The effect of antidepressant drugs on thioacetamide-induced oxidative stress

O.M.E. Abdel Salam, N.A. Mohammed, A.A. Sleem, A.R. Farrag

Departments of Toxicology and Narcotics, Medical Biochemistry, Pharmacology, and Pathology; National Research Centre, Cairo, Egypt. omasalam@hotmail.com

 

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• Pharmacology

OBJECTIVE: The aim of the present study was to investigate the effect of the serotonin selective reuptake inhibitors (SSRIs) fluoxetine and sertraline and the tricyclic drug imipramine on oxidative stress in the brain and liver caused by thioacetamide in rats.

MATERIALS AND METHODS: Drugs were administered orally once daily at doses of 10 and 20 mg/kg for two weeks prior to intraperitoneal injection of thioacetamide (300 mg/kg). Rats were euthanized 24 h after thioacetamide. Reduced glutathione (GSH), malondialdehyde (MDA) and nitric oxide were measured in brain and liver. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were measured in serum and histopathological evaluation of liver injury was performed.

RESULTS: The administration of thioacetamide increased MDA by 151.8% and 161.2%, increased nitric oxide by 57.2% and 63.9% and decreased GSH by –40.6% and –67% in the brain and liver, respectively. Thioacetamide markedly increased serum ALT, AST and ALP by 277.8, 80.8 and 121%, respectively. In the brain, MDA was decreased in rats treated with fluoxetine or sertraline. The level of GSH increased by fluoxetine and by the higher dose of sertraline. Nitric oxide in brain was unchanged by fluoxetine, but increased after sertraline at 20 mg/kg. Brain MDA was increased by imipramine, which also decreased brain nitrite level. In the liver, fluoxetine or sertraline treatment increased GSH and nitrite levels. MDA was also increased by either drug. The drugs markedly decreased ALT, but increased ALP in serum. Meanwhile, imipramine decreased liver nitric oxide levels (at the lower dose only –32.9%), markedly increased hepatic GSH, but did not change MDA level. Serum ALT decreased by imipramine (but AST and ALP showed no change). Histopathological and histochemical examinations indicated that thioacetamide-induced liver injury was not decreased after treatment with the antidepressant drugs.

CONCLUSIONS: In thioacetamide-treated rats, pretreatment with the SSRIs drugs fluoxetine and sertraline is associated with decreased lipid peroxidation in brain; liver peroxidation, however, is increased. Imipramine displayed opposite effects. The thioacetamide-induced hepatic damage was not reduced by fluoxetine, sertraline or imipramine.

 

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