Tear and serum MMP-9 and serum TIMPs levels in the severe sulfur mustard eye injured exposed patients

Int Immunopharmacol. 2019 Dec:77:105812. doi: 10.1016/j.intimp.2019.105812. Epub 2019 Oct 31.

Abstract

Introduction: Sulfur mustard (SM) intoxication produces local and systemic changes in the human body. In this study, the relationship between tear and serum matrix metalloproteinase (MMP)-9 and serum tissue inhibitors of metalloproteinases (TIMPs) are assessed in serious eye-injured SM-exposed casualties.

Methods: A group of 128 SM-exposed patients with serious ocular injuries in three subgroups (19 mild, 31 moderate, and 78 severe cases) is compared with 31 healthy controls. Tear and ocular status and serum MMPs and MMP-9/TIMPs complex levels were evaluated using enzyme-linked immunosorbent assay (ELISA).

Results: Serum level of MMP-9 was significantly higher in the SM-exposed group compared to the control group (P = 0.009). Mean serum MMP-9 level in the SM-exposed group with ocular abnormalities was significantly higher than that in the SM-exposed group without ocular abnormalities. SM-exposed people with corneal calcification had significantly higher serum MMP-9/TIMP-1 level compared to the SM-exposed ones without this problem (P = 0.045). The SM-exposed group with severe ocular injuries had significantly higher MMP-9/TIMP-1 than the controls (P = 0.046). The SM-exposed group had significantly lower levels of MMP-9/TIMP-4 complex than the controls (P < 0.001). The SM-exposed group with tear meniscus and fundus abnormality had significantly higher MMP-9/TIMP-4 levels than the SM-exposed group without these problems (P = 0.009 and P = 0.020).

Conclusion: Serum MMP-9 level had increased in SM-exposed groups with ocular problems, while TIMP-1 and TIMP-2 levels had remained unchanged. Serum TIMP-4 drastically decreased in SM-exposed group, which clearly explains the severity of the systemic and ocular damages.

Keywords: Matrix metalloproteinase-9 (MMP-9); Ocular injury; Sulfur mustard; Tissue inhibitors of metalloproteinase-1 (TIMP-1); Tissue inhibitors of metalloproteinase-4 (TIMP-4).

MeSH terms

  • Chemical Warfare Agents / toxicity*
  • Eye Injuries / blood
  • Eye Injuries / chemically induced
  • Eye Injuries / metabolism*
  • Humans
  • Matrix Metalloproteinase 9 / blood
  • Matrix Metalloproteinase 9 / metabolism*
  • Mustard Gas / toxicity*
  • Severity of Illness Index
  • Tears / metabolism*
  • Tissue Inhibitor of Metalloproteinases / blood
  • Tissue Inhibitor of Metalloproteinases / metabolism*

Substances

  • Chemical Warfare Agents
  • Tissue Inhibitor of Metalloproteinases
  • MMP9 protein, human
  • Matrix Metalloproteinase 9
  • Mustard Gas