Evaluation of the protective role of resveratrol against sepsis caused by LPS via TLR4/NF-κB/TNF-α signaling pathways: Experimental study

Okan A., DOĞANYİĞİT Z., YILMAZ S., UÇAR S., Arikan Söylemez E. S., Attar R.

Cell Biochemistry and Function, vol.41, no.4, pp.423-433, 2023 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 41 Issue: 4
  • Publication Date: 2023
  • Doi Number: 10.1002/cbf.3790
  • Journal Name: Cell Biochemistry and Function
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.423-433
  • Keywords: NF-kappa B, oxidative stress markers, resveratrol, sepsis, TLR4 signaling, TNF-alpha
  • Yozgat Bozok University Affiliated: Yes


The development and progression of sepsis are multifactorial and influence the immunological, endocrine, and cardiovascular systems of the body. Our knowledge of the key mechanisms involved in the pathogenesis of sepsis has expanded exponentially, yet this still needs to be translated into effective targeted therapeutic regimes. In the present study, we aimed to determine whether resveratrol has positive effects in the experimental sepsis rat model. Twenty-eight male Spraque–Dawley rats were randomly divided into four groups (n = 7) as follows: control, lipopolysaccharide (LPS) (30 mg/kg dose), resveratrol, and LPS and resveratrol. After the experiment, liver and kidney tissues were collected for histopathological evaluation, blood serums were collected to measure malondialdehyde levels with enyzme-linked immunosorbent assay, and Toll-like receptor-4 (TLR4), tumor necrosis factor-α (TNF-α), nuclear factor-κB (NF-κB) immunoreactivity density was evaluated immunohistochemically. In addition, messenger RNA expression levels for TLR4, TNF-α, NF-κB, interleukin-1β, and interleukin 6 were measured. In addition, the damage observed in liver and kidney tissue was determined by AgNOR (argyrophilic nucleolar organizer regions) staining. LPS application caused severe tissue damage, oxidative stress, and increased the expressions of proinflammatory proteins and genes we evaluated, while resveratrol application eliminated these negativities. Resveratrol has been proven to suppress the TLR4/NF-κB/TNF-α pathway, a possible therapeutic signaling pathway that is important in initiating the inflammatory response in an animal model of sepsis.