Effect of anti-inflammatory compounds on edema formation and myeloperoxidase activity in the arachidonic acid-induced ear model in the mouse

Abstract

The arachidonic acid (AA)-induced ear edema model in the mouse has been demonstrated as an effective in vivo experimental tool to screen compounds showing anti-inflammatory activity. Since neutrophil influx is a component of the inflammatory reaction, we have modified this assay by quantitating myeloperoxidase (MPO) levels which reflect neutrophil accumulation in the edematous biopsies of the mouse ear. Our work has shown that orally administered 5-lipoxygenase inhibitors, dual inhibitors (CO/LO), and steroids dose-dependently inhibit both edema formation and MPO activity, whereas oral activity is not seen with NSAID's. There is a good correlation between the inhibition of edema formation and of MPO activity by these compounds. Thus, measurement of MPO, in addition to the AA-induced edema in the mouse ear, can provide another parameter to profile potential anti-inflammatory compounds.

ER-34122, a novel dual 5-lipoxygenase/cyclooxygenase inhibitor with potent anti-inflammatory activity in an arachidonic acid-induced ear inflammation model

“…These results indicate that LOX metabolites are mainly involved in this inflammation model, and the potent anti-inflammatory activity of ER-34122 can be ascribed to its inhibition of LOX products generation. Our results showing lack of inhibitory activity of indomethacin in the ear inflammation model are consistent with the findings of Griswold et al [33,43] and Kotyuk et al [44]. However, these results, including our results, are not consistent with the findings of Crummey et al [41] and Carlson et al [42] that topical administration of indomethacin and/or naproxen inhibited edema formation in the ear inflammation.…”

Characterization of fluoroquinolone-induced Achilles tendon toxicity in rats: comparison of toxicities of 10 fluoroquinolones and effects of anti-inflammatory compounds

“…Considering the inhibitory effect of AA on pefloxacin-induced tendon lesions in the present study, we suspect that leukotrienes, which are 5-LO products, play a role in the development of the lesion. Kotyuk et al (13) reported that acid-induced ear edema in mice was prevented by treatment with dual CO-LO inhibitors, 5-LO inhibitors, and steroids but not with CO inhibitors. Similar effects by the LO or the CO inhibitor were demonstrated in brain edema in rats (3).…”

1,5-Disubstituted Indazol-3-ols with Anti-Inflammatory Activity

“…Neutrophils migrate into the dermis of the ear 30 min after AA-application and reach the maximum concentration 1 h when edema culminates. The quantity of polymorphonuclear leukocytes (PMNL) migrating into the inflammatory sites corresponds to the degree of development of edema [10,11] . 5-LOX inhibitors are known to reduce the development of edema in mice [12] .…”

“…The development of the ear edema was calculated by subtracting the thickness of the left ear (vehicle control) from that of the right ear (treated ear). The percentage inhibition was calculated according to Kotyuk [11] .…”