Please use this identifier to cite or link to this item:
Author(s): Dinis Oliveira, RJ
Sousa, C
Remiao, F
Duarte, JA
Ferreira, R
Sanchez S Navarro
Bastos, ML
Carvalho, F
Title: Sodium salicylate prevents paraquat-induced apoptosis in the rat lung
Issue Date: 2007
Abstract: The nonselective contact herbicide, paraquat (PQ), is a strong pneumotoxicant, especially due to its accumulation in the lung through a polyamine uptake system and to its capacity to induce redox cycling, leading to oxidative stress-related damage. In the present study, we aimed to investigate the occurrence of apoptotic events in the lungs of male Wistar rats, 24, 48, and 96 h after PQ exposure (25 mg/kg ip) as well as the putative healing effects provided by sodium salicylate [(NaSAL), 200 mg/kg ip] when administered 2 h after PQ. PQ exposure resulted in marked lung apoptosis, in a time-dependent manner, characterized by the "ladder-like" pattern of DNA observed through electrophoresis and by the presence of tenninal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL)-positive cells (TPC) as revealed by immunohistochemistry. The two main caspase cascades (the extrinsic receptor-mediated and the intrinsic mitochondria-mediated) and the expressions of p53 and activator protein-1 (AP-1) were also evaluated, to obtain an insight into apoptotic cellular signaling. PQ-exposed rats suffered a time-dependent increase of caspase-3 and caspase-8 and a decrease of caspase-1 activities in lungs compared to the control group. A marked mitochondrial dysfunction evidenced by cytochrome c (Cyt c) release was also observed as a consequence of PQ exposure. In addition, fluorescence electrophoretic mobility shift assay (JEMSA) revealed a transcriptional induction of the p53 and AP-1 transcription factors in a timedependent manner as a consequence of PQ exposure. NaSAL treatment resulted in the remission of the observed apoptotic signaling and consequently of lung apoptosis. Taken together, the present results showed that PQ activates several events involved in the apoplotic pathways, which might contribute to its lung toxicodynamics. NaSAL, a recently implemented antidote for PQ intoxications, proved to protect lungs from PQinduced apoptosis.
Subject: Medicina clínica
Clinical medicine
Scientific areas: Ciências médicas e da saúde::Medicina clínica
Medical and Health sciences::Clinical medicine
Document Type: Artigo em Revista Científica Internacional
Rights: restrictedAccess
Appears in Collections:FADEUP - Artigo em Revista Científica Internacional
FFUP - Artigo em Revista Científica Internacional
REIT - Artigo em Revista Científica Internacional

Files in This Item:
File Description SizeFormat 
  Restricted Access
1.72 MBAdobe PDF    Request a copy from the Author(s)

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.