Protecting Effects of Rutin and N-Acetyl Cysteine on PON1 Enzyme in Cyclosporine A-Treated Rats: An In-Vivo, In-Vitro, and In-Silico Study

Abstract

Background: Paraoxonase 1 (PON1) is a potent antioxidant enzyme in serum that protects against the oxidation of low-density lipoprotein. This study investigated the effect of N-acetylcysteine (NAC), a synthetic precursor to the natural antioxidant glutathione, and Rutin, a natural antioxidant, on protecting PON1 enzyme activity in rats treated with cyclosporine A (CsA) using experimental and molecular dynamics simulation studies. Materials and Methods: In this study, 48 male rats were divided into six groups, each consisting of eight rats. Groups I, II, and III were CsA-free, while groups IV, V, and VI received 25 mg/kg CsA. Groups V and VI received daily NAC and Rutin (100 mg/kg) via intragastric gavage. After 21 days of treatment, all rats were euthanized, and the high-density lipoprotein parameter was measured using an auto analyzer in serum samples. PON1 enzyme activity was determined by its arylesterase property in serum samples. Docking and molecular dynamics simulation studies were performed using AutoDock V.4.2 and GROMACS 2022 software. Results: CsA decreased the PON1 enzyme arylesterase activity, while this activity increased in the groups that received CsA and Rutin, and/or CsA and NAC. The simulation results showed that all three compounds could bind into the PON1 independently and moderate its activity. Though serum PON1 arylesterase activity decreases in CsA received group, the combination of NAC or Rutin has a synergistic effect in further boosting PON1 aryl esterase enzyme activity when CsA is administered. Conclusion: The present findings indicate that NAC and Rutin have protective effects on the PON1 enzyme in CsA-treated adult rats.