Unravelling the Inflammatory Processes in the Early Stages of Diabetic Nephropathy and the Potential Effect of (Ss)-DS-ONJ

Abstract

Inflammatory processes play a central role in the pathogenesis of diabetic nephropathy (DN) in the early stages of the disease. The authors demonstrate that the glycolipid mimetic (Ss)-DS-ONJ is able to abolish inflammation via the induction of autophagy flux and provokes the inhibition of inflammasome complex in ex vivo and in vitro models, using adult kidney explants from BB rats. The contribution of (Ss)-DS-ONJ to reducing inflammatory events is mediated by the inhibition of classical stress kinase pathways and the blocking of inflammasome complex activation. The (Ss)-DS-ONJ treatment is able to inhibit the epithelial-to-mesenchymal transition (EMT) progression, but only when the IL18 levels are reduced by the treatment. These findings suggest that (Ss)-DS-ONJ could be a novel, and multifactorial treatment for DN.

A selenoureido-iminoglycolipid transported by zeolitic-imidazolate framework nanoparticles: a novel antioxidant therapeutic approach

“…On the other hand, a major bottelneck common to all the sp 2 -IGLs is their low solubility in biological media and consequent limited bioavailability, which is most likely the reason why the full therapeutic potential of these compounds is still underexploited. Doses around 10–50 μM are required to observe a significant cellular response both in vitro , 18 ex vivo 19,20 and in vivo models. 13,21 This suggests that sp 2 -IGLs are not efficiently internalized into cells, either due to their inactivation (by aggregation/insolubilization) in the extracellular medium before reaching the cell interior or by the sluggish diffusion across the cell membrane.…”