Cardiac and hepatic side effects of fluoxetine in male and female adolescent rats

Background

Fluoxetine (FLX) is widely prescribed as an antidepressant medicine in the juvenile population.

Objectives

Although some adverse effects of FLX have been reported in adults, the present study aimed to investigate the side effects of FLX treatment during adolescence on the cardiac and hepatic systems.

Methods

Male and female rats were gavaged with FLX (5 mg/kg/day) on postnatal days (PND) 21 to PND 60. Following treatment, blood samples were collected and hepatic enzymes were evaluated. The specimens of the liver and heart of animals were subjected to histopathological assessment.

Results

Fluoxetine significantly raised serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in males, whereas the aspartate aminotransferase (AST) level increased in both male and female animals. In the histopathological study, hepatic plates were more seriously affected, and the sinusoids were irregular in adolescent male rats. Degenerative changes were observed especially in the first and second hepatic zones of FLX-treated male rats. Signs of inflammation and accumulation of lymphoid groups were frequently observed in the portal triad of the hepatic lobules. These alterations were more severe in male livers. Minimum or nearly normal changes were observed in female liver slides. In addition, the histological assessment indicated that treatment with FLX during adolescence also increased the heart's weight and the wall thickness of the right and left ventricles (hypertrophy) in male and especially female animals.

Conclusion

Our findings may provide new insights into the cardiac and hepatic adverse effects of FLX.