Protective effects of a hydrogen-rich solution during cold ischemia in rat lung transplantation

Saito, Masao; Chen‐Yoshikawa, Toyofumi F.; Takahashi, Mamoru; Kayawake, Hidenao; Yokoyama, Yuka; Kurokawa, Ryōsuke; Hirano, Shin‐ichi; Date, Hiroshi

doi:10.1016/j.jtcvs.2019.09.175

Cited by 21 publications

(26 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, HMGB1 can activate production reactive oxygen species and induce oxidative stress [ 20 , 21 ]. Oxidative stress tends to trigger the accumulation of excess inflammatory factors, which leads to a cascade of inflammatory responses, resulting in severe lung tissue damage [ 22 , 23 ]. Therefore, preconditioning with rHMGB1 to protect the lung against oxidative stress could be feasible technique to reduce the effects of LIRI.…”

Section: Introductionmentioning

confidence: 99%

Preconditioning with rHMGB1 ameliorates lung ischemia–reperfusion injury by inhibiting alveolar macrophage pyroptosis via the Keap1/Nrf2/HO-1 signaling pathway

et al. 2020

View full text Add to dashboard Cite

Background: Lung ischemia-reperfusion injury (LIRI) is a complex pathophysiological process that can lead to poor patient outcomes. Inflammasome-dependent macrophage pyroptosis contributes to organ damage caused by ischemia/reperfusion injury. Oxidative stress and antioxidant enzymes also play an important role in LIRI. In this study, we conducted experiments to investigate whether and how preconditioning with rHMGB1 could ameliorate LIRI in a mouse model. Methods: Adult male BALB/c mice were anesthetized, the left hilus pulmonis was clamped, and reperfusion was performed. rHMGB1 was administered via intraperitoneal injection before anesthesia, and brusatol was given intraperitoneally every other day before surgery. We measured pathohistological lung tissue damage, wet/dry mass ratios of pulmonary tissue, and levels of inflammatory mediators to assess the extent of lung injury. Alveolar macrophage pyroptosis was evaluated by measuring release of lactate dehydrogenase, caspase-1 expression was assessed using flow cytometry, and gasdermin-D expression was analyzed using immunofluorescent staining. Levels of oxidative stress markers and antioxidant enzymes were also analyzed. Results: Preconditioning with rHMGB1 significantly ameliorated lung injury induced by ischemia-reperfusion, based on measurements of morphology, wet/dry mass ratios, as well as expression of IL-1β, IL-6, NF-κB, and HMGB1 in lung tissues. It also alleviated alveolar macrophage pyroptosis, reduced oxidative stress and restored the activity of antioxidant enzymes. These beneficial effects were mediated at least in part by the Keap1/Nrf2/HO-1 pathway, since they were reversed by the pathway inhibitor brusatol. Conclusions: Preconditioning with rHMGB1 may protect against LIRI by suppressing alveolar macrophage pyroptosis. This appears to involve reduction of oxidative stress and promotion of antioxidant enzyme activity via the Keap1/ Nrf2/HO-1 pathway.

show abstract

Section: Introductionmentioning

confidence: 99%

Preconditioning with rHMGB1 ameliorates lung ischemia–reperfusion injury by inhibiting alveolar macrophage pyroptosis via the Keap1/Nrf2/HO-1 signaling pathway

et al. 2020

View full text Add to dashboard Cite

show abstract

“…In the case of ischemic organ transplantation, rejection is strongly associated with microcirculatory changes induced by inflammatory cytokines due to IRI ( 44 , 45 ). Hydrogen has been shown to suppress the production of the major inflammatory cytokines IL-1β, IL-6, and TNF-α, and it has anti-inflammatory effects that reduce tissue damage ( 29 , 34 ). Saito et al reported that using hydrogenated preservatives for lung transplantation reduced the expression of IL-1β and 8-hydroxyguanosine and reduced the number of neutrophils attached to the vascular wall and hydrogen-inhibited vascular endothelial damage ( 29 ).…”

Section: Discussionmentioning

confidence: 99%

“…The anti-inflammatory effects of hydrogen, such as inhibiting inflammatory cytokines, inducing HO-1, and activating NF-E2-related factor, have been reported in transplanted organs ( 27 , 28 ). This solution has been shown to be effective in suppressing IRI in transplanted organs such as the heart, lung, and kidney ( 29 – 34 ). In the present study, we aimed to verify the impact of hydrogen gas treatment in the prevention of chronic rejection of marginal kidney graft with an optimal immunosuppressive protocol based on human clinical setting by using the miniature pig model.…”

