Blueberry effects on prediabetic nephropathy—a preclinical in vivo approach

Abstract

Abstract Background Prediabetic Nephropathy (PreDN) therapeutic arsenal remains scarce. Blueberries (BB) display insulin sensitizing, lipid-lowering, antioxidant and anti-inflammatory effects. Therefore, we aimed to assess the putative benefits arising from BB supplementation in experimental PreDN. Methods BB polyphenol (PP) content was assessed by HPLC/PDA/ESI-MSn. Twenty-four male Wistar rats were divided in three groups (n = 8) for 24 weeks: Control group (Standard chow, Sd), 45% High-Fat (HF) diet-induced PreDN group and BJ-treated group (HF+BJ) [25 g/kg BW per day from week 16 onwards]. Glycemic/insulinemic/lipidic profiles were examined. Renal function was assessed by serum/urinary measures of creatinine, albumin, uric acid and glucose. Kidney histological characterization was performed by Periodic Acid-Shiff and Gomori’s green trichrome staining. Relative gene expression (RT-PCR) was also evaluated (KIM-1, NLRP3). Values are means ± S.E.M (ANOVA/post-hoc tests). This work was approved by the ORBEA of iCBR-FMUC (9/2018). Results HPLC/PDA/ESI-MSn analysis revealed that the main PP’s present in BB are malvidin derivatives, quercetin-O-hexoside and caffeic acid. HF animals displayed increased BW, glucose intolerance, postprandial hyperinsulinemia, elevated circulating LDL-c, hepatic/renal lipidosis, mild impairments in renal function and histological lesions resembling the stages I/II of PreDN. Apart from ameliorating prediabetic glucose intolerance, BJ supplementation elicited hepatic lipid accumulation and increased gene expression of renal inflammasome and KIM-1 without major improvements on renal function and/or histopathology. Conclusions Even though BB was able to ameliorate prediabetic glucose intolerance, the BB dosage employed herein (25 g/kg BW) elicited deleterious effects in the kidney only perceived at a sub-clinical level.