PMID- 26713331
OWN - NLM
STAT- MEDLINE
DCOM- 20161114
LR  - 20181113
IS  - 1432-1912 (Electronic)
IS  - 0028-1298 (Linking)
VI  - 389
IP  - 3
DP  - 2016 Mar
TI  - Febuxostat protects rats against lipopolysaccharide-induced lung inflammation in 
      a dose-dependent manner.
PG  - 269-78
LID - 10.1007/s00210-015-1202-6 [doi]
AB  - The aim of the present work was to investigate possible protective effects of 
      febuxostat, a highly potent xanthine oxidase inhibitor, against acute lung injury 
      (ALI) induced by lipopolysaccharide (LPS) in rats. Male Sprague Dawley rats were 
      randomly divided into six groups, as follows: (i) vehicle control group; (ii) and 
      (iii) febuxostat 10 and febuxostat 15 groups, drug-treated controls; (iv) LPS 
      group, receiving an intraperitoneal injection of LPS (7.5 mg/kg); (v) and (vi) 
      febuxostat 10-LPS and febuxostat 15-LPS groups, receiving oral treatment of 
      febuxostat (10 and 15 mg/kg/day, respectively) for 7 days before LPS. After 18 h 
      administration of LPS, blood was collected for C-reactive protein (CRP) 
      measurement. Bronchoalveolar lavage fluid (BALF) was examined for leukocyte 
      infiltration, lactate dehydrogenase (LDH) activity, protein content, and total 
      nitrate/nitrite. Lung weight gain was determined, and lung tissue homogenate was 
      prepared and evaluated for oxidative stress. Tumor necrosis factor-alpha (TNF-alpha) was 
      assessed in BALF and lung homogenate. Moreover, histological changes of lung 
      tissues were evaluated. LPS elicited lung injury characterized by increased lung 
      water content (by 1.2 fold), leukocyte infiltration (by 13 fold), inflammation 
      and oxidative stress (indicated by increased malondialdehyde (MDA), by 3.4 fold), 
      and reduced superoxide dismutase (SOD) activity (by 34 %). Febuxostat 
      dose-dependently decreased LPS-induced lung edema and elevations in BALF protein 
      content, infiltration of leukocytes, and LDH activity. Moreover, the elevated 
      levels of TNF-alpha in BALF and lung tissue of LPS-treated rats were attenuated by 
      febuxostat pretreatment. Febuxostat also displayed a potent antioxidant activity 
      by decreasing lung tissue levels of MDA and enhancing SOD activity. Histological 
      analysis of lung tissue further demonstrated that febuxostat dose-dependently 
      reversed LPS-induced histopathological changes. These findings demonstrate a 
      significant dose-dependent protection by febuxostat against LPS-induced lung 
      inflammation in rats.
FAU - Fahmi, Alaa N A
AU  - Fahmi AN
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura 
      University, Mansoura, 35516, Egypt.
FAU - Shehatou, George S G
AU  - Shehatou GS
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura 
      University, Mansoura, 35516, Egypt. georgeshehatou@gmail.com.
FAU - Shebl, Abdelhadi M
AU  - Shebl AM
AD  - Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura, 
      Egypt.
FAU - Salem, Hatem A
AU  - Salem HA
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura 
      University, Mansoura, 35516, Egypt.
LA  - eng
PT  - Journal Article
DEP - 20151228
PL  - Germany
TA  - Naunyn Schmiedebergs Arch Pharmacol
JT  - Naunyn-Schmiedeberg's archives of pharmacology
JID - 0326264
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 101V0R1N2E (Febuxostat)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 4Y8F71G49Q (Malondialdehyde)
RN  - 9007-41-4 (C-Reactive Protein)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 1.17.3.2 (Xanthine Oxidase)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - Acute Lung Injury/chemically induced/*drug therapy/immunology/pathology
MH  - Animals
MH  - Anti-Inflammatory Agents/pharmacology/*therapeutic use
MH  - Bronchoalveolar Lavage Fluid/cytology/immunology
MH  - C-Reactive Protein/analysis
MH  - Dose-Response Relationship, Drug
MH  - Febuxostat/pharmacology/*therapeutic use
MH  - Glutathione/metabolism
MH  - L-Lactate Dehydrogenase/metabolism
MH  - Leukocyte Count
MH  - Lipopolysaccharides
MH  - Lung/drug effects/immunology/metabolism/pathology
MH  - Male
MH  - Malondialdehyde/metabolism
MH  - Nitric Oxide/metabolism
MH  - Pulmonary Edema/chemically induced/*drug therapy/immunology/pathology
MH  - Rats, Sprague-Dawley
MH  - Superoxide Dismutase/metabolism
MH  - Tumor Necrosis Factor-alpha/immunology
MH  - Xanthine Oxidase/antagonists & inhibitors
OTO - NOTNLM
OT  - Febuxostat
OT  - Inflammation
OT  - Lipopolysaccharide
OT  - Lung injury
OT  - Oxidative stress
OT  - TNF-alpha
EDAT- 2015/12/30 06:00
MHDA- 2016/11/15 06:00
CRDT- 2015/12/30 06:00
PHST- 2015/10/17 00:00 [received]
PHST- 2015/12/15 00:00 [accepted]
PHST- 2015/12/30 06:00 [entrez]
PHST- 2015/12/30 06:00 [pubmed]
PHST- 2016/11/15 06:00 [medline]
AID - 10.1007/s00210-015-1202-6 [pii]
AID - 10.1007/s00210-015-1202-6 [doi]
PST - ppublish
SO  - Naunyn Schmiedebergs Arch Pharmacol. 2016 Mar;389(3):269-78. doi: 
      10.1007/s00210-015-1202-6. Epub 2015 Dec 28.