Impact of Treatment with Antioxidants as an Adjuvant to Standard Therapy in Patients with Septic Shock: Analysis of the Correlation between Cytokine Storm and Oxidative Stress and Therapeutic Effects

Int J Mol Sci. 2023 Nov 22;24(23):16610. doi: 10.3390/ijms242316610.

Abstract

Cellular homeostasis is lost or becomes dysfunctional during septic shock due to the activation of the inflammatory response and the deregulation of oxidative stress. Antioxidant therapy administered alongside standard treatment could restore this lost homeostasis. We included 131 patients with septic shock who were treated with standard treatment and vitamin C (Vit C), vitamin E (Vit E), N-acetylcysteine (NAC), or melatonin (MT), in a randomized trial. Organ damage quantified by Sequential Organ Failure Assessment (SOFA) score, and we determined levels of Interleukins (IL) IL1β, Tumor necrosis factor alpha (TNFα), IL-6, monocyte chemoattractant protein-1 (MCP-1), Transforming growth factor B (TGFβ), IL-4, IL-10, IL-12, and Interferon-γ (IFNγ). The SOFA score decreased in patients treated with Vit C, NAC, and MT. Patients treated with MT had statistically significantly reduced of IL-6, IL-8, MCP-1, and IL-10 levels. Lipid peroxidation, Nitrates and nitrites (NO3- and NO2-), glutathione reductase, and superoxide dismutase decreased after treatment with Vit C, Vit E, NAC, and MT. The levels of thiols recovered with the use of Vit E, and all patients treated with antioxidants maintained their selenium levels, in contrast with controls (p = 0.04). The findings regarding oxidative stress markers and cytokines after treatment with antioxidants allow us to consider to future the combined use of antioxidants in a randomized clinical trial with a larger sample to demonstrate the reproducibility of these beneficial effects.

Keywords: antioxidants; cytokines; melatonin; septic shock.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Acetylcysteine / therapeutic use
  • Adjuvants, Immunologic / therapeutic use
  • Antioxidants / therapeutic use
  • Ascorbic Acid / therapeutic use
  • Cytokine Release Syndrome / drug therapy
  • Humans
  • Interleukin-10
  • Interleukin-6
  • Melatonin* / therapeutic use
  • Oxidative Stress
  • Reproducibility of Results
  • Shock, Septic* / drug therapy
  • Vitamin E / therapeutic use

Substances

  • Antioxidants
  • Interleukin-6
  • Interleukin-10
  • Ascorbic Acid
  • Vitamin E
  • Acetylcysteine
  • Melatonin
  • Adjuvants, Immunologic

Grants and funding

This work was supported by Centro Medico A.B.C. Observatorio Project (ABC number 18-19) and Instituto Nacional de Cardiologia Ignacio Chavez.