Inhaled Hydrogen Gas Therapy for Prevention of Lung Transplant-Induced Ischemia/Reperfusion Injury in Rats

Kawamura, Tomohiro; Huang, Chang‐Hung; Tochigi, Naobumi; Lee, Sungsoo; Shigemura, Norihisa; Billiar, Timothy R.; Okumura, Meinoshin; Nakao, Atsunori; Toyoda, Yoshiya

doi:10.1097/tp.0b013e3181fe1357

Cited by 124 publications

(58 citation statements)

References 44 publications

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“…Our laboratory has extensively explored the application of hydrogen for the treatment of various diseases (7,9,33), including acute lung injuries (15,23,24). Hydrogen is a selective radical scavenger for hydroxyl radicals and peroxynitrite (14,37), and this aspect of hydrogen's chemistry may explain its therapeutic effects.…”

Section: L651mentioning

confidence: 99%

“…Hydrogen may also act as a gaseous signaling molecule, similar to nitric oxide (19). Our laboratory has explored the application of inhaled hydrogen for acute lung injuries and found that treatment with inhaled hydrogen mitigates mechanical ventilation-induced lung injury (15) and transplant-induced lung ischemia-reperfusion injury (23,24). We discovered that inhaled hydrogen gas induces heme oxygenase (HO)-1 in the donor lungs before transplantation and leads to excellent preconditioning of lung allografts and improved transplant outcomes (23).…”

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confidence: 99%

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Hydrogen gas reduces hyperoxic lung injury via the Nrf2 pathway in vivo

Kawamura

Wakabayashi

Shigemura

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

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135

113

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lung injury is a major concern in critically ill patients who receive high concentrations of oxygen to treat lung diseases. Successful abrogation of hyperoxic lung injury would have a huge impact on respiratory and critical care medicine. Hydrogen can be administered as a therapeutic medical gas. We recently demonstrated that inhaled hydrogen reduced transplant-induced lung injury and induced heme oxygenase (HO)-1. To determine whether hydrogen could reduce hyperoxic lung injury and investigate the underlying mechanisms, we randomly assigned rats to four experimental groups and administered the following gas mixtures for 60 h: 98% oxygen (hyperoxia), 2% nitrogen; 98% oxygen (hyperoxia), 2% hydrogen; 98% balanced air (normoxia), 2% nitrogen; and 98% balanced air (normoxia), 2% hydrogen. We examined lung function by blood gas analysis, extent of lung injury, and expression of HO-1. We also investigated the role of NF-E2-related factor (Nrf) 2, which regulates HO-1 expression, by examining the expression of Nrf2-dependent genes and the ability of hydrogen to reduce hyperoxic lung injury in Nrf2-deficient mice. Hydrogen treatment during exposure to hyperoxia significantly improved blood oxygenation, reduced inflammatory events, and induced HO-1 expression. Hydrogen did not mitigate hyperoxic lung injury or induce HO-1 in Nrf2-deficient mice. These findings indicate that hydrogen gas can ameliorate hyperoxic lung injury through induction of Nrf2-dependent genes, such as HO-1. The findings suggest a potentially novel and applicable solution to hyperoxic lung injury and provide new insight into the molecular mechanisms and actions of hydrogen.

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Section: L651mentioning

confidence: 99%

mentioning

confidence: 99%

Hydrogen gas reduces hyperoxic lung injury via the Nrf2 pathway in vivo

Kawamura

Wakabayashi

Shigemura

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

Self Cite

135

113

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“…Recently, molecular hydrogen (H 2 ) has been shown to be a novel therapeutic antioxidant by reducing detrimental ROS [11,12,13,14,15,16,17,18]. Results of previous studies showed that inhalation of H 2 gas efficiently protected against organ damage such as ischemia-reperfusion injury in the brain [11,12], liver [13], heart [14] and lungs [15], as well as experimental sepsis [16,17] in rodents.…”

Section: Introductionmentioning

confidence: 99%

Inhalation of Hydrogen Gas Is Beneficial for Preventing Contrast-Induced Acute Kidney Injury in Rats

