Exploration of therapeutic role of montelukast and dexamethasone combination against paraquat induced inhalational toxicity

Abstract

Objectives To explore the therapeutic role of a single dose combination of montelukast (MON) and dexamethasone (DXM) through intra-peritoneal route against paraquat (PQ)-intoxicated experimental Wistar rats. Methods In vivo the survival rate was investigated following the administration of both MON and DXM in PQ exposed rats. Lungs parameters including enhanced pause (Penh), tidal volume (TV) and breath per minute (BPM) were determined using the whole body plethysmograph (WBP). Further chest imaging and histopathological studies were conducted to evaluate the lungs injury. In vivo the antioxidant activity was carried out by determining the levels of catalase (SOD), superoxide dismutase (CAT) and glutathione peroxidase (GSH-Px). Lungs tissue concentration of different proinflammatory cytokines like IL-1β, IL-6, TGF-β1 and TNF-α was also determined. Finally, expression of NF-kB and p-NF-kB was investigated by western blot. Results Results of survival rate and levels of lungs parameters indicated therapeutic potential of combination treatment of MON and DXM. Protective activity on lungs was reflected in chest imaging and histopathological investigations. Moreover, combination treatment exhibited significant increased levels of all anti-oxidant parameters. Significant decrease in the levels of IL-1β; IL-6; TGF-β1 and TNF-α was also observed with the combination treatment of MON and DXM. Evidence of significant down regulation of NF-kB and phospho-NF-kB was also found with the combination treatment of MON and DXM. Conclusions Given the advantage of therapeutic synergism activity of MON and DXM, it may be used in the prophylaxis of PQ-intoxication following clinical trials.