Evaluation of the hepatotoxicity of buprenorphine in rat pups born to an exposed mother during lactation

Cardiovasc Hematol Agents Med Chem. 2023 May 25. doi: 10.2174/1871525721666230525152026. Online ahead of print.

Abstract

Aim/ Background: 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.

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

Keywords: Buprenorphine; lactation; liver; oxidative stress parameters; pup; rat.