Hydrogen-rich saline ameliorates renal injury induced by unilateral ureteral obstruction in rats.

Hydrogen has been demonstrated to have effective protection against tissue injuries caused by oxidative stress, inflammation, and apoptosis. This study investigated the efficacy of hydrogen-rich saline (HS) on the prevention of renal injury induced by unilateral ureteric obstruction (UUO) in rats. Male Sprague-Dawley rats were divided randomly into 4 groups: sham group, UUO group, UUO+saline group, and UUO+HS group. UUO was induced by ligation of the left ureter. 5ml/kg HRSS or saline was administered beginning 1day after UUO and for 10days thereafter. Rats were killed at 10days after UUO. Left kidneys were excised immediately for the tissue histologic examinations and biochemical assays. Renal injury scores in the UUO group and the UUO+saline group were significantly higher compared with those in the sham group. However, administration of HS significantly reduced the injury score. Apoptosis index was significantly increased in UUO group and the UUO+saline group. HS treatment also reduced the apoptosis index. Interstitial fibrosis and macrophage infiltration were obvious in UUO kidneys. However, HS treatment significantly reduced the fibrosis and infiltration of macrophage in UUO kidneys. Significant increase in the MDA level and decrease in the SOD activity were observed in UUO group and the UUO+saline group. MDA level of UUO+HS group was significantly reduced. In addition, SOD activity of was significantly improved after treatment of HS. The data provide a biochemical and histologic basis for HS acting as a novel therapeutic strategy for preventing the renal injury induced by UUO.

Xu B ，Zhang YB ，Li ZZ ，Yang MW ，Wang S ，Jiang DP ... -  《-》

Exogenous hydrogen sulfide prevents kidney damage following unilateral ureteral obstruction.

To investigate the protective effects of exogenous hydrogen sulfide (H2 S) against unilateral ureteric obstruction (UUO) induced renal injury and explore the potential mechanisms involved. Rats were randomly divided into four groups: sham group, UUO group, UUO + saline group, and UUO + NaHS group. Rats were sacrificed on Day 10 after UUO. The tubulointerstitial injury, interstitial fibrosis, and the infiltrating of macrophages in the interstitium were assessed. Expression of TNF-α in kidney tissue was also measured. Oxidative stress was evaluated by detecting the level of MDA and SOD in renal tissues. Interstitial fibrosis and renal injury score were markedly increased on Day 10 after UUO. In contrast, administration of NaHS significantly reduced the injury score. In addition, the kidneys that were treated with NaHS exhibited minimal interstitial fibrosis. The number of ED1 positive cells in the interstitium and the level of TNF-α were significantly higher in UUO kidneys compared with that in sham group. NaHS treatment significantly attenuated infiltration of macrophages and the expression of TNF-α. Our findings showed a significant increase in MDA level and decrease in the SOD activity in the UUO group compared to the sham group. However, significant decrease in MDA level and increase in SOD activity were observed after treatment of NaHS. Our study demonstrates that NaHS protects against UUO-induced renal damage via attenuating fibrosis, oxidative stress, and inflammation. Therefore, H2 S may be useful as a potential candidate in the treatment of renal damage induced by obstruction. Neurourol. Urodynam. 33:538-543, 2014. © 2013 Wiley Periodicals, Inc.

Jiang D ，Zhang Y ，Yang M ，Wang S ，Jiang Z ，Li Z ... -  《-》

[Effects of reduced glutathione on contents of hydroxyproline and oxidation stress reaction in kidney of unilateral ureteral obstruction in rat].

Na Y ，Zhang XX ，Zhang XD ，Yuan HP ，Hu XL ，Zheng W ，Li G ... -  《-》

Ulinastatin attenuates renal interstitial inflammation and inhibits fibrosis progression in rats under unilateral ureteral obstruction.

Jiang GT ，Chen X ，Li D ，An HX ，Jiao JD ... -  《-》

Hydrogen-rich water reduced oxidative stress and renal fibrosis in rats with unilateral ureteral obstruction.

Congenital obstructive nephropathy (CKD) is commonly implicated in the pathophysiology of chronic kidney disease occurring in the pediatric and adolescent age groups and the release of reactive oxygen species contribute to the worsening of renal fibrosis. Molecular hydrogen (H2) protects against tissue injury by reducing oxidative stress. We evaluated the efficacy of oral H2-rich water (HW) intake in preventing unilateral ureteral obstruction (UUO)-induced renal injury in rats. Male Sprague-Dawley UUO or control rats were administered with distilled water (DW) or HW for 2 weeks post-surgery. Histopathological and immunohistochemical analyses of kidney samples were performed. Histological changes were not apparent in the sham-operated kidneys. However, UUO kidneys were found to have widened interstitial spaces and tubular dilatation. Compared with the UUO + DW group, HW administration attenuated tubulointerstitial injury and reduced interstitial fibrotic area, causing a substantial decline in the frequency of α-SMA-, ED-1-, and TGF-β1-positive cells in the UUO + HW group. The decrease in the klotho mRNA expression in the UUO + HW group was less pronounced than that in the UUO + DW group. Oral HW intake reduced oxidative stress and prevented interstitial fibrosis in UUO kidneys, potentially involving klotho in the underlying mechanism. Oral intake of hydrogen-rich water (HW) can reduce oxidative stress and suppress interstitial fibrosis in unilateral ureteral obstruction-induced renal injury in rats. This mechanism possibly involves klotho, which is known for its antiaging roles. The association between molecular hydrogen and klotho in renal fibrosis is well known; this is the first report on the association in a unilateral ureteral obstruction model. Drinking HW is a safe and convenient treatment for oxidative stress-induced pathologies, without side effects. As a prospect for future research, oral HW intake to treat oxidative stress may improve renal fibrosis in congenital obstructive nephropathy.

Mizutani A ，Endo A ，Saito M ，Hara T ，Nakagawa M ，Sakuraya K ，Murano Y ，Nishizaki N ，Hirano D ，Fujinaga S ，Ohtomo Y ，Shimizu T ... -  《-》