Oral Administration of Si-Based Agent Attenuates Oxidative Stress and Ischemia-Reperfusion Injury in a Rat Model: A Novel Hydrogen Administration Method

Abstract

Organ ischemia-reperfusion injury (IRI), which is unavoidable in kidney transplantation, induces the formation of reactive oxygen species and causes organ damage. Although the efficacy of molecular hydrogen (H 2) in IRI has been reported, oral intake of H 2-rich water and inhalation of H 2 gas are still not widely used in clinical settings because of the lack of efficiency and difficulty in handling. We successfully generated large quantities of H 2 molecules by crushing silicon (Si) to nano-sized Si particles (nano-Si) which were allowed to react with water. The nano-Si or relatively large-sized Si particles (large-Si) were orally administered to rats with renal IRI. Animals were divided into four groups: sham, IRI, IRI + nano-Si, and IRI + large-Si. The levels of serum creatinine and urine protein were significantly decreased 72 h following IRI in rats that were administered nano-Si. The levels of oxidative stress marker, urinary 8-hydroxydeoxyguanosine were also significantly decreased with the nano-Si treatment. Transcriptome and gene ontology enrichment analyses showed that the oral nano-Si intake downregulated the biological processes related to oxidative stress, such as immune response, cytokine production, and extrinsic apoptotic signaling pathway. Alterations in the regulation of a subset of genes in the altered pathways were validated by quantitative polymerase chain reaction. Furthermore, immunohistochemical analysis demonstrated that the nano-Si treatment alleviated interstitial macrophage infiltration and tubular apoptosis, implicating the anti-inflammatory and anti-apoptotic effects of nano-Si. In conclusion, renal IRI was attenuated by the oral administration of nano-Si, which should be considered as a novel H 2 administration method.

Novel hydrogen‐producing Si‐based agent reduces oxidative stress, and improves sperm motility and in vitro fertilization rate in varicocoele

“…5,7 In our previous report, the blood hydrogen levels increased in normal rats that consumed an Sibased agent containing diet for one week. 7 Therefore, hydrogen may be effective as a minimally invasive varicocoele treatment.…”

“…Moreover, the efficacy of this Si‐based agent has been reported in a rat remnant kidney model, mouse Parkinson's disease model, and rat kidney ischemia‐reperfusion injury model, all of which demonstrated reduction in oxidative stress 5,7 . In our previous report, the blood hydrogen levels increased in normal rats that consumed an Si‐based agent containing diet for one week 7 . Therefore, hydrogen may be effective as a minimally invasive varicocoele treatment.…”

“…Meanwhile, ingestion of 1 g of a Si‐based agent produces approximately 400 mL of hydrogen gas in 24 h, equivalent to that contained in 22 L of saturated hydrogen water. Moreover, the efficacy of this Si‐based agent has been reported in a rat remnant kidney model, mouse Parkinson's disease model, and rat kidney ischemia‐reperfusion injury model, all of which demonstrated reduction in oxidative stress 5,7 . In our previous report, the blood hydrogen levels increased in normal rats that consumed an Si‐based agent containing diet for one week 7 .…”

Hydrogen: A Novel Treatment Strategy in Kidney Disease

“…In addition, 8-OHdG and malondialdehyde are main forms of DNA and lipid damage-induced ROS, respectively [43]. Given that H 2 molecules can mitigate IRI by selectively removing ROS that lead to oxidative damage to DNA, lipids, and proteins, Kawamura et al [43] evaluated OS by monitoring urinary 8-OHdG and serum malondialdehyde levels. 8-OHdG and malondialdehyde, which are peroxidation products of DNA and lipids, respectively, are widely used as OS markers [46][47][48].…”

Molecular hydrogen is a potential protective agent in the management of acute lung injury

“…The action of molecular hydrogen in the body is moderate and no side effects have been identified so far. It can be conveniently administered through various modes, including gas inhalation, hydrogen-rich saline (HRS) injection, hydrogen-rich water (HW), and as nanocrystals to achieve targeted delivery and controlled release (Kawamura et al 2020). A simple method of administering molecular hydrogen is inhalation using a ventilator circuit, face mask, or nasal cannula.…”