Histopathologic assessment of effects of penicilline and montelukast sodium on middle ear mucosa in rats with experimental acute otitis media

During the pathogenesis of acute otitis media, viral and bacterial antigens induce emission of various inflammatory mediators by stimulating inflamatory cells. Being one of those mediators, the leukotrienes (LT) are found to be the major factors in the formation of edema and mucus as well as development of tuba Eustachii dysfunction.Montelukast sodium is a receptor antagonist of selective cystenyl leukotriene and exerts its effects through connecting to the receptor of cys LT1. In this study, an experiential acute supurative otitis media (ASOM) model was developed and responses of rats to penicilline and combinations of LT antagonist were compared with respect to histopathological observations conducted at both early and late phases.Fifty six Winstar rats were selected to be used in this study and a total of 83 ears having healthy tympanic membranes (TM) were included in the experiments as a result of otomicroscopic inspections applied to both ears of the selected rats. Transtympanical 0.03 ml of pneumococcus suspension was injected to all rats with the use of speculum under otomicroscopic control. Otomicroscopic inspection of all rats after a 48-hours time period revealed the development of pnomoccocal acute otitis media. Subjects were classified under four different groups having 14 rats at each.Intramusculer penicilline G (with a daily dose of 160,000 U/kg at a single shot) was given to rats in the first group for a period of five days. Animals in the second group were injected with a 10 mg/kg dose of intraperitoneal montelukast for 21 days in addition to a daily dose of 160,000 U/kg of intramuscular penicilline given at a single shot for a 5 days-period. Animals in the third group were injected with only an 10 mg/kg dose of intraperitoneal montelukast for 21 days. One cc of isotonic NaCl was given to the rats in the fourth group for a period of 21 days. For each study group, 7 randomly chosen animals were sacrificed at the 7th day of the experiment where the remaining 7 animals were sacrificed at the 21st day after otomicroscopic inspection. Temporal bones of the rats were dissected and histopathologically analyzed. Cross-sections were semi-quantitatively graded with respect to TM vascularization, TM inflammation, TM thickness, mucosal inflammation, mucosal thickness, mucosal vascularization and mucosal metaplasia.Results of the study indicated no significant differences between the groups, apart from mucosal vascularization with respect to mucosal and TM parameters at early phases. However, statistically significant differences were detected for the improvement of TM thickness with the help of penicillin treatment. Furthermore, considerable deviations were observed for the recuperation of TM and mucosal inflammation for groups where subjects were injected with montekulast as compared to other groups of the study.