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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. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
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.
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.
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.
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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