Polydatin-loaded chitosan nanoparticles ameliorates early diabetic nephropathy by attenuating oxidative stress and inflammatory responses in streptozotocin-induced diabetic rat.

Abstract

In various developed countries, diabetic nephropathy (DN) is the principal cause of end-stage kidney disease and a main reason of injury and mortality in individuals with renal morbidity worldwide. Polydatin (POL) has been evaluated as a potential antioxidant, anti-inflammatory and a nephroprotective agent. In spite of this, the possible benefits and protective effects of POL on early diabetic nephropathy are not quite clarified. For the effective clearance from the body besides safe drug delivery, biodegradable nanoparticles have interesting attraction. This work was designed to evaluate the positive effect and possible mechanisms of Polydatin-loaded Chitosan-Nanoparticles (POL-NPs) on early DN in streptozotocin-induced diabetic rats. Followed the induction of diabetes, rats classified into four groups, diabetic control and diabetic rats treated daily and orally with; POL, Polydatin-loaded chitosan-Nanoparticles (POL-NPs), plus normal control rats. Our findings showed that diabetic group presented a significant high level of the blood glucose, blood glycosylated hemoglobin (HbA1c), serum insulin, renal function related parameters, renal Advanced glycation-end products (AGEs) and lipid peroxidation level compared to normal control rats, while serum albumin level and the activities of renal antioxidant enzymes were significantly decreased. Moreover, in the kidney of diabetic rat mRNA expression of nuclear factor-kappa B (NF-κB) and cyclooxygenase-2 (Cox-2) were up-regulated. Besides, increase in serum levels of pro-inflammatory cytokines (TNF-α, IL-6 and IL-18) and decrease in anti-inflammatory cytokine (IL-10). POL and POL-NPs supplementation were significantly attenuate the above-mention results and returned the normal equilibrium between pro- and anti-inflammatory cytokines. In conclusion, POL and POL-NPs have antidiabetic effect, suppresses oxidative stress and mitigates renal inflammation through inhibition of NF-κB in diabetic kidney in early progressive DN.