June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Beta glucogallin, a plant-derived antioxidant and anti-inflammatory agent, alleviates corneal injury from chloropicrin exposure.
Author Affiliations & Notes
  • David A Ammar
    Ophthalmology, Univ of Colorado Denver, Aurora, Colorado, United States
  • Dinesh G Goswami
    Pharmaceutical Sciences, Univ Colorado Denver, Aurora, Colorado, United States
  • Rama Kant
    Pharmaceutical Sciences, Univ Colorado Denver, Aurora, Colorado, United States
  • Kristofer S Fritz
    Pharmaceutical Sciences, Univ Colorado Denver, Aurora, Colorado, United States
  • Daniel V LaBarbera
    Pharmaceutical Sciences, Univ Colorado Denver, Aurora, Colorado, United States
  • Rajesh Agarwal
    Pharmaceutical Sciences, Univ Colorado Denver, Aurora, Colorado, United States
  • J. Mark Petrash
    Ophthalmology, Univ of Colorado Denver, Aurora, Colorado, United States
  • Neera Tewari-Singh
    Pharmaceutical Sciences, Univ Colorado Denver, Aurora, Colorado, United States
  • Footnotes
    Commercial Relationships   David Ammar, i2C Solutions (SBIR) (F); Dinesh Goswami , None; Rama Kant, None; Kristofer Fritz, None; Daniel LaBarbera, Univ of Colorado Denver (P); Rajesh Agarwal, None; J. Mark Petrash, Univ of Colorado Denver (P); Neera Tewari-Singh, i2C Solutions (SBIR) (F)
  • Footnotes
    Support  This work is supported in part a Challenge Grant from Research to Prevent Blindness to the Department of Ophthalmology, and by an SBIR Grant W81XWH-15-C-0138 (DoD).
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 1177. doi:
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    • Get Citation

      David A Ammar, Dinesh G Goswami, Rama Kant, Kristofer S Fritz, Daniel V LaBarbera, Rajesh Agarwal, J. Mark Petrash, Neera Tewari-Singh; Beta glucogallin, a plant-derived antioxidant and anti-inflammatory agent, alleviates corneal injury from chloropicrin exposure.. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1177.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : There are no effective therapies to alleviate corneal injury from chloropicrin (CCl3NO2, trichloronitromethane, CP) exposure, a broad spectrum fumigant and pesticide which has been employed as a warfare agent. CP exposure-induced eye injury is associated with lacrimation and inflammation which involves corneal edema and damage. Based on completed mechanistic studies, we tested the efficacy of beta-glucogallin (BGG), a natural antioxidant and anti-inflammatory agent with anti-lipid peroxidation and carbonyl scavenger properties, hypothesized as an effective therapy against CP-induced corneal injury.

Methods : Efficacy studies were carried out in primary human corneal epithelial (HCE) cells following 30 min exposure to 50 µM CP with and without treatment with either 50 µM BGG or a perfluorocarbon oxygen emulsion. Western blot analysis was assessed 24 h post exposure to determine the CP-induced effects on various molecular markers. CP injury was induced in ex vivo rabbit corneas by exposing the corneas to 200 nmol CP for 2 h, followed by washing and treatment with 10 µl of 500 µM BGG and thereafter every 6 h for 24 h. Corneal tissue was prepared for subsequent histological (H&E staining), immunohistochemical, and western blot analyses.

Results : In primary HCE cells, BGG treatment reduced CP-induced increases in cleaved PARP by 35%, H2A.X phosphorylation by 40%, MAPK-JNK phosphorylation by 43%, protein carbonylation (biotin hydrazide) by 56%, and a complete reversal in lipid peroxidation (4-hydroxynonenal, 4-HNE). Preliminary studies in HCE cells indicate that application of the oxygen emulsion reduced CP-induced phosphophorylated-p53 and cleaved PARP. In ex vivo rabbit corneas, BGG treatment resulted in a 31% reversal in CP-induced epithelial degradation and complete reversal in CP-induced COX-2 expression and protein carbonylation.

Conclusions : These data suggest strong potential for BGG in reversing CP-induced lipid peroxidation and protein carbonylation as well as reducing epithelial degradation and inflammation in rabbit cornea when given 2 h after CP exposure. Further studies expanding the examination of BGG alone or in combination with oxygen emulsion in alleviating CP- and other chemical agents-induced ocular injury, and delineation of its targets and pathways is justified.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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