L-carnosine mitigates interleukin-1α-induced dry eye disease in rabbits via its antioxidant, anti-inflammatory, antiapoptotic, and antifibrotic effects

Cutan Ocul Toxicol. 2021 Sep;40(3):241-251. doi: 10.1080/15569527.2021.1935995. Epub 2021 Jun 16.

Abstract

Objective: To elucidate the implications of L-carnosine on interleukin-1α (IL-1α)-induced inflammation of lacrimal glands (LGs).

Materials and methods: Forty rabbits were divided equally into four groups: control group (G1), IL-1α (G2), L-carnosine (G3), and L-carnosine plus IL-1α (G4). Several clinical, histopathological, immunohistochemical, morphometric, and biochemical investigations were performed, followed by statistical analysis to diagnose the presence of dry eye disease (DED).

Results: The LGs of G2 rabbits showed degeneration of the acinar cells, increased deposition of collagen fibers, and marked immunoexpression of FasL; elevated levels of interferon-γ, tumor necrosis factor-α, transforming growth factor-β1, and malondialdehyde; and decreased levels of glutathione peroxidase, superoxide dismutase, catalase, and reactive oxygen species compared with those of G1 rabbits. In contrast, administration of L-carnosine to G4 rabbits revealed marked improvement of all previously harmful changes in G2 rabbits, indicating the cytoprotective effects of L-carnosine against IL-1α-induced inflammation of LGs.

Conclusions: IL-1α induced inflammation of LGs and eye dryness via oxidative stress, proinflammatory, apoptotic, and profibrotic effects, whereas L-carnosine mitigated DED through antioxidant, anti-inflammatory, antiapoptotic, and antifibrotic effects on LGs. Therefore, this work demonstrates for the first time that L-carnosine may be used as adjuvant therapy for the preservation of visual integrity in patients with DED.HighlightsIL-1α induced dry eye disease through its oxidative stress, proinflammatory, apoptotic and profibrotic effects on the lacrimal glands of rabbit.L-carnosine has antioxidant, anti-inflammatory, antiapoptotic and antifibrotic effects.L-carnosine mitigated IL-1α induced dry eye disease via elevating the levels of FasL, IFN-γ, TNF-α, TGFβ1 and MDA as well as reducing the levels of antioxidants (GPx, SOD, and catalase) and ROS in the lacrimal glands of rabbit.L-carnosine could be used as a novel adjuvant therapy for the treatment of dry eye disease.

Keywords: L-carnosine; Lacrimal glands; anti-inflammatory; antiapoptotic; antifibrotic; dry eye disease; interleukin-1α.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Antioxidants / pharmacology*
  • Antioxidants / therapeutic use
  • Apoptosis / drug effects
  • Apoptosis / immunology
  • Carnosine / pharmacology*
  • Carnosine / therapeutic use
  • Disease Models, Animal
  • Dry Eye Syndromes / drug therapy*
  • Dry Eye Syndromes / immunology
  • Dry Eye Syndromes / pathology
  • Humans
  • Interleukin-1alpha / administration & dosage
  • Interleukin-1alpha / immunology*
  • Lacrimal Apparatus / drug effects
  • Lacrimal Apparatus / immunology
  • Lacrimal Apparatus / pathology
  • Male
  • Oxidative Stress / drug effects
  • Rabbits
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / immunology

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • IL1A protein, human
  • Interleukin-1alpha
  • Recombinant Proteins
  • Carnosine