Treatment of Experimental Granulomatous Uveitis by Lipoxygenase and Cyclo-oxygenase Inhibitors

Rao, Narsing A.; Patchett, Richard; Fernandez, Mary Ann; Sevanian, Alex; Kunkel, S. L.; Marak, George E.

doi:10.1001/archopht.1987.01060030133043

Cited by 25 publications

(12 citation statements)

References 10 publications

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“…The concentration of NDGA and of indomethacin used in this study was based on previously reported investigations [10,13]. Both drugs are known to be nonspecific in hibitors of arachidonic acid metabolism when used at high concentrations [ 13].…”

Section: Discussionsupporting

confidence: 43%

“…How ever. at the doses employed in the current study, NDGA and indomethacin have been shown to selectively inhibit the lipoxygenase and cyclo-oxygenase pathways of the arachi donic acid metabolism, respectively [ 10,13]. Histologically, there was suppression of in flammation in the choroid in the NDGAtreated groups compared with that in the control or the indomethacin-treated groups of rats.…”

Section: Discussionsupporting

confidence: 40%

“…There is no substantial differ ence in the lysosomal enzyme activity be tween control animals and those treated with cyclo-oxygenase or lipoxygenase inhibitors. The granulomatous inflammation, however, was reduced with lipoxygenase inhibitors in comparison with the other treatments, which correlates with our previous findings [10], These findings suggest that although arachidonic acid metabolites regulate the in flammatory response in lens-induced granu lomatous uveitis, they do not play a major role in the expression of lysosomal enzymes during development of the granulomatous inflammation observed in our model of uveitis.…”

Section: Discussionmentioning

confidence: 46%

“…Histologically, there was suppression of in flammation in the choroid in the NDGAtreated groups compared with that in the control or the indomethacin-treated groups of rats. This was similar to our earlier obser vation [10].…”

Section: Discussionmentioning

confidence: 50%

“…The disease is best manifested in rats, but can be produced also in guinea pigs and mice [9], In rats, the pigmented Brown Norway strain develops a severe reaction around the lens, along with marked thickening of the choroid with mononuclear cells and multiple epithelioid cell granulomas, whereas albino strains pro duce an Arthus reaction around the lens [9], In an earlier study, we observed that various arachidonic acid metabolite inhibitors have modulating effects on the expression of gran ulomatous uveitis in the Brown Norway rat [10], The lipoxygenase inhibitors nafazatrom and nordihydroguaiaretic acid (NDGA) markedly suppressed the granulomatous in flammation, whereas the cyclo-oxygenase in hibitor indomethacin enhanced inflamma tion [10], In the study described herein, we investigated the effect of these inhibitors on the expression of lysosomal enyzmes in the choroidal inflammation that is characteristic of experimental lens-induced granulomatous uveitis.…”

mentioning

confidence: 47%

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Histochemical Analysis of Experimental Granulomatous Uveitis

Kristeva

Biswas²,

Pararajasegaram³

et al. 1991

Ophthalmic Res

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We have previously demonstrated the effects of various inhibitors of arachidonic acid metabolism on experimental lens-induced granulomatous uveitis. In the present study, we investigated the effect of these same inhibitors on the expression of lysosomal enzymes at different stages of choroidal inflammation in experimental lens-induced granulomatous uveitis and compared this to the inflammation observed at each stage examined. Lysosomal enzymes such as acid phosphatase, β-glucuronidase and succinate dehydrogenase are known to be liberated during the maturation of mononuclear phagocytes to epithelioid cell granulomas. Although animals treated with nordihydroguaiaretic acid showed less severe inflammation than did indomethacin-treated or control animals, none of these agents appeared to affect the expression of acid phosphatase and β-glucuronidase, as determined histochemically. Succinate dehydrogenase could not be detected in any of the eyes examined, even though sections of liver and kidney from these same animals were positive for this enzyme.

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Section: Discussionsupporting

confidence: 43%

Section: Discussionsupporting

confidence: 40%

Section: Discussionmentioning

confidence: 46%

Section: Discussionmentioning

confidence: 50%

mentioning

confidence: 47%

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Histochemical Analysis of Experimental Granulomatous Uveitis

Kristeva

Biswas²,

Pararajasegaram³

et al. 1991

Ophthalmic Res

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Topical Anti-inflammatory Agents in an Animal Model of Microbial Keratitis

et al. 1990

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Eicosanoids and nitric oxide influence induction of reactive gliosis from spreading depression in microglia but not astrocytes

Caggiano

Kraig

1996

J. Comp. Neurol.

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Microglia and astrocytes are transformed into reactive glia (RG) by brain disease and normal function. Eicosanoids and nitric oxide (NO), two intercellular mediators, may influence gliosis. We investigated how drugs that alter production of these paracrine signals effect induction of glial reactivity from spreading depression. Unilateral (left) neocortical spreading depression was induced in 95 halothane anesthetized rats by intracortical injections of 0.5 M KCl, with or without drug treatment (five animals/group). Immunohistochemical staining (IS) intensity using the OX-42 and anti-glial fibrillary acidic protein (GFAP) antibodies determined reactivity in microglia and astrocytes, respectively. After 3 days, brains were processed for OX-42 and GFAP-IS and mean optical densities (OD) of IS were measured. Average OD's (for OX-42) and the log ratio (left/right) of OD's (OX-42 and GFAP) were compared to normal animals. Spreading depression induced significant log ratios for both OX-42- and GFAP-IS (P's < 0.01). However, dexamethasone (a glucocorticoid), nordihydroguaiaretic acid (a lipoxygenase inhibitor), and nitroprusside (a NO donor) prevented significant left sided and log ratio OD values for microglia (P's > 0.05). L-Name, a NO synthase inhibitor, caused significant increases in left and right OD's for microglia (P's < 0.05). Mepacrine, a phospholipase A2 inhibitor, Indomethacin, a cyclooxygenase inhibitor, and phenylephrine, an adrenergic agonist, did not prevent induction of significant OX-42 log ratios (P's < 0.01, 0.05, 0.01), and resulted in increases in left side OD's (P's < 0.01, 0.05, 0.05). Significant GFAP log ratios occurred after spreading depression in all drug groups, P's < 0.01. Thus, induction of reactivity in microglia is more sensitive to eicosanoids and NO than in astrocytes.

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Treatment of Experimental Granulomatous Uveitis by Lipoxygenase and Cyclo-oxygenase Inhibitors

Cited by 25 publications

References 10 publications

Histochemical Analysis of Experimental Granulomatous Uveitis

Histochemical Analysis of Experimental Granulomatous Uveitis

Topical Anti-inflammatory Agents in an Animal Model of Microbial Keratitis

Eicosanoids and nitric oxide influence induction of reactive gliosis from spreading depression in microglia but not astrocytes

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