Tetrahydrocurcumin Ameliorates Kidney Injury and High Systolic Blood Pressure in High-Fat Diet-Induced Type 2 Diabetic Mice

Figures

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  Fig. 1. Tetrahydrocurcumin (THU) prevents an increase in body weight and food intake in high-fat diet (HFD)-fed mice. C57BL/6J mice were fed a regular diet (RD) or HFD for 12 weeks, and THU (50 or 100 mg/kg/day) was intragastrically administered with HFD. Changes in body weight (A) and food intake (B) during the experimental period. aP<0.05 vs. RD+vehicle (Veh); bP<0.05 vs. HFD+Veh (n=8 to 10 per group); cP<0.05 vs. HFD+THU50.

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  Fig. 2. Tetrahydrocurcumin (THU) alleviates glucose intolerance, insulin resistance, and renal dysfunction in high-fat diet (HFD)-fed mice. Intraperitoneal injection (IP) glucose tolerance test (GTT) and IP insulin tolerance test (ITT) (A, C) at 10 weeks. Levels of area under curve (AUC) in GTT and ITT (B, D). Kidney weight differences among the four groups (E). Albumin-creatinine ratio (ACR) analysis in urine collected at 24 hours (F). Changes in the glomerular filtration rate (GFR) after THU administration (G). RD, regular diet; Veh, vehicle. aP<0.05 vs. RD+Veh; bP<0.05 vs. HFD+Veh; cP<0.05 vs. HFD+THU50 (n=8 to 10 per group).

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  Fig. 3. Tetrahydrocurcumin (THU) protects against glomerular hypertrophy in high-fat diet (HFD)-fed mice. Effect of THU on the enlarged glomeruli of HFD-fed mice. Hematoxylin and eosin staining of the kidneys of all experimental groups (A). Changes in glomerular area and glomerular volume by THU (C, D) (n=8 to 10 per group). Renal ultrastructure changes caused by THU in HFD (B). Quantitative transmission electron microscopy (TEM) data. The glomerular basement membrane (GBM) thickness (E), slit pore numbers (F), and foot process width of podocytes (G) were analyzed by TEM at 15,000× magnification (n=5 per group). RD, regular diet; Veh, vehicle. aP<0.05 vs. RD+Veh; bP<0.05 vs. HFD+Veh; cP<0.05 vs. HFD+THU50 (scale bar=50 μm).

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  Fig. 4. Tetrahydrocurcumin (THU) restores nephrin expression and decreases extracellular matrix accumulation in the diabetic glomeruli of high-fat diet (HFD)-fed mice. Renal nephrin (A), fibronectin (B), and collagen type IV (C) were subjected to immunohistochemical (IHC) staining. Panel (D) indicates the percentage of positively stained area of each protein in glomeruli. Original magnification was 400× (scale bar=50 μm). Nephrin, fibronectin, and type IV collagen expression were analyzed by Western blotting (E, F). All protein expression analyses using Western blotting were performed on samples of the renal cortex (n=8 to 10 per group). RD, regular diet; Veh, vehicle. aP<0.05 vs. RD+Veh; bP<0.05 vs. HFD+Veh; cP<0.05 vs. HFD+THU50.

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  Fig. 5. Tetrahydrocurcumin (THU) downregulates the expression of angiotensin-converting enzyme (ACE), angiotensin 1 receptor (AT1R), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4), and chemokine C-C motif ligand 2 (MCP-1) in the glomeruli of high-fat diet (HFD)-fed mice. (A, B, C, D) ACE, AT1R, NADPH oxidase 4, and MCP-1 expression indicated by immunohistochemical staining. (E) Panel indicates the positively stained area of each protein in the glomeruli (n=4 to 5 per group; scale bar=50 μm). (F) Western blot analysis of the renal cortex. RD, regular diet; Veh, vehicle. aP<0.05 vs. RD+Veh; bP<0.05 vs. HFD+Veh; cP<0.05 vs. HFD+THU50.

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  Fig. 6. Tetrahydrocurcumin (THU) attenuates high systolic blood pressure and remodeling of vascular structures in high-fat diet (HFD)-fed mice. Vascular structural changes (A), nucleus count by tunica media area (μm2), vascular wall thickening (μm), vascular cross-sectional area (CSA) (×103 μm2) (B, C, D), systolic blood pressure (E), and heart rate throughout the 12 weeks of treatment (F) (n=8 to 10 per group). RD, regular diet; Veh, vehicle. aP<0.05 vs. RD+Veh; bP<0.05 vs. HFD+Veh; cP<0.05 vs. HFD+THU50.