Ethanolic propolis extract attenuates thioacetamide-induced lung injury in rats through antioxidant, anti-apoptotic, anti-fibrotic effects and inhibition of NLRP3-mediated inflammation

Fuente: PubMed "propolis"
Tissue Cell. 2026 May 15;102:103556. doi: 10.1016/j.tice.2026.103556. Online ahead of print.ABSTRACTOBJECTIVE: This study aimed to evaluate the therapeutic effects of ethanolic propolis extract (PPL) against thioacetamide (ThA)-induced pulmonary injury in rats and elucidate the underlying mechanisms involving oxidative stress, inflammation, apoptosis, and the NF-κB/NLRP3 signaling pathway.METHODS: Twenty-four Male albino Wistar rats were randomly assigned to four groups (n = 6/group): control, PPL-only (500 mg/kg/day, oral), ThA-only (200 mg/kg, i.p., three times weekly), and ThA + PPL for 30 days. Lung tissue was analyzed for oxidative stress markers (GSH, SOD, CAT, MDA, NO), inflammatory cytokines (TNF-α, IL-1β), apoptotic proteins (Bax, Bcl-2), and NLRP3 gene expression by quantitative real-time PCR. Histopathological examination included Hematoxylin and eosin (H&E) staining for assessment of alveolar architecture, septal thickness, and inflammatory cell infiltration; Masson's trichrome staining for evaluation of collagen deposition and pulmonary fibrosis; and immunohistochemical staining for NF-κB and α-SMA expression, quantified as percentage of positive area.RESULTS: ThA administration induced severe pulmonary injury characterized by significant oxidative stress (GSH ↓64%, SOD ↓41%, CAT ↓55%, MDA ↑229%, NO ↑90%), elevated inflammatory cytokines (TNF-α ↑254%, IL-1β ↑178%), apoptotic dysregulation (Bax ↑62%, Bcl-2 ↓45%), upregulated NLRP3 expression (↑329%), and marked histopathological damage including increased inflammatory score (↑640%), septal thickening (↑151%), collagen deposition (↑143%), NF-κB expression (↑108%), and α-SMA expression (↑111%). PPL co-treatment significantly ameliorated these alterations, restoring antioxidant defenses (GSH ↑158%, SOD ↑38%, CAT ↑129%, MDA ↓47%, NO ↓39%), suppressing inflammation (TNF-α ↓52%, IL-1β ↓54%), rebalancing apoptosis (Bax ↓15%, Bcl-2 ↑58%), downregulating NLRP3 expression (↓52%), and improving histopathological parameters (inflammatory score ↓50%, septal thickness ↓42%, collagen deposition ↓45%, NF-κB ↓30%, α-SMA ↓44%) compared to the ThA group.CONCLUSION: Ethanolic propolis extract effectively attenuates ThA-induced lung injury in rats through multi-targeted mechanisms involving antioxidant defense restoration, anti-inflammatory activity, apoptosis modulation, and downregulation of the NF-κB/NLRP3 signaling pathway. These findings support its therapeutic potential as a natural agent against chemical-induced pulmonary toxicity.PMID:42160819 | DOI:10.1016/j.tice.2026.103556