Quercetin nanoparticles protect against prenatal tramadol-induced lung injury and pulmonary barrier affection in rat’s offspring via alleviation of oxidative stress, TNF‑α/NF‑κB signaling, apoptosis and fibrosis

Tramadol (T) is a widely used treatment for pain and has recently spread as non-medical abuse. Prenatal tramadol exposure (PTE) has a negative effect on fetal growth and pulmonary outcomes in offspring. Quercetin is a natural antioxidant, reduces inflammation, and prevents mutagenesis. This study aimed to investigate the ameliorating effects of quercetin nanoparticles (Q) against PTE-induced lung injury. Pregnant rats were divided into three groups: Control, T, and T+Q groups. Offspring of each group were subdivided into two subgroups; one sacrificed on post-natal day 7 and the other on post-natal day 60. Tramadol at both time points caused a significant increase in pulmonary malondialdehyde and NF-κB and a significant decrease in TAC, occludin, and ZO-1 protein levels. Histopathological changes were obvious in the lung tissues at both points, with a significant increase in collagen deposition, α-SMA, active caspase-3, and TNf-α immune-expression. Quercetin nanoparticle administration revealed a significant decrease in pulmonary malondialdehyde and NF-κB and a significant increase in TAC, occludin, and ZO-1 proteins. It also caused a significant improvement in the pulmonary histopathological changes, a significant decrease in collagen deposition, α-SMA, active caspase-3 expression, and TNF-α immune-reaction. In conclusion, quercetin nanoparticles showed ameliorative effects against lung injury induced by PTE via modulation of oxidative stress, NF-κB/TNF-α signaling, α-SMA-mediated fibrotic remodeling and apoptosis, with enhancement of pulmonary tight junction occludin and ZO-1 proteins.