目的/背景:本研究旨在评估丁丙诺啡对注射丁丙诺啡的母亲哺乳期大鼠幼崽的肝毒性。丁丙诺啡(BUP),一种半合成的阿片类药物,由于其与其他阿片类药物相比具有较高的安全性和有效性,因此越来越多地作为阿片类药物依赖的一线标准维持治疗。许多研究证实了BUP维持治疗成瘾患者的安全性。目的:本研究旨在评估BUP对肝酶活性的影响,氧化参数,哺乳期间暴露于这种药物的母亲所生的幼崽的肝脏组织病理学变化。
方法:将BUP以0.5或0.1mg/kg的剂量皮下给予泌乳大鼠28天。实验结束时,幼崽被麻醉,从他们的心脏获得血液样本用于测量肝酶。然后解剖动物的肝脏以测量氧化应激参数。此外,将肝脏样本固定以进行组织病理学评估.
结果:研究结果表明,哺乳期暴露于0.5和1mg/kgBUP的母亲出生的幼崽的血清肝酶活性(ALT和AST)降低。BUP不能改变丙二醛(MDA),谷胱甘肽(GSH),一氧化氮(NO)水平,动物肝脏组织中的超氧化物歧化酶(SOD)活性。一些黑带的空泡肝细胞,偏心核,坏死与溶核核,有丝分裂图,在接受1mg/kgBUP的幼犬中观察到多个双核细胞。
结论:结论:BUP可能会在哺乳期暴露于该药物的母亲所生的幼崽中引起肝功能障碍。
OBJECTIVE: 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.
OBJECTIVE: 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.
CONCLUSIONS: In conclusion, BUP may induce liver dysfunction in pups born to mothers exposed to this drug during lactation.