Section: Introductionmentioning

confidence: 99%

Prevention of Chronic Rejection of Marginal Kidney Graft by Using a Hydrogen Gas-Containing Preservation Solution and Adequate Immunosuppression in a Miniature Pig Model

et al. 2021

View full text Add to dashboard Cite

In clinical kidney transplantation, the marginal kidney donors are known to develop chronic allograft rejection more frequently than living kidney donors. In our previous study, we have reported that the hydrogen gas-containing organ preservation solution prevented the development of acute injuries in the kidney of the donor after cardiac death by using preclinical miniature pig model. In the present study, we verified the impact of hydrogen gas treatment in transplantation with the optimal immunosuppressive protocol based on human clinical setting by using the miniature pig model. Marginal kidney processed by hydrogen gas-containing preservation solution has been engrafted for long-term (longer than 100 days). A few cases showed chronic rejection reaction; however, most were found to be free of chronic rejection such as graft tissue fibrosis or renal vasculitis. We concluded that marginal kidney graft from donor after cardiac death is an acceptable model for chronic rejection and that if the transplantation is carried out using a strict immunosuppressive protocol, chronic rejection may be alleviated even with the marginal kidney.

show abstract

“…In addition, HMGB1 has the function of activating reactive oxygen species and induce oxidative stress [20][21]. Oxidative stress triggers subsequent excess inflammatory factors accumulation and cascades of inflammatory response, thus resulting in severe lung tissue damage [22][23]. Therefore, preconditioning with rHMGB1 to protect the lung against oxidative stress might be an feasible method for ameliorating LIRI.…”

Section: Introductionmentioning

confidence: 99%

Preconditioning with rHMGB1 ameliorates lung ischemia–reperfusion injury through inhibiting alveolar macrophages pyroptosis via Keap1/Nrf-2/HO-1 signal pathway

Lin

Jingyuan

Liang

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Lung ischemia-reperfusion injury (LIRI) is a common and complex pathophysiological process that can lead to poor patient outcomes. Inflammasome-dependent macrophage pyroptosis contributes to organ damage caused by ischemia-reperfusion (I/R). Oxidative stress reaction and antioxidant enzymes also play an important role in LIRI. This experiment was conducted to investigate whether preconditioning with rHMGB1 could ameliorate LIRI and explore the mechanisms of its protective effect in a lung I/R mice model. Methods Adult male mice were anesthetized and the left hilus pulmonis was clamped for 60 min, followed by 120 min of reperfusion. rHMGB1 was performed by intraperitoneal injection at 2 h before anesthesia. Brusatol (Nrf-2 antagonist) was given intraperitoneally every other day for a total of five times before surgery. Measurements of pathohistological lung tissue damage, pulmonary wet/dry (W/D) ratios, inflammatory mediators were performed to assess the extent of lung injury after I/R. Alveolar macrophages (AMs) pyroptosis were evaluated by LDH release, caspase-1 expression in flow cytometry, GSDMD expression in immunofluorescent staining. Measurement of the products of oxidative Stress (ROS, MDA, 15-F2t-Isoprostane) and the antioxidant enzymes (SOD, GSH-PX, CAT) were performed. Results Preconditioning with rHMGB1 significantly ameliorated I/R-induced lung injury through measuring the morphology, wet/dry weight ratio, the expressions of IL-1β, IL-6, NF-κB, HMGB1 in lung tissue. rHMGB1 preconditioning remarkably alleviated AMs pyroptosis induced by lung I/R. rHMGB1 preconditioning significantly reduced oxidative stress and restored the activity of antioxidative enzymes. In addition, rHMGB1 preconditioning mediated the activity of Keap1/Nrf-2/HO-1 pathway in LIRI. Furthermore, inhibiting Keap1/Nrf-2/HO-1 pathway through brusatol administration could aggravate lung tissue damage and inflammatory response after lung I/R. Also, brusatol administration could suppresse the antioxidant and anti-pyroptosis effects of rHMGB1 preconditioning in LIRI. Conclusions rHMGB1 preconditioning protects against LIRI through suppressing AMs pyroptosis. The mechanism is partially explained by inhibiting oxidative stress and improving the activity of antioxidative enzymes via Keap1/Nrf-2/HO-1 pathway.

show abstract

Protective effects of a hydrogen-rich solution during cold ischemia in rat lung transplantation

Cited by 21 publications

References 27 publications

Preconditioning with rHMGB1 ameliorates lung ischemia–reperfusion injury by inhibiting alveolar macrophage pyroptosis via the Keap1/Nrf2/HO-1 signaling pathway

Preconditioning with rHMGB1 ameliorates lung ischemia–reperfusion injury by inhibiting alveolar macrophage pyroptosis via the Keap1/Nrf2/HO-1 signaling pathway

Prevention of Chronic Rejection of Marginal Kidney Graft by Using a Hydrogen Gas-Containing Preservation Solution and Adequate Immunosuppression in a Miniature Pig Model

Preconditioning with rHMGB1 ameliorates lung ischemia–reperfusion injury through inhibiting alveolar macrophages pyroptosis via Keap1/Nrf-2/HO-1 signal pathway

Contact Info

Product

Resources

About