Diflunisal attenuates acute inflammatory responses through inhibition of NF-κB signaling pathway in Staphylococcus aureus-induced mastitis of lactating mouse model

Abstract

The cure rate of Staphylococcus aureus mastitis by conventional antibiotic therapy is very poor. Diflunisal (DIF), a difluorophenol derivative of salicylic acid, is reported to have strong anti-bacterial and anti-inflammatory effects against S. aureus infection. The present study aimed to evaluate the potential therapeutic effect of DIF administration against S. aureus-induced mastitis in mouse model by assessing the bacterial load, inflammation and histopathological changes in mammary gland. Eighteen lactating Swiss albino mice were divided into four groups: uninfected control, S. aureus-induced mastitis model, antibiotic (ceftriaxone)-treatment and diflunisal (DIF)-treatment. In S. aureus-induced mastitis mice, markedly increased bacterial load, myeloperoxidase, NF-κB and nitric oxide (NO) levels and up regulations of IL-1β, NF-κB and TNF-α mRNA expressions in mammary tissues with severe necrosis, marked infiltration of neutrophils and fibrosis in histopathology were noticed. Intramammary administration of DIF in S. aureus-induced mastitis mice showed a significant reduction in bacterial load, myeloperoxidase, NF-κB and NO concentrations in mammary tissues. The DIF treatment also suppressed the inflammatory NF-κB signaling in the inflamed mammary tissues by downregulation of IL-1β, NF-κB and TNF-α mRNA expressions. Further, the histopathology of mammary tissues showed mild necrosis with mild inflammatory cells infiltration, few bacterial colonies, moderate fibrosis, and marked regenerative changes with near to normal histological architecture. The findings of the study provide the evidence of therapeutic potential of DIF in S. aureus-induced mastitis by promising antibacterial and anti-inflammatory activities along with ameliorative impact against the histopathological alterations in mammary tissues.

Keywords: Diflunisal; Inflammation; Mastitis; Mice; NF-κB; Staphylococcus aureus.