Nephroprotective potential of syringic acid in experimental diabetic nephropathy: Focus on oxidative stress and autophagy.

BACKGROUND: Diabetic nephropathy (DN) is a chronic hyperglycemic manifestation of microvascular damage in the kidneys. Widespread research in this area suggests the involvement of perturbed redox homeostasis and autophagy in renal cells phrase- promote the progression of DN. MATERIALS AND METHODS: Reframed sentences-The present study investigates the pharmacological effect of Syringic acid (SYA), in streptozotocin (STZ, 55 mg/kg, i.p) induced diabetic nephropathy model and in high glucose (30 mM) challenged rat renal epithelial cells (NRK 52E) cells with a focus on oxidative stress and autophagy mechanisms. RESULTS: Both in vivo and in vitro experimental data revealed elevated oxidative stress markers along with compromised levels of nuclear factor erythroid 2-related factor 2 (Nrf2), a pivotal cellular redox-regulated transcription factor in renal cells upon glycemic stress. Elevated blood glucose also reduced the autophagy process as indicated by low expression of light chain (LC) 3-IIB in diabetic kidney and in NRK 52E cells subjected to excess glucose. SYA (25 and 50 mg/kg, p.o.) administration for 4 weeks to diabetic rats, Reframed sentence-preserved the renal function as evidenced by reduced serum creatinine levels as well as improved urine creatinine and urea levles as compared to non treated diabetic animals. At the molecular level, SYA improved renal expression of Nrf2 and autophagy-related proteins (Atg5, Atg3, and Atg7) in diabetic rats. Similarly, SYA (10 and 20 µM) co-treatment in high glucose-treated NRK 52E cells displayed increased levels of Nrf2 and autophagy induction. CONCLUSION: Results from this study signify the renoprotective effect of SYA and highlight the modulation of oxidative stress and autophagy mechanisms to mitigate diabetic kidney disease.

Mitochondrial remodelling-a vicious cycle in diabetic complications.

Diabetes mellitus (DM) is a chronic, metabolic condition characterized by excessive blood glucose that causes perturbations in physiological functioning of almost all the organs of human body. This devastating metabolic disease has its implications in cognitive decline, heart damage, renal, retinal and neuronal complications that severely affects quality of life and associated with decreased life expectancy. Mitochondria possess adaptive mechanisms to meet the cellular energy demand and combat cellular stress. In recent years mitochondrial homeostasis has been point of focus where several mechanisms regulating mitochondrial health and function are evaluated. Mitochondrial dynamics plays crucial role in maintaining healthy mitochondria in cell under physiological as well as stress condition. Mitochondrial dynamics and corresponding regulating mechanisms have been implicated in progression of metabolic disorders including diabetes and its complications. In current review we have discussed about role of mitochondrial dynamics under physiological and pathological conditions. Also, modulation of mitochondrial fission and fusion in diabetic complications are described. The available literature supports mitochondrial remodelling as reliable target for diabetic complications.