title: Rho-kinase (ROCK-1 and ROCK-2) upregulation in oleic acid-induced lung injury and its restoration by Y-27632.
abstract: 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).
authors.affiliation: Department of Thoracic Surgery, Medical Faculty Hospital, Mersin University 33179 Mersin, Turkey.
authors.forename: Oğuz
authors.initials: O
authors.lastname: Köksel
authors.forename: Cağlar
authors.initials: C
authors.lastname: Yildirim
authors.forename: Rukiye Nalan
authors.initials: RN
authors.lastname: Tiftik
authors.forename: Havva
authors.initials: H
authors.lastname: Kubat
authors.forename: Lülüfer
authors.initials: L
authors.lastname: Tamer
authors.forename: Leyla
authors.initials: L
authors.lastname: Cinel
authors.forename: Murat Bayram
authors.initials: MB
authors.lastname: Kaplan
authors.forename: Ulaş
authors.initials: U
authors.lastname: Değirmenci
authors.forename: Ali
authors.initials: A
authors.lastname: Ozdülger
authors.forename: Kansu
authors.initials: K
authors.lastname: Büyükafşar
mesh_terms: 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
chemical_list: 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