肠和肝组织中谷胱甘肽、谷胱甘肽过氧化物酶、超氧化物歧化酶和总巯基的耗竭。氧化变化反映在组织病理学观察到的形态改变中,较高剂量的 AFB 观察到更严重的病变。然而,血清促炎细胞因子(TNF-α 和 IL-1β)的水平被 AFB 给药不同地修饰。综上所述,这项研究的结果表明,高乳酸血症可能有助于预测急性 AFB 暴露引起的组织损伤的严重程度。

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