Abstract
Imipramine is a tricyclic antidepressant that has been approved for treating depression and anxiety in patients and animals and that has relatively mild side effects. However, the mechanisms of imipramine-associated disruption to metabolism and negative hepatic, renal, and retinal effects are not well defined. In this study, we evaluated C57BL6/J mice subjected to a high-fat diet (HFD) to study imipramine’s influences on obesity, fatty liver scores, glucose homeostasis, hepatic damage, distribution of chromium, and retinal/renal impairments. Obese mice receiving imipramine treatment had higher body, epididymal fat pad, and liver weights; higher serum triglyceride, aspartate and alanine aminotransferase, creatinine, blood urea nitrogen, renal antioxidant enzyme, and hepatic triglyceride levels; higher daily food efficiency; and higher expression levels of a marker of fatty acid regulation in the liver compared with the controls also fed an HFD. Furthermore, the obese mice that received imipramine treatment exhibited insulin resistance, worse glucose intolerance, decreased glucose transporter 4 expression and Akt phosphorylation levels, and increased chromium loss through urine. In addition, the treatment group exhibited considerably greater liver damage and higher fatty liver scores, paralleling the increases in patatin-like phospholipid domain containing protein 3 and the mRNA levels of sterol regulatory element-binding protein 1 and fatty acid-binding protein 4. Retinal injury worsened in imipramine-treated mice; decreases in retinal cell layer organization and retinal thickness and increases in nuclear factor κB and inducible nitric oxide synthase levels were observed. We conclude that administration of imipramine may result in the exacerbation of nonalcoholic fatty liver disease, diabetes, diabetic retinopathy, and kidney injury.
Highlights
Imipramine, derived from dibenzazepine, is a prototypical tricyclic antidepressant (TCA)
Weekly food consumption was 21% higher in mice after they were administered imipramine, and their increase was parallel with the food consumption increase in controls (Figure 1b)
We suggest that the increases in body fat as well as retroperitoneal WAT (RWAT), epididymal white adipose tissue (EWAT), and liver weights in the imipramine group may have been caused by increases in adipocyte size and fatty liver scores
Summary
Imipramine, derived from dibenzazepine, is a prototypical tricyclic antidepressant (TCA). Off-label uses include the (1) treatment of panic disorders without or with agoraphobia, (2) second-line treatment of attention deficit hyperactivity disorder in young people, (3) management of bulimia, (4) treatment of postacute and posttraumatic stress, and (5) short-term treatment of acute depression in patients with schizophrenia and bipolar disorder [9,10,11,12]. Side effects such as drowsiness, dry mouth, excitement, and weight or appetite alterations may be induced by imipramine [13]. In-depth explorations of the side effects of imipramine have been inconclusive
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
