雄性小鼠从青春期前到成年期暴露于洛伐他汀的肝组织病理学和形态计量学变化:一种可能的适应性肝反应。

IF 2.1 4区 医学 Q3 CHEMISTRY, MULTIDISCIPLINARY
Drug and Chemical Toxicology Pub Date : 2025-05-01 Epub Date: 2024-08-08 DOI:10.1080/01480545.2024.2385609
Jennyfer Karen Knorst, Tainara Fernandes de Mello, Amanda Rebonatto Oltramari, Alice Santos da Silva, Gabriel Adan Araújo Leite
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引用次数: 0

摘要

不良饮食习惯和减少体育锻炼等生活方式的改变损害了人体的血脂状况。他汀类药物被广泛用于治疗血脂异常,其中罗伐他汀对血脂的改善更大,可从小开始使用。本研究旨在评估雄性小鼠从出生后第 23 天起至出生后第 80 天,每天服用 0.9% 生理盐水或 1.5 或 5.5 mg/kg 剂量的罗伐他汀对肝脏的影响。在治疗过程中,对小鼠的体重增加、饮水量和食物消耗量进行监测。小鼠在出生后第 80 天被安乐死,同时采集血液以获得血清,并收集和称重多个器官。血清用于评估脂质概况和肝损伤标志物。对肝脏的组织病理学、形态计量学和立体学变化进行评估。罗伐他汀暴露组的体重增加、水和食物消耗量暂时减少。洛伐他汀治疗组和对照组的总胆固醇水平都有所下降,并显示出肝脏组织对长期暴露的适应迹象,如肝窦扩张、炎症浸润和肝细胞死亡。这些结果被认为是治疗的副作用,可能表明肝脏适应了长期暴露。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Hepatic histopathological and morphometric changes in male mice exposed to rosuvastatin from pre-puberty to adulthood: a possible adaptive hepatic response.

Lifestyle changes, such as poor eating habits and a reduction in physical exercise, have impaired human lipid profiles. Statins are widely used to treat dyslipidemias, of which rosuvastatin shows greater improvement in the lipid profile and may be used since childhood. This study aimed to assess the hepatic effects when male mice were given 0.9% saline solution or doses of rosuvastatin of 1.5 or 5.5 mg/kg/day from postnatal day (PND) 23 until PND 80. Body mass gain and water and food consumption were monitored during the treatment. Mice were euthanized on PND 80 when blood was collected for serum obtainment, and several organs were collected and weighed. Serum was used for evaluating lipid profiles and markers of hepatic injuries. The liver was assessed for histopathological, morphometric, and stereological changes. There was a temporary reduction in body mass gain and water and food consumption in the rosuvastatin-exposed groups. Both rosuvastatin-treated groups exhibited reduced total cholesterol levels and showed signs of hepatic tissue adaptation in response to prolonged exposure, such as sinusoidal dilation, inflammatory infiltrates, and cell death of hepatocytes. These results are considered side effects of the treatment and may indicate a hepatic adaptation to the chronic exposure.

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来源期刊
Drug and Chemical Toxicology
Drug and Chemical Toxicology 医学-毒理学
CiteScore
6.00
自引率
3.80%
发文量
99
审稿时长
3 months
期刊介绍: Drug and Chemical Toxicology publishes full-length research papers, review articles and short communications that encompass a broad spectrum of toxicological data surrounding risk assessment and harmful exposure. Manuscripts are considered according to their relevance to the journal. Topics include both descriptive and mechanics research that illustrates the risk assessment implications of exposure to toxic agents. Examples of suitable topics include toxicological studies, which are structural examinations on the effects of dose, metabolism, and statistical or mechanism-based approaches to risk assessment. New findings and methods, along with safety evaluations, are also acceptable. Special issues may be reserved to publish symposium summaries, reviews in toxicology, and overviews of the practical interpretation and application of toxicological data.
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