Leukotriene antagonist and dexamethazone: effects on airway functional and pathological changes after chlorine inhalation in guinea pigs

ABSTRACT

In an animal model of guinea pigs, search for any adverse effects was made, by studying functional and pathological changes in pulmonary airways that may arise from inhalation of increasing concentration of chlorine gas as in swimming pools and how to ameliorate these effects by administration of leukotriene antagonist [Montelukast] or corticosteroids [Dexamethazone] separately or in combination. The different parameters assessed in the present study included specific airway resistance [sRaw], tidal volume of guinea pigs subjected to chlorine inhalation, air way reactivity to acetyl choline [PC100] and total cell count and differential count in bronchoalveolar lavage [BAL] 48 hrs and 21 days after exposure to chlorine inhalation. Guinea pigs were divided into five groups, one group served as control. The other four groups were subjected to chlorine inhalation, one group of them not receiving any medication, while the other three groups received medication starting from half hour after chlorine exposure and for 21 days, either with montelukast receiving daily intraperitoneal injection of a dose 10 mg/Kg or receiving corticosteroid [dexamethazone] daily intraperitoneal injection of a dose 20 mg/Kg, while the last group received the two medications combined together. On analysis of the results, there were highly significant changes and worsening of all parameters in the group subjected to chlorine inhalation without any medication, compared to control, either 48 hours or 21 days after chlorine inhalation [p<0.001]. The only exception is cell count in bronchoalveolar lavage [BAL] which showed insignificant changes [p>0.05] either in total cell or differential count 21 days after chlorine inhalation. The present study also demonstrated significant improvement [p<0.001] after administration of leukotriene antagonist [montelukast] starting half hour after chlorine inhalation and for 21 days. Also, there was significant improvement after treatment with corticosteroids [dexamethazone] [p<0.001]. The highest improvement was recorded in the group receiving both medications montelukast and dexamethazone combined together. However the results of the present study demonstrated that montelukast, although it produced marked improvement, yet it was the least effective in this respect, followed by dexamethazone and the best improvement was noticed when the two medications were combined together