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Diabetes-induced renal failure is associated with tissue inflammation and neutrophil gelatinase-associated lipocalin: Effects of resveratrol

Koca Halit B. (Afyon Kocatepe University, Faculty of Medicine, Department of Medical Biochemistry, Afyonkarahisar, Turkey)
Pektas Mehmet B. (Afyon Kocatepe University, Faculty of Medicine, Department of Medical Pharmacology, Afyonkarahisar, Turkey)
Koca Selcen (Afyon Kocatepe University, Faculty of Medicine, Hospital Pharmacy, Afyonkarahisar, Turkey)
Pektas Gökhan (Elazığ Education and Research Hospital, Department of Hematology, Elazığ, Turkey)
Sadi Gökhan (Karamanoglu Mehmetbey University, K.Ö. Science Faculty, Department of Biology, Karaman, Turkey)

Diabetes mellitus is a chronic inflammatory disease characterized by high blood glucose levels due to the absence of secretion of insulin or its inefficient use in the body. In this study, we investigated how resveratrol administration affects the renal functions and pro-inflammatory signaling pathway components in streptozotocin-induced diabetes in male Wistar rats. Rats were randomly divided into four groups: (1) control/vehicle; (2) control/20 mg/kg resveratrol; (3) diabetic/vehicle; and (4) diabetic/20 mg/kg resveratrol. In addition to renal glucose, lipid, angiopoietin-1 (ANG-1), asymmetric dimethylarginine (ADMA), erythropoietin (EPO), malondialdehyde (MDA) and neutrophil gelatinase-associated lipocalin (NGAL) content, the gene expressions of pro-inflammatory markers, including inducible nitric oxide synthase (iNOS), nuclear factor kappa B (NF-κB), nuclear factor (erythroid-derived 2) like-2 (Nrf2), and the protein contents of interleukins-1β,6,8 (IL-1β,6,8) and tumor necrosis factor-α (TNF-α) were analyzed using qRT-PCR and ELISA, respectively. The rats in the diabetes group demonstrated significantly lower terminal body weight and renal ANG-1, but significantly higher renal glucose, cholesterol, triglyceride, ADMA and MDA concentrations. Diabetes triggered inflammation in kidney tissues, reflected as an increase in NGAL level. The renal inflammation observed in the diabetes group was associated with significant upregulation of components of the pro-inflammatory pathway, iNOS, NF-κB, Nrf2, IL-1β, IL-6, IL-8 and TNF-α. To some extent, resveratrol administration reversed the diabetes-induced changes in renal tissues, suggesting that resveratrol partially protected from diabetes-induced renal failure due to its restorative activities in tissue inflammation.

Keywords: diabetes, resveratrol, inflammation, kidney, NGAL