Homma

Yoshida²,

Yamashita³

et al. 2015

Nephron Exp Nephrol

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Background: The present study aimed at investigating the effect of a novel antioxidant, hydrogen (H₂) gas, on the severity of contrast-induced acute kidney injury (CIAKI) in a rat model. Methods: CIAKI was induced in rats by intravenous injection of a contrast medium, Ioversol, in addition to reagents inhibiting prostaglandin and nitric oxide synthesis. During the injection of these reagents, the rats inhaled H₂ gas or control gas. Results: One day after the injection, serum levels of urea nitrogen were significantly lower in H₂ gas-inhaling CIAKI rats (17.6 ± 2.3 mg/dl) than those in control gas-treated CIAKI rats (36.0 ± 7.3 mg/dl), although they both were elevated as compared to untreated rats (14.9 ± 0.9 mg/dl). Consistently, creatinine clearance in H₂ gas-treated CIAKI rats was higher than that in control gas-treated counterparts. Renal histological analysis revealed that the formation of proteinaceous casts and tubular necrosis was improved by H₂ gas inhalation. Mechanistic analyses showed that inhalation of H₂ gas significantly reduced renal cell apoptosis, expression of cleaved caspase 3, and expression of an oxidative stress marker, 8-hydroxydeoxyguanosine, in injured kidneys. Conclusion: Results suggest that H₂ gas inhalation is effective in ameliorating the severity of CIAKI in rats by reducing renal cell apoptosis and oxidative stress.

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“…Accumulating evidence suggests that hydrogen has medicinal properties (4)(5)(6)(7)(8)(9)(10)(11)19); however, the molecular mechanism has yet to be elucidated. Little is known about the potential role of hydrogen in femoral head necrosis.…”

Section: A B a B Discussionmentioning

confidence: 99%

“…A number of studies have reported promising results regarding the role of hydrogen in treating diseases in the brain (4,5), heart (6), liver (7), kidney (8), intestine (9), lung (10) and spinal cord (11). Hydrogen has a positive effect in inhibiting oxidative stress.…”

Section: Introductionmentioning

confidence: 99%

Hydrogen-rich saline attenuates steroid-associated femoral head necrosis through inhibition of oxidative stress in a rabbit model

Huang

Jiao

Yan

2015

Experimental and Therapeutic Medicine

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Abstract.A growing body of evidence suggests that hydrogen is a novel, selective antioxidant that exerts a protective effect against organ damage. The present study investigated the effect of hydrogen-rich saline on corticosteroid-induced necrosis of the femoral head in an animal model established using prednisolone. A total of 30 healthy, male, adult New Zealand white rabbits were randomly divided into two groups: Hydrogen-rich saline (treated with hydrogen-rich saline via intraperitoneal injection) and placebo (treated with normal saline). At the set time-points, the structure of the femoral head was examined using a microscope; the concentrations of glutathione (GSH), lipid peroxide (LPO), vascular endothelial growth factor (VEGF) and thrombomodulin (TM) in the plasma were measured and the microvessel density was quantified. The results showed that hydrogen-rich saline significantly decreased the levels of VEGF, TM and LPO and increased the GSH level in steroid-associated necrosis of the femoral head in the rabbit model. A significant increase in the microvessel density was observed in the hydrogen-rich saline group. Histopathological staining confirmed the results of the biochemical analysis. The present study demonstrates that hydrogen treatment may alleviate steroid-associated osteonecrosis by inhibiting oxidative stress. Hydrogen-rich saline may provide an alternative treatment for steroid-associated necrosis of the femoral head.

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Inhaled Hydrogen Gas Therapy for Prevention of Lung Transplant-Induced Ischemia/Reperfusion Injury in Rats

Abstract: Treatment of LTx recipients with inhaled hydrogen can prevent lung I/R injury and significantly improve the function of lung grafts after extended cold preservation, transplant, and reperfusion.

Cited by 124 publications

References 44 publications

Hydrogen gas reduces hyperoxic lung injury via the Nrf2 pathway in vivo

Hydrogen gas reduces hyperoxic lung injury via the Nrf2 pathway in vivo

Inhalation of Hydrogen Gas Is Beneficial for Preventing Contrast-Induced Acute Kidney Injury in Rats

Hydrogen-rich saline attenuates steroid-associated femoral head necrosis through inhibition of oxidative stress in a rabbit model

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