Effect of Regular Exercise on the Histochemical Changes of D-Galactose-Induced Oxidative Renal Injury in High-Fat Diet-Fed Rats

Abstract

Renal lipid accumulation exhibits slowly developing chronic kidney disease and is associated with increased oxidative stress. The impact of exercise on the obese- and oxidative stress-related renal disease is not well understood. The purpose of this study was to investigate whether a high-fat diet (HFD) would accelerate d-galactose-induced aging process in rat kidney and to examine the preventive effect of regular exercise on the obese- and oxidative stress-related renal disease. Oxidative stress was induced by an administration of d-galactose (100 mg/kg intraperitoneally injected) for 9 weeks, and d-galactose-treated rats were also fed with a high-fat diet (60% kcal as fat) for 9 weeks to induce obesity. We investigated the efficacy of regular exercise in reducing renal injury by analyzing Nε-carboxymethyllysine (CML), 8-hydroxygluanine (8-OHdG) and apoptosis. When rats were fed with a HFD for 9 weeks in d-galactose-treated rats, an increased CML accumulation, oxidative DNA damage and renal podocyte loss were observed in renal glomerular cells and tubular epithelial cells. However, the regular exercise restored all these renal changes in HFD plus d-galactose-treated rats. Our data suggested that long-term HFD may accelerate the deposition of lipoxidation adducts and oxidative renal injury in d-galactose-treated rats. The regular exercise protects against obese- and oxidative stress-related renal injury by inhibiting this lipoxidation burden.

Gemigliptin improves renal function and attenuates podocyte injury in mice with diabetic nephropathy

“…Immunostaining was conducted according to a previously described protocol (Park et al, 2013). For immunohistochemical analysis, the antibodies used were rabbit anti-8-OHdG (Santa Cruz Biotechnology, Santa Cruz, CA, USA), mouse anti-receptor for advanced glycation end product (anti-RAGE, Abcam, MA, USA), and mouse anti-integrin-linked kinase (anti-ILK, Santa Cruz Biotechnology).…”

“…To directly observe the apoptosis of renal podocytes, tissue sections were double stained with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and Wilms tumor antigen-1 (WT-1) according to a previously published procedure (Park et al, 2013). Briefly, the sections were first labeled using the DeadEnd TUNEL system (Promega, Madison, WI, USA) and FITCconjugated streptavidin (Santa Cruz Biotechnology).…”

“…Gemigliptin treatment significantly decreased nephrin excretion (P o0.01 vs. db/db mice). To more accurately determine the extent of podocyte loss, podocytes were probed with anti-WT-1 and anti-synaptopodin antibodies (Park et al, 2013), and the mean number of positive-stained cells in a particular glomerulus were determined. In db/db mice, the number of WT-1-positive or synaptopodin-positive cells (red and green, respectively) significantly decreased compared to that in db/ þ mice (Fig.…”

Overexpression of heart-type fatty acid binding protein enhances fatty acid-induced podocyte�injury

“…Reactive oxygen species (ROS) have critical roles in the development and progression of kidney damage (27). ORG and diabetic nephropathy are associated with the increase of proinflammatory cytokines due to increased ROS production (26).…”

“…ORG and diabetic nephropathy are associated with the increase of proinflammatory cytokines due to increased ROS production (26). Renal lipid accumulation exhibits slowly developing chronic kidney disease and is associated with increased oxidative stress (27). ROS attack guanine bases in the DNA easily and form 8-OHdG, which binds to thymidine rather than cytosine, based on which the levels of 8-OHdG is generally regarded as a biomarker of mutagenesis consequent to oxidative stress, and as a risk factor for numerous diseases including diabetes (28).…”