Impact of antidepressant drug clomipramine on hepatorenal functions, lipid peroxidation, micronucleus frequencies and DNA damage using an alkaline comet assay

Abstract

Clomipramine is a tricyclic antidepressant commonly used to treat anxiety related behavioral disorders in human and animals. The current study was performed to assess the effects of different therapeutic doses of clomipramine hydrochloride supplementation on hepato-renal functions, lipid peroxidation, frequencies of micronucleated polychromatic erythrocytes in bone marrow, DNA damage in peripheral blood lymphocytes using the comet assay and effects of withdrawal of the drug for 4 weeks on these parameters. Forty two Swiss albino male mice were divided into seven equal groups. The first group served as a control, while groups 2, 4 and 6 were orally treated with low (75 mg/kg of body weight), medium ((100 mg/kg of body weight), and high doses (250 mg/kg of body weight), respectively of clomipramine hydrochloride daily for 30 days. However, groups 3, 5 and 7 served as low, medium and high withdrawal groups for 4 weeks. Different therapeutic doses of clomipramine hydrochloride resulted in a significant increase in the levels of serum ALT, AST, BUN and creatinine compared to control. Also, plasma malondialdehyde levels showed were significant increase in mice treated by different therapeutic doses of clomipramine hydrochloride compared to control group. In contrast, the administration of clomipramine hydrochloride in three therapeutic doses for 30 days caused a significant increase in the frequency of micronuclei in polychromatic erythrocytes of mice bone marrow, this increase reached more than ten times the value determined before the treatment and directly proportional to the dose. The level of basal endogenous DNA damage measured as the mean of percentage of DNA in the tail of the lymphocytes in mice treated by low, medium and high therapeutic doses of clomipramine hydrochloride were significantly higher than in controls. However, in the recovery period (4weeks), a significant amelioration in all studied parameters was observed. Results indicated that, clomipramine is a hepato renal toxic drug and induces a significant amount of DNA damage and in-vivo genotoxic drug.