Citalopram Induced Cardiotoxicity in Rats at Repeated Doses
Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Anadolu University, 1Department of Biology, Faculty of Science, Eskisehir Technical University, Eskisehir 26470, Turkey
Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Anadolu University, 1Department of Biology, Faculty of Science, Eskisehir Technical University,
Although the correlation between citalopram and cardiovascular pathologies was realized via case studies, there is no experimental study that was performed independently of other risk factors related to cardiotoxicity. In the study reported here, we aimed to identify the cardiotoxic effects of citalopram by evaluating serum cardiac biomarkers, such as serum aspartate transaminase, creatine kinase-myoglobin binding, lactate dehydrogenase and troponin-T levels as well as electrocardiogram parameters, deoxyribonucleic acid damage in cardiomyocytes and histological findings of heart tissue in rats that were administered oral doses of 5, 10, or 20 mg/kg of citalopram for 28 d. Additionally, to investigate possible mechanisms underlying cardiotoxicity, glutathione and malondialdehyde levels in cardiac tissue were determined to evaluate oxidative stress. According to our results, heart rates were increased, PR intervals were prolonged, and T wave amplitudes were significantly decreased in the 20 mg/kg citalopram-administered groups when compared with the control group. Additionally, serum aspartate transaminase, lactate dehydrogenase and troponin-T levels were significantly increased in the 10 and 20 mg/kg citalopram-administered group compared to the control group. Significant deoxyribonucleic acid damages were observed in the 10 and 20 mg/kg citalopram-administered groups. Histopathological investigations revealed degenerative changes in the 10 and 20 mg/kg citalopram-administered groups. In heart tissues, glutathione levels were decreased in the 10 and 20 mg/kg citalopram-administered groups significantly when compared with the control group. These findings indicated the relationship between high-dose and subtherapeutic-dose citalopram administration and cardiac morphological, biochemical and functional toxic effects.