Possible Hepatotoxic Effects In Adult Male Albino Rats On Combination Of Ivermectin And Paracetamol Drugs Used In COVID-19 Infection Management Protocol

Document Type : Original Article

Authors

1 forensic medicine and clinical toxicology, faculty of medicine, zagazig university

2 Cairo 4

3 human anatomy and embryology, faculty of medicine, zagazig university

Abstract

Introduction: Ivermectin (IVM) and paracetamol(APAP) are among drugs used for treatment of mild and moderate cases of covid-19 infection. Aim: this study aimed to evaluate the potential hepatotoxic effects on combination of both paracetamol and ivermectin in adult male albino rats. Methodology: fifty adult male albino rats were divided into control groups (negative & Positive) and IVM&APAP treated group which included thirty rats & subdivided equally into 3 subgroups (III A, B, C). Each rat received orally 3.7mg/kg/day of ivermectin concomitantly with 370mg/kg /day of paracetamol (groups III A, B, C were sacrificed after 7 days, 14 days and 28 days respectively). Serum levels of aminotransferases ALT, AST, glutamate dehydrogenase (GLDH) & Hyaluronan (HA), Histopathological examination of liver & immunohistochemical staining for inducible nitric oxide synthase (iNOS) were performed. Results: HA was elevated after 7 days followed by GLDH which increased after 14 days while aminotransferases levels increase only after 28 days of combined IVM&APAP treatment. After 7 days, the histopathological changes in IVM &APAP treated group was restricted to congestion of central vein with some vaculation in the hepatocytic cytoplasm then aggravated with increased duration of treatment to periportal fibrosis, inflammatory infiltration areas and necrotic foci. Conclusion: Combination of IVM&APAP induced liver injury, detected 7 days after treatment by HA level and accompanied by histopathological changes which became more severe with increasing duration of treatment. IVM&APAP should be used cautiously to avoid possibility of aggravation of liver injury which is believed to be one of covid-19 complications

Keywords