Effects of hydrogen-rich water on abnormalities in a SHR.Cg-Leprcp/NDmcr rat - a metabolic syndrome rat model

Abstract

Background: Hydrogen (H2), a potent free radical scavenger, selectively reduces the hydroxyl radical, which is the most cytotoxic of the reactive oxygen species (ROS). An increase in oxygen free radicals induces oxidative stress, which is known to be involved in the development of metabolic syndrome. Therefore, we investigated whether hydrogen-rich water (HRW) affects metabolic abnormalities in the metabolic syndrome rat model, SHR.Cg-Leprcp/NDmcr (SHR-cp).

Methods: Male SHR-cp rats (5 weeks old) were divided into 2 groups: an HRW group was given oral HRW for 16 weeks, and a control group was given distilled water. At the end of the experiment, each rat was placed in a metabolic cage for 24 h, fasted for 12 h, and anesthetized; the blood and kidneys were then collected.

Results: Sixteen weeks after HRW administration, the water intake and urine flow measured in the metabolic cages were significantly higher in the HRW group than in the control group. The urinary ratio of albumin to creatinine was significantly lower and creatinine clearance was higher in the HRW group than in the control group. After the 12-h fast, plasma urea nitrogen and creatinine in the HRW group were significantly lower than in the control group. The plasma total antioxidant capacity was significantly higher in the HRW group than in the control group. The glomerulosclerosis score for the HRW group was significantly lower than in the control group, and a significantly positive correlation was observed between this score and plasma urea nitrogen levels.

Conclusion: The present findings suggest that HRW conferred significant benefits against abnormalities in the metabolic syndrome model rats, at least by preventing and ameliorating glomerulosclerosis and creatinine clearance.

Figure 1

Effect of HRW administration on body weight. White circle, distilled water-administered rats (control, n = 12); black circle, hydrogen-rich water-administered rats (HRW, n = 12). *P < 0.05.

Figure 2

Photomicrographs of coronal sections of the glomeruli from SHR-cp rats. (A) Control group. (B) HRW group. Periodic acid-Schiff (PAS) staining of the control group revealed glomerular damage, which was characterized by segmental glomerular sclerosis and the formation of synechiae by the attachment of parietal epithelial cells to the denuded glomerular basement membrane (PAS stain, original magnification ×400).

Figure 3

Effect of HRW administration on glomerular sclerosis. After 16 weeks of HRW administration, coronal sections of the renal tissue from distilled water-administered rats (control, n = 8) and HRW-administered rats (HRW, n = 7) were stained with PAS and examined by light microscopy in a blinded fashion (Figure 3A). Glomerulosclerosis was semi-quantitatively evaluated according to the criteria developed by Uehara et al. [10]. *P < 0.05. Data represent mean ± SE. Figure 3B illustrates the relationship between the glomerulosclerosis score and concentrations of blood urea nitrogen. White and black circles indicate control and HRW rats, respectively.