Lactoferrin alleviates oxidative stress and endoplasmic reticulum stress induced by autoimmune thyroiditis by modulating the mTOR pathway in the thyroid

J Endocrinol Invest. 2025 Apr;48(4):861-876. doi: 10.1007/s40618-024-02505-0. Epub 2024 Nov 22.

Abstract

Autoimmune thyroiditis (AITD) is a prevalent autoimmune disorder characterized by the immune system's attack on thyroid tissue, potentially leading to thyroid dysfunction, with a current lack of effective treatment modalities. Lactoferrin, a crucial functional dietary component obtainable from food sources, primarily exists in mammalian milk. We aim to investigate whether dietary supplementation with lactoferrin can protect the thyroid in Experimental Autoimmune Thyroiditis (EAT) rats. Our study reveals significantly elevated levels of oxidative stress (OS) and endoplasmic reticulum stress (ERS) in the AITD. Lactoferrin markedly reduces OS and infiltration of inflammatory cells in the thyroid tissue of EAT rats. Furthermore, lactoferrin inhibits ERS levels in the thyroid of EAT rats and alleviates cellular apoptosis. In vivo and in vitro experiments elucidate that its protective effect is primarily achieved through the inhibition of mTOR signaling pathway activation. In summary, lactoferrin, a nutrient readily obtainable from food sources, appears to be effective in mitigating thyroid damage in AITD.

Keywords: Autoimmune thyroiditis; Endoplasmic reticulum stress; Lactoferrin; MTOR pathway; Oxidative stress.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Disease Models, Animal
  • Endoplasmic Reticulum Stress* / drug effects
  • Humans
  • Lactoferrin* / pharmacology
  • Male
  • Oxidative Stress* / drug effects
  • Rats
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases* / metabolism
  • Thyroid Gland* / drug effects
  • Thyroid Gland* / metabolism
  • Thyroid Gland* / pathology
  • Thyroiditis, Autoimmune* / drug therapy
  • Thyroiditis, Autoimmune* / metabolism
  • Thyroiditis, Autoimmune* / pathology

Substances

  • Lactoferrin
  • TOR Serine-Threonine Kinases
  • mTOR protein, rat