Alleviation of the hepatotoxicity effects of fluoxetine using acetylcysteine with the royal jelly in rats

Background Fluoxetine is commonly used as the initial option for depressive symptoms and other neurological disorders. The repeated use of fluoxetine was related to hepatotoxicity and persistent liver disease. N-acetylcysteine (NAC) and royal jelly, a natural substance, possess hepatoprotective activity. Objective Compare the hepatoprotective activity of N-acetylcysteine and royal jelly against fluoxetine hepatotoxicity in rats. Materials and methods Rats were being randomized to five groups and orally administered every day for 28 days: Control group (0.2 ml of distilled water), fluoxetine group (10 mg/kg), royal jelly (150 mg/kg) + fluoxetine (10 mg/kg) group, NAC (200 mg/kg) + fluoxetine (10 mg/kg) group, and royal jelly (150 mg/kg) + NAC (200 mg/kg) + fluoxetine (10 mg/kg) group. The time between doses was 60 min. After 28-day treatment, the rats were sacrificed after 24 h last dose; blood and liver tissue were collected for the enzymatic and oxidative stress evaluation by ELISA and histological analysis. Results Fluoxetine-induced hepatotoxicity was demonstrated by a significant change ( p < 0.05) in the liver enzyme activity and produced hepatic histological abnormalities in tissue compared to the normal control group, while the other groups, N-acetylcysteine, royal jelly, and combination of N-acetylcysteine and royal jelly, all exhibited a significant ( p > 0.05) reduction in ALT serum level in contrast to fluoxetine group. Conclusion Royal jelly and N-acetylcysteine are protective against rat hepatotoxicity caused by fluoxetine. This result might result from decreased inflammation.