Lysosomal cysteine proteases are mediators of cell death in macrophages following exposure to amorphous silica nanoparticles.

Increasing use of nanomaterials in everyday products such as cosmetics, medicines and food packaging is of grave concern given the lack of understanding with regards the impact such materials have on biological systems. The aim of this study is to examine cell death induced by cationic amorphous silica nanoparticles and determine the involvement of lysosomal cysteine proteases in this process. We report that multiple forms of cell death including apoptosis and pyroptosis are elicited following exposure to amorphous silica nanoparticles and that lysosomal cysteine proteases are involved in both cell death pathways in macrophages. Interestingly, lysosomal cysteine protease mRNA expression and release into the extracellular environment is induced following exposure to amorphous silica nanoparticles. Previously, the determination of nanoparticle-induced toxicity has focused on cytokine readouts, but the work presented here demonstrates that changes to normal protease biology should also be considered when evaluating the molecular mechanisms by which nanoparticulate matter causes cellular inflammation and death.

Khaya senegalensis inhibits piroxicam mediated gastro-toxicity in wistar rats.

OBJECTIVE: The purpose of this study was to investigate the effects of piroxicam co-administration with ethanolic stem-bark extract of Khaya senegalensis on biomarkers of oxidative stress and gastro-toxicity in Wistar rats. MATERIALS AND METHODS: Thirty healthy male and female Albino Wistar rats (190-220 g) were grouped into six (n = 5) with designated treatments including: Normal saline, piroxicam (20 mg/kg), extract (200 and 400 mg/kg) alone and both doses of the extract co-administered with piroxicam. The drugs were administered orally to all the rats for fourteen consecutive days and on the fifteenth day, they were euthanized with chloroform inhalation. Blood samples and the stomachs were isolated for evaluation of the oxidative stress biomarkers and gastro integrity, respectively. RESULTS: The results of the study revealed that the levels of oxidative stress markers didn't differ significantly between the groups receiving the extract alone, the extract in combination or piroxicam alone. Gross and histological observations of the stomach showed gastric mucosal changes and mild atrophic lesions in the piroxicam group only. CONCLUSION: This study illustrates the interaction of Khaya senegalensis and piroxicam results in the gastro-protective beneficial effects. The extract's outcome on various prostaglandin levels and synthesis is being considered towards possible elucidation regarding the exact mechanism of cytoprotection.