2017 · Xing — Hydrogen Rich Water Attenuates Renal Injury and Fibrosis by Regulation of TGF-β-Induced Sirt1
Super-Abstract
Hydrogen-rich water reduced kidney fibrosis and dysfunction in a mouse model and prevented a critical cellular process — the transition of kidney epithelial cells into fibroblast-like cells — in human cell culture. The protective mechanism appears to run through Sirt1, a protein that hydrogen-rich water prevents TGF-β from suppressing. This is a preclinical animal and cell study; findings have not yet been tested in humans.
Commentary
Kidney fibrosis — the progressive scarring of the kidney — is a common endpoint of many chronic kidney diseases and ultimately leads to kidney failure. TGF-β1 is one of the key drivers of this process, partly by suppressing the protective protein Sirt1. This study used two complementary models: a mouse model of obstructive kidney damage (UUO) and human kidney tubular cells (HK-2) treated with TGF-β1. Hydrogen-rich water, given as drinking water to mice and as pretreatment to cells, reduced fibrosis markers, preserved kidney function parameters (creatinine, BUN), and — crucially — kept Sirt1 levels elevated. When the researchers blocked Sirt1 pharmacologically with sirtinol, hydrogen-rich water lost its protective effect, confirming Sirt1 as the key mediator. The study is technically sound for a preclinical paper, with multiple outcome measures and a mechanistic knockdown experiment. The main limitation is the large gap from mouse/cell results to any clinical application in human kidney disease.
Key quotes
- „HW can inhibit the development of fibrosis in kidney and prevents HK-2 cells from undergoing EMT which is mediated through Sirt1, a downstream molecule of TGF-β1.“ — the central mechanistic finding linking H₂ to Sirt1 protection
- „Sirtinol, a Sirt1 inhibitor, reversed the effect of HW on EMT induced by TGF-β1.“ — causal confirmation: blocking Sirt1 removes the H₂ benefit
- „The treatment with HW attenuated the development of fibrosis and deterioration of renal function in UUO model.“ — functional outcome in the animal model
Our assessment
This is a preclinical animal and cell study — findings cannot be directly transferred to humans. The mechanistic chain (H₂ → Sirt1 preservation → reduced EMT and fibrosis) is internally consistent and supported by the pharmacological knockdown experiment. However, the UUO model is a surgical obstruction model, not a model of the gradual chronic kidney disease typical in humans. Human HK-2 cells are a cell-line model with limited representativeness. No dosing guidance for humans can be derived from this study. The results are interesting as mechanistic groundwork, but clinical relevance remains unproven.
Study design
- Type: animal experiment + in-vitro study · Model: Balb/c mice (UUO renal fibrosis model) + human HK-2 kidney proximal tubular cells · H₂ delivery: hydrogen-rich water (drinking water for mice; pretreatment for cells)
- Outcome: reduced serum creatinine and BUN; reduced α-SMA and fibronectin (fibrosis markers); preserved E-cadherin; maintained Sirt1 expression; effect abolished by Sirt1 inhibitor sirtinol
Abstract
The current research was designed to study the role of hydrogen in renal fibrosis and the renal epithelial to mesenchymal transition (EMT) induced by transforming growth factor-β1 (TGF-β1). Hydrogen rich water (HW) was used to treat animal and cell models. Unilateral ureteral obstruction (UUO) was performed on Balb/c mice to create a model of renal fibrosis. Human kidney proximal tubular epithelial cells (HK-2 cells) were treated with TGF-β1 for 36 h to induce EMT. Serum creatinine (Scr) and blood urea nitrogen (BUN) were measured to test renal function, in addition, kidney histology and immunohistochemical staining of alpha-smooth muscle actin (α-SMA) positive cells was performed to examine the morphological changes. The treatment with UUO induced a robust fibrosis of renal interstitium, shrink of glomerulus and partial fracture of basement membrane. Renal function was also impaired in the experimental group with UUO, with an increase of Scr and BUN in serum. After that, Western-blot was performed to examine the expression of α-SMA, fibronectin, E-cadherin, Smad2 and Sirtuin-1 (Sirt1). The treatment with HW attenuated the development of fibrosis and deterioration of renal function in UUO model. In HK-2 cells, the pretreatment of HW abolished EMT induced by TGF-β1. The down-regulation the expression of Sirt1 induced by TGF-β1 which was dampened by the treatment with HW. Sirtinol, a Sirt1 inhibitor, reversed the effect of HW on EMT induced by TGF-β1. HW can inhibit the development of fibrosis in kidney and prevents HK-2 cells from undergoing EMT which is mediated through Sirt1, a downstream molecule of TGF-β1.
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