Abstract

 
 
 
 Purpose: To investigate the protective role of syringaresinol in a rat model of diabetic nephropathy (DN).
 Methods: Streptozotocin was injected intraperitoneally into rats to establish the diabetic model. Streptozotocin-induced rats were orally administered syringaresinol, and pathological changes in kidneys were assessed using hematoxylin and eosin staining. Enzyme-linked immunosorbent assay (ELISA) was used to determine kidney injury indicators, 24-h urine proteins, blood urea nitrogen (BUN), and serum creatinine (SCR). Blood glucose was measured using a blood glucose meter, while levels of malonaldehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX) in kidney were also measured using ELISA.
 Results: Pathological changes in the kidneys were observed in rats post-streptozotocin treatment. Administration of syringaresinol reduced the lesion degree, with improved pathological morphology in kidney. Syringaresinol administration significantly attenuated streptozotocin-increased levels of BUN, SCR, 24-h urine protein, and blood glucose (p < 0.01). Streptozotocin-induced oxidative stress, shown by enhanced MDA level and reduced levels of SOD, CAT, and GSH-PX, was reversed in rat kidneys following syringaresinol administration. However, the expression levels of nuclear factor erythropoietin- 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) proteins decreased, while transforming growth factor-beta 1 (TGF-β1) and signal transducer and transcriptional modulator (Smad) 2/3/7 proteins increased in rats post-streptozotocin treatment. Syringaresinol administration reversed the effects of streptozotocin on protein expression of Nrf2, HO-1, TGF-β1, and Smad 2/3/7.
 Conclusion: Syringaresinol exerted a protective effect against DN through activation of Nrf2 and inactivation of TGF-β1/Smad pathways. Thus, the compound can potentially be developed for management of diabetic nephropathy.
 
 
 
Highlights
Diabetes is a metabolic disease that causes the blood sugar to rise above normal levels, and results in cardiovascular or renal complications [1]
Since syringaresinol has been shown to promote activation of Nuclear factor erythropoietin-2-related factor 2 (Nrf2) to alleviate oxidative stress in diabetic cardiomyopathy [5], the present study investigated whether Nrf2/heme oxygenase 1 (HO-1) was implicated in the protection against Diabetic nephropathy (DN) by syringaresinol
Administration of syringaresinol dosedependently reduced the indicators of impaired kidney function, including blood urea nitrogen (BUN) (Figure 2 A), serum creatinine (SCR) (Figure 2 B), and 24-h urine protein (Figure 2 C), demonstrating that syringaresinol mitigated the loss of renal function in diabetic rats
Summary
Diabetes is a metabolic disease that causes the blood sugar to rise above normal levels, and results in cardiovascular or renal complications [1]. UV radiation-induced oxidative stress and inflammatory responses in skin cells were suppressed by syringaresinol [4]. Syringaresinol alleviated oxidative stress and inflammatory responses to attenuate diabetic cardiomyopathy [5]. For the determination of MDA, SOD, CAT, and GSH-PX, renal tissues were homogenized in normal saline, and the supernatants were harvested after centrifugation at 1000 × g for 20 min. The protein concentration was measured with a bicinchoninic acid protein assay kit (Beyotime Institute of Biotechnology, Shanghai, China), and the levels of MDA, SOD, CAT, and GSH-PX were determined using commercial assay kits (Sigma-Aldrich). Renal tissues were lysed in Cell Lysis Buffer (Sigma-Aldrich), and the protein concentration was determined via the bicinchoninic acid protein assay kit. Following incubation with horseradish peroxidase-linked secondary antibody (1:5000; Cell Signaling Technology), target proteins were detected using the enhanced chemiluminescence detection kit (GE Healthcare, Chicago, IL, USA). Statistical differences were determined using Student’s t-test or one-way analysis of variance, with p < 0.05 considered statistically significant
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
