Ameliorative impact of sacubitril/valsartan on paraquat-induced acute lung injury: role of Nrf2 and TLR4/NF-κB signaling pathway

Abstract Herbicides such as paraquat (PQ) are frequently utilized particularly in developing nations. The present research concentrated on the pulmonary lesions triggered by PQ and the beneficial effect of the angiotensin receptor neprilysin inhibitor (ARNI), sacubitril/valsartan, against such pulmonary damage. Five groups of rats were established: control, ARNI, PQ (10 mg/kg), ARNI 68 + PQ, and ARNI 34 + PQ. Following euthanasia, lungs were isolated and subjected to a histopathological test, and the ELISA technique was used to evaluate oxidative stress biomarkers, toll-like receptor 4 (TLR4), nuclear factor erythroid 2–related factor 2 (Nrf2), phosphatidylinositol-3-kinase (PI3K), phosphorylated protein kinase B (p-AKT), and inflammatory markers: nuclear factor kappa B p65 subunit (NF-κB p65), tumor necrosis factor α (TNFα), and interleukin 1beta (IL-1β). In conjunction with abnormally high levels of malondialdehyde (MDA) and inducible nitric oxide synthase (iNOS), the PQ group also displayed low levels of reduced glutathione (GSH) and total antioxidant capacity (TAC). Additionally, TLR4, PI3K, and p-AKT were significantly elevated together with unusually low level of Nrf2. Moreover, inflammatory biomarkers, NF-κB p65, TNFα, and IL-1β, were abnormally elevated. Meanwhile, ARNI-treated groups reversed all alterations precipitated by PQ in a dose-dependent manner. ARNI could mitigate pulmonary damage triggered by PQ via potential antioxidant anti-inflammatory qualities. Graphical Abstract