Volume 16, Issue 38, July - December, 2022

Effect of the antidepressant drug dapoxetine on acute liver injury caused by carbon tetrachloride in the rat

Omar ME Abdel-Salam^1♦, Eman R Youness², Fatma A Morsy³, Amany A Sleem⁴

¹Department of Toxicology and Narcotics, Medical Research and Clinical Studies Institute, National Research Centre, Cairo, Egypt
²Department of Medical Biochemistry, Medical Research and Clinical Studies Institute, National Research Centre, Cairo, Egypt
³Department of Pathology, Medical Research and Clinical Studies Institute, National Research Centre, Cairo, Egypt
⁴Department of Pharmacology, Medical Research and Clinical Studies Institute, National Research Centre, Cairo, Egypt

^♦Corresponding author
Department of Toxicology and Narcotics, Medical Research and Clinical Studies Institute, National Research Centre, Cairo, Egypt

ABSTRACT

We examined the effect of dapoxetine, a selective serotonin-reuptake inhibitor used in treatment of premature ejaculation in the carbon tetrachloride (CCl4) model of acute liver injury. Dapoxetine (5.4, 10.2 or 21.4 mg/kg) was given once daily orally simultaneously with CCl4 and for 2 consecutive days thereafter. We measured serum aminotransferases activities, liver lipid peroxidation (malondialdehyde: MDA), nitric oxide and reduced glutathione (GSH) concentrations, serum MDA, nitric oxide, serum and liver paraoxonase1 (PON-1) activities and liver Na+ /K+ -ATPase activity. Hepatic histopathology was also done. Results: Rats treated with CCl4 exhibited significantly raised serum aspartate aminotransferase and alanine aminotransferase activities. There were also increased MDA and nitric oxide concentrations in liver and serum whereas liver GSH concentrations, liver and serum PON-1 activities as well as liver Na+ /K+ -ATPase activity were depressed compared with the vehicle group. The administration of dapoxetine to CCl4-treated rats attenuated liver injury, as indicated by the decrease in serum liver enzymes and markers of oxidative stress. The histopathological change induced by CCl4 such as centrilobular necrosis, vacuolar and fatty degeneration, distorted architecture was also improved by dapoxetine in a dose-dependent manner. Thus, in acute liver injury caused by CCl4, the concurrent administration of the antidepressant drug dapoxetine was associated with decreasing oxidative stress and less extent of liver tissue damage

Keywords: dapoxetine, antidepressants, carbon tetrachloride, liver injury, oxidative stress, paraoxonase, Na+ /K+ -ATPase

Drug Discovery, 2022, 16(38), 76-85

PDF