title: Impact of perinatal exposure to acetaminophen on hepatocellular metabolic function in offspring.
abstract: Acetaminophen (APAP), an over the counter (OTC) medication, is widely used in antipyretic treatment. Although the risk of dose-dependent cytotoxicity has been known, the potential effect of perinatal exposure to acetaminophen on metabolic function in offspring remains uninvestigated. Therefore, we established a prenatally APAP-exposed pregnancy mouse model to assess the possible adverse effect on liver metabolic function in offspring. Biochemical assays were applied in analysis of basic metabolic parameters in postnatal mice. Further, immunoblotting assay was used to assess the expressions of insulin receptor β (IRβ), insulin receptor substrate 1 (IRS1), phospho-Akt and phospho-GSK-3β proteins in liver cells. In addition, hepatic glucose transporter 2 (GLUT2) immunoactivity was determined by using immunohistochemistry staining. Compared with untreated postnatal mice, APAP-exposed offspring induced impaired glucose metabolism, increased plasma insulin level, and reduced liver glycogen content. In addition, APAP exposure decreased the expressions of IRS1 and phospho-GSK-3β, phospho-AKT proteins and down-regulated the level of glucose-import regulator GLUT2 in the liver. Taken together, our preliminary findings indicate that perinatal APAP exposure-impaired hepatic glucose metabolism in offspring may be associated with disturbance of insulin-dependent AKT signaling in the liver.
authors.affiliation: Department of Pharmacy, The Second People's Hospital of Nanning City, The Third Affiliated Hospital of Guangxi Medical University Nanning 530031, Guangxi, PR China.
authors.forename: Ka
authors.initials: K
authors.lastname: Wu
authors.affiliation: Department of Pharmacy, Guigang City People's Hospital, The Eighth Affiliated Hospital of Guangxi Medical University Guigang 537100, Guangxi, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: Guo
authors.affiliation: Department of Pharmacy, Guigang City People's Hospital, The Eighth Affiliated Hospital of Guangxi Medical University Guigang 537100, Guangxi, PR China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Lu
authors.affiliation: Guangxi Medical University Guilin 541004, Guangxi, PR China.
authors.forename: Xinmou
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Pharmacy, The Second People's Hospital of Nanning City, The Third Affiliated Hospital of Guangxi Medical University Nanning 530031, Guangxi, PR China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Pan
authors.affiliation: Guilin Medical University Guilin 541004, Guangxi, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Su
keywords: Acetaminophen; glucose metabolism; liver; perinatal exposure