Effect of Benfotiamine in Podocyte Damage Induced by Peritoneal Dialysis Fluid

Abstract

Background: In peritoneal dialysis (PD), residual renal function (RRF) fundamentally contributes to improved quality of life and patient survival. High glucose and advanced glycation end-products (AGE) contribute locally to peritoneal and systemically to renal damage. Integrity of podocyte structure and function is of special importance to preserve RRF. Benfotiamine could counteract the glucose and AGE-mediated toxicity by blocking hyperglycemia-associated podocyte damage via the pentose-phosphate pathway.Methods: A human differentiated podocyte cell line was incubated with control solution (control), 2.5% glucose solution (glucose), and 2.5% peritoneal dialysis fluid (PDF) for 48 h either ±50 μM benfotiamine. Podocyte damage and potential benefit of benfotiamine were analyzed using immunofluorescence, western blot analysis, and a functional migration assay. For quantitation, a semiquantitative score was used.Results: When incubating podocytes with benfotiamine, glucose, and PDF-mediated damage was reduced, resulting in lower expression of AGE and intact podocin and ZO-1 localization. The reorganization of the actin cytoskeleton was restored in the presence of benfotiamine as functional podocyte motility reached control level. Decreased level of inflammation could be shown as well as reduced podocyte apoptosis.Conclusion: These data suggest that benfotiamine protects podocytes from glucose and PDF-mediated dysfunction and damage, in particular, with regard to cytoskeletal reorganization, motility, inflammation, and podocyte survival.

Thiamine and benfotiamine: Focus on their therapeutic potential

“…We found similar effect of benfotiamine on morphological changes in dendritic cells which also undergo enlargement of the cell body and reorganization of the actin cytoskeleton after LPS stimulation, however benfotiamine reversed these changes, returning them to control levels [ 86 ]. Muller-Krebs et al, also found that benfotiamine restores reorganization of actin cytoskeleton of podocytes that were exposed to high glucose concentrations [ 88 ]. Cytoskeleton reorganization in activation of microglia has been attributed to activation of MAPK signaling cascade, specifically ERK1/2, p38 and JNKs were found to be partly responsible for morphological activation of microglia [ 89 ].…”

Glycative Stress and Its Defense Machinery Glyoxalase 1 in Renal Pathogenesis

“…Benfotiamine activates transketolase and has antioxidative effects in diabetes. This drug is proven to protect tissue from high-glucose–induced cell damage via alleviation of AGE accumulation [ 79 , 80 , 81 ]. Pyridoxamine inhibits AGE formation in vitro [ 82 ], and inhibits albuminuria in streptozotocin-induced diabetic rats [ 83 ].…”

Quercetin attenuates the proliferation, inflammation, and oxidative stress of high glucose-induced human mesangial cells by regulating the miR-485-5p/YAP1 pathway

“…[2][3][4] Podocytes, a specialized epithelial cell in outer surfaces of glomerular capillaries, are implicated in the progression of DN. 5,6 High blood sugar often leads to podocyte apoptosis and increased urine protein. 7,8 Current treatments of DN has great limitations, and patients in terminal stage have impaired quality of life and high mortality rate.…”