Antioxidant Properties of Novel Lipophilic Fluoroquinolone Compounds Against Oxidative Stress Induced by Acetaminophen and Carbon Tetrachloride in Male Wistar Rats

Oxidative stress is characterised by the production of free radicals in higher amounts than the antioxidant scavenging capacity. This may cause damage to several organs especially the main site of detoxification, the liver. In this study, the antioxidant activity of five novel lipophilic fluoroquinolones (FQs) derivatives was evaluated against oxidative stress induced by acetaminophen (APAP) and carbon tetrachloride (CCl4). Sixty-four male Wistar rats were divided into two oxidative-stress models. FQ compounds (25 mg/kg) were administered six hours after CCl4 or APAP administration. Serum liver enzymes including aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured. Changes in antioxidant parameters were determined in the serum including measurement of total antioxidant status and reduced-glutathione levels as well as catalase, glutathione peroxidase and superoxide dismutase activities. Additionally, molecular docking analyses were performed against catalase, CYP3A4, and Keap-1 to elucidate the potential molecular interactions underlying the observed biological activities. A significant decrease in ALT and AST levels was seen following FQ compound administration in both models. In addition, FQ compounds exhibited excellent antioxidant activity, leading to increased antioxidant enzyme activity, high total antioxidant status, and elevated reduced-glutathione levels. The docking results revealed that compound 4A exhibited the highest binding affinities toward catalase, CYP3A4, and Keap-1. These interactions suggest a possible enhancement of catalase activity, modulation of CYP3A4, and activation of the Keap-1/Nrf2 signalling pathway. Overall, these findings demonstrate the promising therapeutic potential on hepatic injury and oxidative stress of the novel FQ derivatives.