The effect of N-acetyl cysteine and doxycycline on TNF-α-Rel-a inflammatory pathway and downstream angiogenesis factors in the cornea of rats injured by 2-chloroethyl-ethyl sulfide

Cornea injury of sulfur mustard (SM) is considered as the most devastating injuries to the eye. This study aimed to evaluate the single and combined effects of N-acetyl cysteine (NAC) and doxycycline on the inflammatory pathway and cornea neovascularization (CNV) in the rat model of SM-injured cornea. The right cornea of male Sprague–Dawley rats was subjected to 2-chloroethyl-ethyl sulfide (CEES). Rats were topically treated with a single and combined of 0.5% NAC and 12.5 μg/ml doxycycline and examined at 3rd, 15th, and 21st days. The activity of three antioxidant enzymes was analyzed in the cornea of different groups. Real-time PCR was performed to measure gene expression of inflammatory factors (tnf-α, rel-a & cxcl-1) and angiogenesis factors (vegf-a, mmp2,9) in the cornea lysates. The histological and opacity assessments were also carried out. The activity of antioxidant enzymes significantly declined 3 days after the CEES damage. NAC eye drop recovered the enzyme activity on the 21st day of treatment (p-value tnf-α and rel-a genes significantly increased after CEES cornea exposure, while NAC declined their expression on the 7th and 21st days. The CNV score and angiogenesis factor expression were decreased in the long term by single and combined treatments (p-value NAC and doxycycline eye drop could improve the CNV complication. Also, NAC was an effective treatment against the inflammatory pathway involved in CEES-injured cornea.