Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran.
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Forchheimer, 209 1300, Morris Park Avenue, Bronx, NY, USA.
Cardiovasc Hematol Agents Med Chem. 2024;22(2):131-138. doi: 10.2174/1871525721666230525152026.
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.
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.
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.
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.
In conclusion, BUP may induce liver dysfunction in pups born to mothers exposed to this drug during lactation.
本研究旨在评估美沙酮在接受美沙酮注射的哺乳期大鼠幼崽中的肝毒性。美沙酮（BUP）是一种半合成阿片类药物，与其他阿片类药物相比，其安全性和疗效更高，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。许多研究已经证实了 BUP 维持治疗在成瘾患者中的安全性。
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。
BUP 以 0.5 或 0.1mg/kg 的剂量皮下注射给哺乳期大鼠 28 天。实验结束时，将幼崽麻醉，从心脏取血样以测量肝酶。然后解剖动物的肝脏以测量氧化应激参数。此外，还固定了肝组织样本进行组织病理学评估。
研究结果表明，哺乳期暴露于 0.5 和 1mg/kg BUP 的母亲所生幼崽的血清肝酶（ALT 和 AST）活性降低。BUP 不能改变丙二醛（MDA）、谷胱甘肽（GSH）、一氧化氮（NO）水平，也不能改变动物肝组织中超氧化物歧化酶（SOD）的活性。接受 1mg/kg BUP 的幼崽可见一些有空泡的肝细胞，细胞核深染、偏心，有核溶解坏死、有丝分裂和多个双核细胞。
总之，哺乳期暴露于 BUP 的母亲所生幼崽可能会出现肝功能障碍。
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