1. Dose-Dependent Subacute Cardiovascular Effects Of Modafinil In Rats
- Author
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Dilan Canyurt, Onural Ozhan, Azibe Yildiz, Seyma Yasar, Nigar Vardi, Ahmet Acet, Hakan Parlakpinar, Yilmaz Cigremis, Mehmet Cansel, Yücel Karaca, and Lokman Hekim Tanriverdi
- Subjects
Health, Toxicology and Mutagenesis ,Dose dependence ,Modafinil ,010501 environmental sciences ,Pharmacology ,Toxicology ,01 natural sciences ,03 medical and health sciences ,0302 clinical medicine ,Malondialdehyde ,mental disorders ,medicine ,Animals ,Rats, Wistar ,Drug toxicity ,0105 earth and related environmental sciences ,Cardiotoxicity ,Chemical Health and Safety ,business.industry ,Myocardium ,Public Health, Environmental and Occupational Health ,Heart ,General Medicine ,Sleep in non-human animals ,Rats ,Oxidative Stress ,Healthy individuals ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Modafinil is used for the treatment of various sleep disorders; however, its usage among healthy individuals is also increasing. There are a limited number of cardiovascular side effects, including ischemic T-wave changes, dyspnea, hypertension, and tachycardia in the literature. Our research aimed to investigate the dose-dependent subacute cardiovascular effects of modafinil in rats. Thirty-two rats were randomly and equally assigned to a control group (vehicle-treated for 14 days), a subacute low-dose group (SALD, 10 mg/kg for 14 days), a subacute moderate-dose group (SAMD, 100 mg/kg for 14 days), and a subacute high-dose group (SHD, 600 mg/kg for 14 days). The cardiovascular effects of modafinil were evaluated using hemodynamic, biochemical, electrocardiographic, electrophysiologic, and histopathologic parameters. In terms of hemodynamic parameters, heart rate, and systolic/diastolic/mean blood pressure levels, electrophysiological parameters did not reach statistical significance among the groups (p > 0.05). The incidence of T-wave negativity in SAMD and SAHD groups was 25 and 37.5%, respectively. Moreover, one rat per group was affected by an atrioventricular blockage. Malondialdehyde, superoxide dismutase, catalase, and reduced glutathione levels in the heart and vascular tissues, serum troponin-I, and creatine kinase levels were similar between the modafinil-administered groups and the control group (p > 0.05); this indicates that modafinil activated neither oxidative stress nor antioxidant pathway. Also, there was no difference in histopathological parameters between groups (p > 0.05). Supratherapeutic doses of modafinil may have the potential to cause ischemic cardiac damage and atrioventricular blockage, despite inconsistency with literature findings; however, this does not pertain to hemodynamic changes.
- Published
- 2020