评估暴露于丁丙诺啡的母亲在哺乳期所生幼鼠的肝毒性

Q2 Medicine
Babak Roshanravan, Michael Aschner, Hamed Aramjoo, Ali Mohammad Pourbagher-Shahri, Saeed Samarghandian, Tahereh Farkhondeh
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引用次数: 0

摘要

目的:本研究旨在评估丁丙诺啡对注射丁丙诺啡的母鼠哺乳期幼鼠的肝毒性。丁丙诺啡(BUP)是一种半合成阿片类药物,与其他阿片类药物相比,具有较高的安全性和有效性,因此越来越多地被用作阿片类药物依赖的一线标准维持治疗药物。大量研究证实,对成瘾患者进行 BUP 维持治疗是安全的:本研究旨在评估 BUP 对哺乳期暴露于该药物的母亲所生幼崽的肝酶活性、氧化参数和肝组织病理学变化的影响:方法:给哺乳期大鼠皮下注射剂量为 0.5 或 0.1 mg/kg 的 BUP,连续 28 天。实验结束后,对幼鼠进行麻醉,并从其心脏采集血液样本以测定肝酶。然后解剖动物肝脏,测量氧化应激参数。此外,还对肝脏样本进行固定,以进行组织病理学评估:结果:研究结果表明,在哺乳期接触 0.5 和 1 毫克/千克 BUP 的母亲所生幼崽的血清肝酶(谷丙转氨酶和谷草转氨酶)活性降低。BUP 不会改变动物肝组织中的丙二醛 (MDA)、谷胱甘肽 (GSH)、一氧化氮 (NO) 水平和超氧化物歧化酶 (SOD) 活性。接受 1 毫克/千克 BUP 治疗的幼鼠肝脏组织中出现了一些空泡化的肝细胞,细胞核颜色变深、偏心、坏死并伴有溶胶核、有丝分裂图形和多个双核细胞:总之,在哺乳期接触过 BUP 的母亲所生的幼崽可能会出现肝功能异常。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Evaluation of the Hepatotoxicity of Buprenorphine in Rat Pups Born to an Exposed Mother During Lactation.

Aims: This study aimed to evaluate the hepatotoxicity of buprenorphine in lactating rat pups of buprenorphine-injected mothers. Buprenorphine (BUP), a semisynthetic opioid, is increasingly administrated as a first-line standard maintenance treatment for opioid dependence due to its high safety and efficacy compared to other opioids. Numerous studies have confirmed the safety of BUP maintenance treatment in addicted patients.

Objectives: This study was designed to assess the effects of BUP on the activities of liver enzymes, oxidative parameters, and liver histopathological changes in pups born to a mother exposed to this drug during lactation.

Methods: BUP at a dose of 0.5 or 0.1 mg/kg was subcutaneously administrated to lactating rats for 28 days. At the end of the experiment, the pups were anesthetized, and blood samples were obtained from their hearts for measuring liver enzymes. Then the livers of the animals were dissected to measure oxidative stress parameters. In addition, the liver samples were fixed for histopathological evaluation.

Results: The findings indicated a decrease in the activities of serum liver enzymes (ALT and AST) of the pups born to mothers exposed to 0.5 and 1 mg/kg of BUP during lactation. BUP could not change malondialdehyde (MDA), glutathione (GSH), nitric oxide (NO) levels, nor superoxide dismutase (SOD) activity in the liver tissue of animals. Some vacuolated hepatocytes with dark, eccentric nuclei, necrosis with karyolytic nuclei, mitotic figures, and multiple binucleated cells were seen in the pups which received 1 mg/kg of BUP.

Conclusion: In conclusion, BUP may induce liver dysfunction in pups born to mothers exposed to this drug during lactation.

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来源期刊
Cardiovascular and Hematological Agents in Medicinal Chemistry
Cardiovascular and Hematological Agents in Medicinal Chemistry Medicine-Cardiology and Cardiovascular Medicine
CiteScore
2.70
自引率
0.00%
发文量
34
期刊介绍: Cardiovascular & Hematological Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in medicinal chemistry and rational drug design for the discovery of new Cardiovascular & Hematological Agents. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics in Cardiovascular & Hematological medicinal chemistry. Cardiovascular & Hematological Agents in Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in cardiovascular & hematological drug discovery.
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