title: Substance P protects against hyperoxic-induced lung injury in neonatal rats.
abstract: The aim of the study was to investigate the effects of substance P (SP) in hyperoxia-induced lung injury in newborn rats. Thirty-two rat pups were randomly divided into four groups: normoxia/saline, normoxia/SP, hyperoxia/saline and hyperoxia/SP. In a separate set of experiments, the neonatal rat pups were exposed to 21% or >95% O2 for 14 days with or without intraperitoneal administration of SP. On day 14, the animals were sacrificed and the lungs were processed for histology and biochemical analysis. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was used for the detection of apoptosis. Antioxidant capacity was assessed by glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD), oxidative stress was assessed by determining the extent of formation of malondialdehyde (MDA), activities of NADPH oxidase activity, and formation of reactive oxygen species (ROS). The activity of phospho-p38 (p-p38) and -ERK1/2 (p-ERK1/2) proteins and expression of NF-E2-related factor 2 (NRF2) were detected by Western blot, and the expression of p-p38 was detected by immunofluorescence analysis. Compared with the hyperoxia treatment, the lung damage was significantly ameliorated following the SP treatment. Furthermore, the lungs from the pups exposed to hyperoxia TUNEL-positive nuclei increased markedly and decreased significantly after SP treatment. The levels of MDA decreased and that of GSH-Px and SOD increased following the SP treatment. The SP treatment significantly suppressed the activity of NADPH oxidase and reduced ROS production. SP stimulation may result in blocking p38 MAPK and ERK signaling pathways, and the activities of p-p38 and p-ERK, and expression of NRF2 decreased following the SP treatment. These findings indicate that SP can ameliorate hyperoxic lung injury through decreasing cell apoptosis, elevating antioxidant activities, and attenuating oxidative stress.
authors.affiliation: 1Pediatric Intensive Care Unit, The First People's Hospital of Zunyi , Zunyi , China.
authors.forename: Bo
authors.initials: B
authors.lastname: Huang
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Shuhong
authors.initials: S
authors.lastname: Xu
authors.forename: Mingyang
authors.initials: M
authors.lastname: Tian
authors.forename: Xinghui
authors.initials: X
authors.lastname: Zhen
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Bi
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001997:Bronchopulmonary Dysplasia / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D004353:Drug Evaluation, Preclinical; D004487:Edema / Q000209:etiology / Q000517:prevention & control; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D018496:Hyperoxia / Q000150:complications* / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D008315:Malondialdehyde / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011247:Pregnancy; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000494:pharmacology / Q000627:therapeutic use*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D051267:NF-E2-Related Factor 2; D018377:Neurotransmitter Agents; C495637:Nfe2l2 protein, rat; D013373:Substance P; D008315:Malondialdehyde; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Substance P; apoptosis; hyperoxic lung injury; oxidative stress