title: [Inhibition of pulmonary nuclear factor -ΚB and tumor necrosis factor -α expression by diallyl sulfide in rats with paraquat poisoning].
abstract: OBJECTIVE
  To investigate the mechanism of anti-inflammatory effect of diallyl sulfide (DAS) in protection against acute lung injury (ALI) in rats with paraquat poisoning.
  
  
  METHODS
  Eighty male Wistar rats were randomly divided into four groups, namely: control group, model group, dexamethasone (DXM) treatment group, and DAS treatment group, with 20 rats in each group. The model of paraquat poisoning was reproduced by single does of 70 mg/kg given by gavage, while the same volume of normal saline (NS) was given in same manner in control group. 100 mg/kg of DAS, the same volume of NS, or 1 mg/kg DXM injection were given respectively in DAS treatment group, model group, or DXM treatment group intraperitoneally after exposure to paraquat, once a day for 14 days. Five rats in each group were sacrificed at 1, 3, 7, 14 days, respectively. The inferior lobe of right lung was harvested, and the degree of lung injury was observed with hematoxylin and eosin (HE) staining under optical microscope; the upper lobe of right lung was used to determine the lung wet/dry weight (W/D) ratio and for evaluation of the degree of pulmonary edema. The expression of nuclear factor -ΚB (NF-ΚB) in the middle lobe of right lung was assessed with immunohistochemistry. The expression of tumor necrosis factor -α ( TNF-α ) mRNA in the left lung was determined with the reverse transcription-polymerase chain reaction (RT-PCR).
  
  
  RESULTS
  (1) The pulmonary structure in control group was found to be intact. However, in the model group there were progressive pathological changes in lung, including marked edema and thickening of alveolar walls, collapse of alveoli, infiltration of inflammatory cells, alveolar wall, and obvious bleeding in the local lung tissue, and formation of transparent membrane in alveolar space. Less infiltration of inflammatory cells and no obvious destruction were found in alveolar structure in the DAS and DXM treatment groups. (2) Lung W/D ratio: lung W/D ratio of model group was apparently higher than that in control group at every time point, and peaking on the 3rd day ( 6.15 ± 0.54 vs. 4.15 ± 2.10, P < 0.05 ), and the ratio of lung W/D of DAS and DXM treatment groups was obviously lower than that in model group at every time point, especially on the 3rd day (3.99 ± 1.26, 4.30 ± 0.70 vs. 6.15 ± 0.54, both P < 0.05), but there was no significant difference between DAS and DXM treatment groups in this regard. (3) The immunocytochemistry analysis revealed minimal NF-ΚBp65 expression in the cell nuclei of the control group, while extensive NF-ΚBp65 expression was found in model group. Minimal NF-ΚBp65 positive expression in the cytoplasm and even less positive expression in the nucleus was found in the DAS and DXM treatment groups, and integral A value was significantly lower in the DAS and DXM treatment groups than that of the model group, especially on the 3rd day [(17.98 ± 0.06 )× 10⁷, (18.53 ± 0.04) × 10⁷ vs. (28.85 ± 0.61) × 10⁷, both P < 0.01], but there was no significant difference between DAS and DXM treatment groups. (4) It was shown by RT-PCR that the expression of TNF-α mRNA in lung tissue of the model group was significantly higher than that in the control group on the 3rd day (gray value: 3.63 ± 0.62 vs. 0.51 ± 0.13, P < 0.05 ). The expression of TNF-α mRNA in lung tissue was significantly decreased in DAS and DXM treatment groups compared with model group ( gray value: 2.49 ± 0.57, 2.02 ± 0.26 vs. 3.63 ± 0.62, both P < 0.05 ), but there was no significant difference between DAS and DXM treated groups.
  
  
  CONCLUSIONS
  Treatment with an intraperitoneally injection of DAS is capable of attenuate the extent of PQ-induced ALI in rats by alleviating pulmonary edema, inhibiting the expression of NF-ΚB and TNF-α in lung tissue, and ameliorating pathological changes in lung tissue.
authors.affiliation: Department of Critical Care Medicine, Haikou Municipal Hospital, Haikou 570208, Hainan, China. Corresponding author: Song Wei, Department of Emergency, Hainan Provincial People's Hospital, Haikou 570311, Hainan, China, Email: swhn1212@aliyun.com.
authors.forename: Yufang
authors.initials: Y
authors.lastname: Cao
authors.forename: Jinghui
authors.initials: J
authors.lastname: Li
authors.forename: Zongxing
authors.initials: Z
authors.lastname: Ou
authors.forename: Zongbao
authors.initials: Z
authors.lastname: Yin
authors.forename: Xuxu
authors.initials: X
authors.lastname: Chen
authors.forename: Yanli
authors.initials: Y
authors.lastname: Han
authors.forename: Wei
authors.initials: W
authors.lastname: Song
mesh_terms: D055371:Acute Lung Injury; D000498:Allyl Compounds; D000818:Animals; D008168:Lung; D008297:Male; D016328:NF-kappa B; D010269:Paraquat / Q000633:toxicity*; D012333:RNA, Messenger; D051381:Rats; D017208:Rats, Wistar; D013440:Sulfides; D014409:Tumor Necrosis Factor-alpha
chemical_list: D000498:Allyl Compounds; D016328:NF-kappa B; D012333:RNA, Messenger; D013440:Sulfides; D014409:Tumor Necrosis Factor-alpha; C038491:allyl sulfide; D010269:Paraquat