Modulating Role of Resveratrol in Metabolic and Inflammatory Dysregulation Caused by Surgical and Psychoemotional Stress in Rats.

Objectives

This study investigates the effects of resveratrol on systemic inflammatory, oxidative, and metabolic responses in a rat model that combines surgical trauma with prior exposure to Single Prolonged Stress (SPS), an established experimental protocol for modeling post-traumatic stress disorder (PTSD).

Methods

Male Wistar rats (n = 21) were randomly assigned to three groups: (I) control (polyvinylpyrrolidone, PVP), (II) SPS + laparotomy + PVP), and (III) SPS + laparotomy + resveratrol. Resveratrol (5 mg/kg of body weight/day) or vehicle was administered intragastrically for seven days. Serum concentrations of cortisol, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), glucose, insulin, lipid fractions, and thiobarbituric acid-reactive substances (TBA-RS) were determined by enzyme-linked immunosorbent assay and spectrophotometric methods. Insulin resistance was assessed using the homeostatic model assessment of insulin resistance (HOMA-IR) index.

Results

Combined SPS and surgical trauma induced a pronounced systemic inflammatory response characterized by elevated cortisol (+138%), TNF-α (+83%), IL-6 (+465%), and ceruloplasmin (+71%), as well as hyperglycemia, hyperinsulinemia, increased HOMA-IR, and atherogenic dyslipidemia with reduced high-density lipoprotein cholesterol (HDL-CH; -64%), elevated triglycerides (TGs; +216%), and very low-density lipoprotein cholesterol (VLDL-CH; +218%). Marked activation of lipid peroxidation was observed, as indicated by increased TBA-RS levels before and after incubation. Resveratrol administration significantly decreased cortisol (-45%), TNF-α (-47%), and IL-6 (-85%), normalized the IL-10/IL-6 ratio, and reduced ceruloplasmin levels (-13%). The compound improved insulin sensitivity (HOMA-IR -50%), elevated HDL-CH (+115%), and lowered TGs and VLDL-CH (-44%). It also attenuated both basal and inducible lipid peroxidation (TBA-RS -11% and -13%), indicating restoration of antioxidant capacity.

Conclusions

Thus, resveratrol effectively counteracts the neuroendocrine, inflammatory, and metabolic disturbances induced by combined PTSD-like stress and surgical trauma.