RESUMO
Antibiotic-resistant bacterial strains and the consequent surge in infections caused by them have become major public health concerns. Silver nanoparticles (AgNPs) exhibit antibacterial properties and have wide applications in biomedical sciences. In this study, AgNPs were synthesized in the presence of antibiotics: Ceftazidime (Cft), Cefotaxime (Cef), Ceftriaxone (Cfx), and Cefepime (Cpm), along with the extract of Mentha longifolia. Mentha longifolia-based AgNPs were kept as the control for all experiments. The associated metabolites, structural properties, surface charges, and antibacterial activity of the AgNPs were also evaluated. Overall, a blue-shift of SPR peaks was observed for control AgNPs (λmax = 421 nm, 422 nm, 426 nm, and 406 nm for Cft-AgNPs, Cef-AgNPs, Cfx-AgNPs, and Cpm-AgNPs, respectively), compared to the control (λmax = 438 nm). Fourier-transform infrared spectroscopy showed that antibiotic-based AgNPs had distinct peaks that corresponded to the respective antibiotics, which were not observed in the control. XRD analysis showed that there were observed changes in crystallinity in antibiotic-based AgNPs compared to the control. TEM images revealed that all samples had spherical nanoparticles with different sizes and distributions compared to the control. The Zeta potential for extract-based AgNPs was - 33.6 mV, compared to -19.6 mV for Cft-AgNPs, -2 mV for Cef-AgNPs, -21.1 mV for Cfx-AgNPs, and - 24.2 mV for Cpm-AgNPs. The increase in the PDI value for antibiotic-based AgNPs also showed a highly polydisperse distribution. However, the antibiotic-AgNPs conjugates showed significantly higher activity against pathogenic bacteria. The addition of antibiotics to AgNPs brought significant changes in structural properties and antibacterial activities.
RESUMO
Lipopolysaccharide (LPS), also known as endotoxin, can trigger septic shock, a severe form of inflammation-mediated sepsis with a very high mortality rate. However, the precise mechanisms underlying this endotoxin remain to be defined and detoxification of LPS is yet to be established. Macrophages, a type of immune cells, initiate a key response responsible for the cascade of events leading to the surge in inflammatory cytokines and immunopathology of septic shock. This study was undertaken to determine whether the LPS-induced inflammation in macrophage cells could be ameliorated via CDDO-IM (2-cyano-3,12 dioxooleana-1,9 dien-28-oyl imidazoline), a novel triterpenoid compound. Data from this study show that gene expression levels of inflammatory cytokine genes such as interleukin-1 beta (IL-1ß), interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-α), and monocyte chemoattractant protein-1 (MCP-1) were considerably increased by treatment with LPS in macrophages differentiated from ML-1 monocytes. Interestingly, LPS-induced increase in expression of pro-inflammatory cytokine levels is reduced by CDDO-IM. In addition, endogenous upregulation of a series of antioxidant molecules by CDDO-IM provided protection against LPS-induced cytotoxicity in macrophages. LPS-mediated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) transcriptional activity was also noted to decrease upon treatment with CDDO-IM in macrophages suggesting the involvement of the NF-κB signaling. This study would contribute to improve our understanding of the detoxification of endotoxin LPS by the triterpenoid CDDO-IM.