Rho-kinase (ROCK-1 and ROCK-2) upregulation in oleic acid-induced lung injury and its restoration by Y-27632.
The possible contribution of Rho/Rho-kinase signalling in oleic acid (100 mg kg-1, i.v., for 4 h)-induced lung injury was investigated in rats. Furthermore, the possible protective effect of the administration of a Rho-kinase inhibitor, (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride monohydrate (Y-27632, 0.5-5 mg kg-1, i.v., 15 min before the administration of oleic acid), was also examined. Western blot analysis as well as histopathological examination revealed that Rho-kinase (ROCK-1 and ROCK-2) was upregulated in lungs obtained from oleic acid-administrated rats. In addition, the markers of oxidative and nitrosative stress, i.e., malondialdehyde, myeloperoxidase, 3-nitro-L-tyrosine and nitrite/nitrate, in serum and lung tissue were also increased in the injury group. Treatment of rats with 5 mg kg-1 Y-27632 reversed the oleic acid-induced lung damage, which was demonstrated by histopathological assessment and confirmed in Western blot experiments: ROCK-blots were more intense in the oleic acid group than in control and Y-27632 treatment reversed ROCK upregulation. In addition, malondialdehyde, myeloperoxidase, 3-nitro-L-tyrosine and nitrite/nitrate were also normalized after the administration of Y-27632 (0.5 mg kg-1 and 5 mg kg-1). These findings suggest that ROCK-1 and ROCK-2 are involved in oleic acid-induced lung damage in rats, and that inhibition of this enzyme by Y-27632 may have a protective effect against such damage. Consequently, Rho kinase inhibitors may be potential therapeutic agents in the treatment of acute respiratory distress syndrome (ARDS).
Köksel
Oğuz
O
Department of Thoracic Surgery, Medical Faculty Hospital, Mersin University 33179 Mersin, Turkey.
Yildirim
Cağlar
C
Tiftik
Rukiye Nalan
RN
Kubat
Havva
H
Tamer
Lülüfer
L
Cinel
Leyla
L
Kaplan
Murat Bayram
MB
Değirmenci
Ulaş
U
Ozdülger
Ali
A
Büyükafşar
Kansu
K
D000577:Amides / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D007275:Injections, Intravenous; D047908:Intracellular Signaling Peptides and Proteins; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000097:blood / Q000378:metabolism; D009566:Nitrates / Q000097:blood / Q000378:metabolism; D009573:Nitrites / Q000097:blood / Q000378:metabolism; D019301:Oleic Acid / Q000008:administration & dosage / Q000633:toxicity; D009195:Peroxidase / Q000097:blood / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D054460:rho-Associated Kinases
D000577:Amides; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D009566:Nitrates; D009573:Nitrites; D011725:Pyridines; C108830:Y 27632; D019301:Oleic Acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D008315:Malondialdehyde; D009195:Peroxidase; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases