Paraoxonase-1: How a xenobiotic detoxifying enzyme has become an actor in the pathophysiology of infectious diseases and cancer

Chem Biol Interact. 2023 Aug 1:380:110553. doi: 10.1016/j.cbi.2023.110553. Epub 2023 May 16.

Abstract

Both infectious and non-infectious diseases can share common molecular mechanisms, including oxidative stress and inflammation. External factors, such as bacterial or viral infections, excessive calorie intake, inadequate nutrients, or environmental factors, can cause metabolic disorders, resulting in an imbalance between free radical production and natural antioxidant systems. These factors may lead to the production of free radicals that can oxidize lipids, proteins, and nucleic acids, causing metabolic alterations that influence the pathogenesis of the disease. The relationship between oxidation and inflammation is crucial, as they both contribute to the development of cellular pathology. Paraoxonase 1 (PON1) is a vital enzyme in regulating these processes. PON1 is an enzyme that is bound to high-density lipoproteins and protects the organism against oxidative stress and toxic substances. It breaks down lipid peroxides in lipoproteins and cells, enhances the protection of high-density lipoproteins against different infectious agents, and is a critical component of the innate immune system. Impaired PON1 function can affect cellular homeostasis pathways and cause metabolically driven chronic inflammatory states. Therefore, understanding these relationships can help to improve treatments and identify new therapeutic targets. This review also examines the advantages and disadvantages of measuring serum PON1 levels in clinical settings, providing insight into the potential clinical use of this enzyme.

Keywords: Infection; Inflammation; Metabolism; Paraoxonase-1; Pathophysiology.

Publication types

  • Review

MeSH terms

  • Aryldialkylphosphatase* / metabolism
  • Humans
  • Inflammation
  • Lipoproteins, HDL / metabolism
  • Neoplasms*
  • Oxidative Stress
  • Xenobiotics

Substances

  • Aryldialkylphosphatase
  • Xenobiotics
  • Lipoproteins, HDL
  • PON1 protein, human