Aim. This study aimed to investigate the effects of combined quercetin and resveratrol administration on markers of oxidative and nitrosative stress in the liver of rats subjected to surgical trauma following prolonged stress exposure.

Materials and methods. The study was conducted on 35 adult male Wistar rats, which were randomly assigned to five experimental groups: intact animals (control, Group 1); rats subjected to single prolonged stress (SPS) followed by laparotomy (Group 2); animals exposed to SPS and laparotomy and treated with a water-soluble form of quercetin (20 mg/kg body weight, Group 3), resveratrol (5 mg/kg body weight, Group 4), and a combination of quercetin and resveratrol (Group 5). Hepatic oxidative-nitrosative stress was assessed by measuring superoxide anion radical (O2•–) production, total nitric oxide synthase (NOS) activity, the activities of constitutive and inducible NOS isoforms (cNOS and iNOS), and the concentration of peroxynitrites of alkali and alkaline-earth metals.

Results. Combined exposure to SPS and surgical trauma induced a marked oxidative-nitrosative imbalance in the liver, manifested by excessive superoxide and peroxynitrite production, mitochondrial redox dysfunction, iNOS overactivation, and profound cNOS uncoupling. Monotherapy with either water-soluble quercetin or resveratrol partially alleviated these stress-induced alterations by reducing O2•– generation, suppressing iNOS activity, and improving cNOS coupling, confirming their hepatoprotective effects under conditions of combined psycho-emotional and surgical stress. In contrast, combined quercetin-resveratrol administration provided substantially greater protection, resulting in near-complete normalization of mitochondrial O2•– production, full restoration of cNOS activity and coupling, and a marked reduction in hepatic peroxynitrite accumulation.

Conclusions. These findings indicate a synergistic interaction between the two polyphenols, quercetin and resveratrol in restoring hepatic redox and nitric oxide homeostasis.