Effects of 21-aminosteroid U-74389G on acute otitis media in a guinea pig model.

Free radicals participate in the development of disease under inflammatory conditions. Lipid peroxides such as malondialdehyde are regarded as markers of cell membrane damage by oxidative stresses. Previous work from our laboratory has demonstrated that lipidperoxidation is increased in acute otitis media in guinea pigs, implicating a role for free radicals as contributors to inflammation. In this study we examined the effect of lazaroid U-74389G, a 21-aminosteroid, on acute otitis media in guinea pigs. Streptococcus pneumoniae organisms were inoculated into the right tympanic cavity; sterilized phosphate-buffered saline solution was injected into the left ear to serve as a control. The guinea pigs were given intraperitoneal injections of 40 mg/kg of a lazaroid compound or its vehicle every 12 hours. Middle ear mucosa was collected and used for assay. We quantified lipid peroxide by means of the methylene blue-hemoglobin method and by means of measurement of thiobarbituric acid reactive substance. Lazaroid significantly (p < 0.05) suppressed production of lipid hyproperoxide of the middle ear mucosa of the guinea pigs with acute otitis media for up to 24 hours. These results suggest that lazaroid may reduce lipoperoxidation in the middle ear at an early stage of acute otitis media.