Lipoxin A4 and benzo‐lipoxin A4 attenuate experimental renal fibrosis

• Published in: The FASEB journal 2011-09, Vol.25 (9), p.2967-2979
• Main Authors: Börgeson, Emma, Docherty, Neil G., Murphy, Madeline, Rodgers, Karen, Ryan, Aidan, O'Sullivan, Tim P., Guiry, Patrick J., Goldschmeding, Roel, Higgins, Debra F., Godson, Catherine
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Apoptosis - drug effects; Collagen - genetics; Collagen - metabolism; Disease Models, Animal; eicosanoids; Fibrosis - drug therapy; Fibrosis - prevention & control; Gene Expression Regulation; Kidney - drug effects; Kidney - pathology; Kidney Diseases - drug therapy; Kidney Diseases - pathology; Kidney Diseases - prevention & control; Ligation; Lipoxins - chemistry; Lipoxins - therapeutic use; Male; Rats; Rats, Wistar; TGF‐β; Transforming Growth Factor beta1 - genetics; Transforming Growth Factor beta1 - metabolism; tubulointerstial fibrosis; unilateral ureteric obstruction
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.11-185017

ABSTRACT Unresolved inflammation underlies the development of fibrosis and organ failure. Here, we investigate the potential of the proresolving eicosanoid lipoxinA4 (LXA4) and its synthetic analog benzo‐LXA4 to prophylactically modulate fibrotic and inflammatory responses in a model of early renal fibrosis, unilateral ureteric obstruction (UUO). Male Wistar rats (Animalia, Chordata, Rattus norvegicus) were injected intravenously with vehicle (0.1% ethanol), LXA4 (45 μg/250‐g rat), or benzo‐LXA4 (15 μg/250‐g rat) 15 min prior to surgery and sacrificed 3 d postligation. Renal gene and protein expression, collagen deposition, macrophage infiltration, and apoptosis were analyzed using manipulated kidneys from sham operations as control. Lipoxins (LXs) attenuated collagen deposition and renal apoptosis (P