Myrtenol-loaded niosomes can prevent lung ischemia-reperfusion injury model in rats by balancing the Nrf2/Keap1 and NF-κB signaling pathways.

Lung Ischemia-reperfusion injury (LIRI) is a risk during lung transplantation that can cause acute lung injury and organ failure. In LIRI, the NF-E2-related factor 2(Nrf2)/ Kelch-like ECH-associated protein 1 (Keap1) signaling pathway and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway are two major pathways involved in regulating oxidative stress and inflammation, respectively. Myrtenol, a natural compound with anti-inflammatory and antioxidant properties, has potential protective effects against IRI. This study aimed to explore the impact of myrtenol encapsulated within niosomes on the prevention of LIRI and examine the role of the two pathways mentioned in this process. Wistar rats were segregated into four groups. Animals received the myrtenol (MN) (32 mg/kg) or vehicle through daily inhalation for a week before LIRI. Expression of IκB, p-IκB, Nrf2, Keap1, Heme Oxygenase-1(HO-1), NF-κB signaling proteins, reactive oxygen species (ROS) level, caspase-3 expression, arterial blood gases, lung edema, and histopathological indices were assessed. Niosomal myrtenol significantly reduced lung edema, ROS, Keap1, p-IκB, NF-kB, Caspase-3, PaCO2 (the carbon dioxide pressure in arterial blood), and histopathological indices. Additionally, the expression of IκB, Nrf2, HO-1, and PaO2 (the oxygen pressure in arterial blood) increased significantly in the pretreated group compared to the IR group. Overall, inhalation of the niosomal myrtenol protects against lung ischemia-reperfusion injury, presumably through the balance between Nrf2/Keap1 and NF-κB pathways. The findings suggest that the niosomal form of myrtenol may be a potential candidate for developing new drugs to prevent and treat LIR damage.