title: 21-Aminosteroids block neutrophil infiltration and provide liver protection independent of NO2-/NO3- levels.
abstract: 21-Aminosteroids are antioxidant compounds that prevent iron-dependent lipid peroxidation and improve cell viability. In this work we attempt to define the role of 21-aminosteroids in liver ischemia and reperfusion and assess their possible mode of action, specifically their effect on neutrophil infiltration and nitrite/nitrate levels. Total liver ischemia for 90 min was produced in the rat with the use of a portosystemic shunt. Three groups of animals were studied. One group received the 21-aminosteroid U-74389G (10 mg/ kg) divided into two equal doses 10 min prior to ischemia (7 mg/kg) and 10 min before reperfusion (3 mg/ kg). The two other groups included the sham and the control animals. We studied survival at 7 days and serum liver enzymes, liver myeloperoxidase, plasma nitrites, nitrates, and liver histology at 6 hr postreperfusion. Animal survival improved from 13% in the ischemic control to 52% in the lazaroid treated group (P < 0.05). We observed significant improvements in liver function tests, liver myeloperoxidase levels, as well as in the liver histology (P < 0.05). We could not find statistical difference in plasma nitrite/nitrate (P > 0.1). The 21-aminosteroids significantly improved animal survival after total liver ischemia, through a mechanism that includes blocking neutrophil infiltration which is independent from nitrite/nitrate levels.
authors.affiliation: Surgical Research Institute at Borgess Medical Center, Kalamazoo, Michigan 49001, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Palma-Vargas
authors.forename: A H
authors.initials: AH
authors.lastname: Toledo
authors.forename: F J
authors.initials: FJ
authors.lastname: García-Criado
authors.forename: K
authors.initials: K
authors.lastname: Misawa
authors.forename: F
authors.initials: F
authors.lastname: López-Neblina
authors.forename: L H
authors.initials: LH
authors.lastname: Toledo-Pereyra
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D008099:Liver / Q000098:blood supply* / Q000187:drug effects; D008297:Male; D009504:Neutrophils / Q000187:drug effects*; D009566:Nitrates / Q000097:blood*; D009573:Nitrites / Q000097:blood*; D009195:Peroxidase / Q000378:metabolism; D011281:Pregnatrienes / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*
chemical_list: D000975:Antioxidants; D009566:Nitrates; D009573:Nitrites; D011281:Pregnatrienes; C074965:U 74389F; D009195:Peroxidase