Diphenyl pyrimidine exhibits protective effect on Staphylococcus aureus pneumonia in rat model by targeting NLRP3 expression

Abstract

Pneumonia is one of the most frequent disorder induced by S. aureus infection and accounts for 13.3% of the all the infections caused by staphylococcus. In the present study effect of diphenyl pyrimidine was investigated against Staphylococcus aureus (S. aureus) induced pneumonia in the rat model. The results demonstrated that diphenyl pyrimidine treatment of the rats effectively prevented S. aureus induced increase in mortality in dose-dependent manner. Diphenyl pyrimidine treatment inhibited histopathological changes in S. aureus infected rat lungs. Treatment of the rats with 1.25, 2.5, 5 and 10 mg/kg doses of diphenyl pyrimidine significantly (P < 0.05) reversed S. aureus infection induced increase in interleukin (IL)-1β, IL-18 and tumor necrosis factor (TNF)-α levels. Treatment with 1.25, 2.5, 5 and 10 mg/kg doses of diphenyl pyrimidine significantly (P < 0.05) reversed S. aureus infection induced increase nucleotide-binding domain and leucine-rich repeat containing (NLR) protein (NLRP3), apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC) and caspase-1 protein expression in rat lungs in dose-dependent manner. The NLRP3, ASC and caspase-1 mRNA level in S. aureus infected rat pulmonary tissues was significantly (P < 0.05) reduced by diphenyl pyrimidine treatment in dose-dependent manner. Thus, diphenyl pyrimidine protects S. aureus-induced pneumonia through suppression of NLRP3 and inflammatory cytokine expression. Therefore, diphenyl pyrimidine can be of therapeutic importance for the treatment of S. aureus induced pneumonia.