Abstract
Purpose: Acute kidney injury (AKI) is a prominent risk factor for the development of chronic kidney disease (CKD). To date, the related mechanism and effective therapy have not been rigorously explored. The present study aims to investigate the reno-protection of hydrogen-rich saline (HRS) against ischemia/reperfusion (IR)-induced AKI.Methods: Adult male C57 mice were randomly allocated into three groups: Sham, IR, IR+HRS. Renal IR injury model was generated via 35 min occlusion of bilateral kidney pedicles, and then, mice were administered with different treatments intraperitoneally in various groups. After 14- or 28-day treatment, mice were perfused and the kidneys were collected following reperfusion. Many proteins were detected by western blots, including renal fibrotic proteins [a-smooth muscle actin (a-SMA), collagen I (Col I)], Klotho, the methylation of Klotho, damage-regulated autophagy modulator (Beclin-1), and microtubule-associated protein light 3-II (LC3-II). Finally, the levels of serum blood urea nitrogen (BUN) and creatinine (Cr) were measured to investigate the renal function.Results: Histological data showed that the HRS treatment significantly decreased the fibrosis in renal tissues when compared with the IR group, and both of BUN and Cr were lower in the HRS group than IR group (8.9 ± 0.6 vs. 9.9 ± 0.1 mmol/l, 51 ± 6.5 vs. 60 ± 5.8 μmol/l) (P < 0.05). The expression of fibrotic markers, a-SMA and Col I, showed a robust increase in IR injury models than the Sham group, which was consistent with the result of Trichrome staining. However, the levels of a-SMA and Col I expression were sharply decreased in the IR+HRS group (P < 0.05). IR injury also enhanced LC3-II and Beclin-1 expression, but decreased Klotho level. The Klotho level was alleviated by HRS, but LC3-II and Beclin-1 were starkly enhanced in HRS group (P < 0.05).Conclusion: HRS showed a protective effect in the prevention of renal injury and could inhibit renal fibrosis after IR injury in mice. This role of HRS might be exerted via retaining Klotho expression and activating autophagy in the kidney.
Highlights
Acute kidney injury (AKI) causes high morbidity and mortality in acute phase, with mortality rates reaching 50% in intensive care units (Ali et al, 2007; Grams et al, 2011)
These findings suggested that hydrogen-rich saline (HRS) improves renal function in mice after IR injury
This study showed HRS is able to promote renal function recovery after IR injury in mice by increasing Klotho expression, activating autophagy and inhibiting renal fibrosis
Summary
Acute kidney injury (AKI) causes high morbidity and mortality in acute phase, with mortality rates reaching 50% in intensive care units (Ali et al, 2007; Grams et al, 2011). It is a prominent risk factor for the development of chronic kidney disease (CKD). Hydrogen has protective effects on the kidney after ischemic AKI in animal studies (Li et al, 2016), the underlying mechanism remains unexamined. H2 is a known antiinflammatory molecule in acute pancreatitis, and colon and liver inflammation (Cheng et al, 2014; Yemm et al, 2015; Han et al, 2016)
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