Document Type : Original Article
Authors
1
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, Egypt
2
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Menoufia University, Menoufia, Egypt
3
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt
Abstract
Background: Direct-acting antivirals (DAA) are relatively a new group of drugs. Different studies reported disturbances in lipid metabolism among HCV patients treated with DAA combinations Objective: This study tries to evaluate the short and long term effects of DDA on lipid profile, cardiac enzymes and oxidative stress, as well as, to determine if these effects are disease-related or drug-dependent. Methods: Male Wistar rats were treated with sofosbuvir with or without daclatasvir for four consecutive weeks. Five samples were collected at day 0 (baseline point), another ten samples were obtained after four weeks (end of treatment point) and finally, after six months of treatment, the last ten animals were assigned for follow up point. AST, ALT, lipid profile, serum creatine kinase and troponin were assessed colorimetrically. Moreover, liver tissue content of malondialdehyde was assessed. Results: Results revealed that, at the end of drug therapy period, sofosbuvir whether alone or combined with daclatasvir caused significant increase in total cholesterol, LDL and triglyceride compared to baseline data. These effects were persistent for 20 weeks after the end of treatments. This increase in lipid profile was also correlated with a significant deterioration of cardiac markers such as troponin and creatine kinase –MB and increased oxidative stress. Conclusion: Sofosbuvir and/or daclatasvir elevate lipid profile and cardiac enzymes. These changes are due to the effects of direct acting antiviral agents and independent of hepatitis C virus infection. Consequently, Lipid profile and cardiovascular markers should be monitored during and after drug cessation.
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