Efficacy of a Si-based agent against developing renal failure in a rat remnant kidney model.

Abstract

Chronic renal failure is exacerbated by oxidative stress, and this condition is difficult to treat in advanced stages. Because of the lack of effective treatments, the disease is a global public health concern. We developed a Si-based agent that continuously generates hydrogen for more than 24 h by reacting with water under conditions similar to those in the gastrointestinal tract. Given the efficacy of hydrogen in the treatment of conditions associated with oxidative stress, we examined whether the Si-based agent had beneficial effects on the development of renal failure. The Si-based agent was orally administered to rats that were developing renal failure. Rats underwent 5/6 nephrectomy to establish a remnant kidney model. Specifically, on day -7, rats underwent right 2/3 nephrectomy, followed by light nephrectomy on day 0. Starting on day -3, the rats were administered a control or Si-based agent-containing diet for 8 weeks. Compared with the findings in control rats, the Si-based agent greatly suppressed the increases of both serum creatinine and urinary protein levels. All analyzed parameters of oxidative stress were significantly suppressed in the Si-based agent groups. Histopathological examination illustrated that glomerular hypertrophy was suppressed by the treatment. Quantitative real-time reverse transcription-polymerase chain reaction revealed that sirtuin 1 and heme oxygenase-1 expression was increased in the Si-based agent groups, suggesting improved antioxidant activity and reduced hypoxia. In addition, caspase-3 and interleukin-6 expression was suppressed in the Si-based agent groups, indicating the alleviation of apoptosis and inflammation. In conclusion, oral administration of a Si-based agent resulted in renoprotective effects, presumably by suppressing oxidative stress via hydrogen generation.

• Authors: Ryoichi Imamura, Masataka Kawamura, Ayumu Taniguchi, Yuki Kobayashi, Shigeaki Nakazawa, Taigo Kato, Toyofumi Abe, Motohide Uemura, Hikaru Kobayashi, Norio Nonomura
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 533 Issue 4 Pg. 698-703 (12 17 2020) ISSN: 1090-2104 [Electronic] United States
• PMID: 33131768 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antioxidants
• Interleukin-6
• Hydrogen
• Creatinine
• Heme Oxygenase-1
• Caspase 3
• Sirtuin 1
• Silicon

Topics

• Administration, Oral
• Animals
• Antioxidants (pharmacology)
• Caspase 3 (genetics, metabolism)
• Cell Hypoxia
• Creatinine (blood)
• Disease Models, Animal
• Down-Regulation
• Heme Oxygenase-1 (genetics, metabolism)
• Hydrogen (pharmacology, therapeutic use)
• Interleukin-6 (genetics, metabolism)
• Kidney (cytology, drug effects, metabolism, pathology)
• Kidney Failure, Chronic (drug therapy, pathology)
• Male
• Nephrectomy
• Oxidative Stress (drug effects)
• Rats
• Rats, Sprague-Dawley
• Silicon (chemistry, pharmacology, therapeutic use)
• Sirtuin 1 (genetics, metabolism)
• Up-Regulation