Amelioration of endotoxin-induced inflammatory toxic response by a metal chelator in rat eyes

Mohammad Shoeb, Min Zhang, Tianlin Xiao, Misha Syed, Naseem Ansari

Research output: Contribution to journalArticle

Abstract

PURPOSE. Metal ions play a key role in exacerbating toxicity associated with oxidative stress and inflammation. This study examines the effects of a formulation containing the metal chelator ethylenediaminetetraacetic acid (EDTA) and permeability enhancer methyl sulfonyl methane (MSM) on the early course of inflammation in endotoxin-induced uveitis (EIU). The proprietary MSM/EDTA formulation of Livionex, Inc., which was used for this study, is covered by several patents and pending patent applications. METHODS. EIU was induced by using subcutaneous injection of lipopolysaccharide (LPS) into the thighs of Lewis rats. Treatment consisted of topical application to the eyes of either PBS or eye drops designated as ME that contain EDTA and MSM. Clinical signs of uveitis were monitored at 6 and 24 hours postinjection. Oxidative and inflammatory markers were evaluated by ELISA or immunohistochemistry. RESULTS. Rats treated with ME showed fewer clinical signs of uveitis including reduced miosis, fibrinous exudates, and dilated blood vessels. The aqueous humor of treated rats contained fewer leukocytes, lower protein levels, and less PGE2. Formation of protein adducts with the lipid peroxidation end-product, 4-hydroxynonenal, expression of NF-jB, TNF-α, and MMP-9 were all reduced in rats treated with ME. CONCLUSIONS. Our results indicate that ME eye drops downregulate the ocular inflammatory response in LPS treated rats, suggesting that induction of EIU involves metal ions and chelation therapy with ME is a potential treatment for uveitis.

LanguageEnglish (US)
Pages31-38
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume59
Issue number1
DOIs
StatePublished - Jan 1 2018

Fingerprint

Poisons
Uveitis
Chelating Agents
Endotoxins
Metals
Methane
Edetic Acid
Ophthalmic Solutions
Lipopolysaccharides
Ions
Chelation Therapy
Miosis
Inflammation
Patents
Aqueous Humor
Exudates and Transudates
Subcutaneous Injections
Thigh
Matrix Metalloproteinases
Dinoprostone

Keywords

  • EDTA
  • Eyes
  • Inflammation
  • Metal chelation
  • Oxidative stress
  • Uveitis

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Amelioration of endotoxin-induced inflammatory toxic response by a metal chelator in rat eyes. / Shoeb, Mohammad; Zhang, Min; Xiao, Tianlin; Syed, Misha; Ansari, Naseem.

In: Investigative Ophthalmology and Visual Science, Vol. 59, No. 1, 01.01.2018, p. 31-38.

Research output: Contribution to journalArticle

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