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

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.

Highlights

• IL-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:

• Lacrimal glands
• dry eye disease
• interleukin-1α
• L-carnosine
• anti-inflammatory
• antiapoptotic
• antifibrotic

Acknowledgements

The authors gratefully acknowledge Qassim University, represented by the Deanship of Scientific Research, for the material support of this research under grant number [1411-CAMS- 2016-1-12-1] during the academic year 1437AH/ 2017 AD. Additionally, the researchers thank Mr. Sayed Elsheikh and Dr. Arif Khan for their generous technical help during this work.

Disclosure statement

The authors report no conflict of interest.

Data availability statement

All relevant data have been provided in the manuscript.