Protective mechanism of sulforaphane in Nrf2 and anti-lung injury in ARDS rabbits

Abstract

The effect of sulforaphane on nuclear factor erythroid 2-related factor 2 (Nrf2) and its protective mechanism for lung injury in rabbits with acute respiratory distress syndrome (ARDS) were investigated. Thirty rabbits were randomly divided into control (n=10), model (n=10) and experimental groups (n=10). Rabbits in model group and experimental group were treated with femoral venous injection of oleic acid to establish the ARDS model, while those in control group were injected with the same volume of normal saline. The experimental group received intravenous injection of sulforaphane. Twelve hours after modeling, the clinical manifestations and deaths of rabbits in each group were recorded and compared, including blood gas indexes, lung index (LI), alveolar damage coefficient, serum Nrf2 expression, as well as messenger ribonucleic acid (mRNA) and protein expression of Nrf2 in lung tissues. Pink frothy sputum and death were observed in rabbits in model group and experimental group, but the number of such cases in experimental group was smaller than that in the model group (p<0.05). Compared with those in control group, LI and IQA in model group and experimental group were increased, but LI and IQA in the experimental group were significantly decreased compared with those in the model group. Compared with those in the model group, the blood gas indexes (PaO2, PaCO2 and SaO2) in the experimental group were significantly increased (p<0.05). Nrf2 in serum and lung tissues of rabbits in experimental group was significantly increased compared with that in model group (p<0.05). Sulforaphane significantly inhibits ARDS in rabbits and plays a protective role in ARDS through upregulating Nrf2.

Can Activation of NRF2 Be a Strategy against COVID-19?

“…The high bioavailability of SFN and its stabilized α-cyclodextrin-encapsulated version sulforadex (SFX-01) makes it an excellent candidate for alleviating excessive anti-inflammatory responses and protecting the lungs. SFN has been found to be protective in animal models of respiratory disease, including an ARDS model in rabbits [ 78 ] and a hyperoxia-induced pulmonary injury model in mice [ 79 ]. It also limits RSV replication and virus-induced inflammation in the lungs of wild-type, but not NRF2-null, mice [ 80 ].…”

Natural product derived phytochemicals in managing acute lung injury by multiple mechanisms

“…Sulforaphane significantly prevented pulmonary damage induced by LPS through activating the Nrf2-ARE signaling pathway [ 407 ], protected against inhaled arsenic-induced ALI through activating the Nrf2-defense responses [ 408 ], ameliorated hyperoxia-induced ALI through regulating HMGB1 activity [ 409 ] as well as prevented chromium-induced pulmonary toxicity in rats through regulating the Nrf2-mediated Akt/GSK-3β/Fyn signaling pathway [ 410 ]. Moreover, sulforaphane also inhibited lung injury induced by oleic acid in rabbits through up-regulating the Nrf2 signaling pathway [ 411 ].…”

Role of Nrf2 and Its Activators in Respiratory Diseases

“…Similarly, vitexin and aucubin both mitigate inflammatory and oxidative injury along with the suppression of inflammatory signaling, such as NLRP3/NF- κ B, and the induction of Nrf2 in the LPS-induced ARDS model in wild-type but not Nrf2 knockdown mice/macrophages [98, 99]. The most well-recognized Nrf2 inducer, sulforaphane, also exerts protective effects on an ARDS murine model induced by LPS via inhibiting the increase of NF- κ B and activating the Nrf2 pathway and is also reported to alleviate lung injury in another oleic acid-induced ARDS model [100, 101]. Indeed, a large number of compounds have been reported to act in a similar manner that activates Nrf2 signaling in an LPS-challenged ARDS model, such as resveratrol, alpha-lipoic acid, ethyl gallate, cordycepin, and syringin [102–107].…”