Melatonin ameliorates renal ischemia/reperfusion injury

• Published in: The Journal of surgical research 2004-02, Vol.116 (2), p.242-247
• Main Authors: Rodrı́guez-Reynoso, Sergio, Leal, Caridad, Portilla-de Buen, Eliseo, Castillo, Juan Carlos, Ramos-Solano, Francisco
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Creatinine - blood; General aspects; Glutathione - metabolism; inducible nitric oxide synthase; inflammatory response; Injuries of the urinary system. Foreign bodies. Diseases due to physical agents; ischemia/reperfusion; kidney; Kidney - metabolism; Kidney - pathology; lipid peroxidation; Lipid Peroxidation - drug effects; Male; Medical sciences; melatonin; Melatonin - pharmacology; Necrosis; neutrophil infiltration; nitric oxide; Nitric Oxide Synthase - metabolism; Nitric Oxide Synthase Type II; Peroxidase - metabolism; rat; Rats; Rats, Sprague-Dawley; Renal Circulation; Reperfusion Injury - metabolism; Reperfusion Injury - pathology; Traumas. Diseases due to physical agents
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2003.10.002

We studied whether melatonin is able to reduce organ damage during renal ischemia/reperfusion via its effects on the oxidative response in early and late reperfusion. Renal ischemia/reperfusion injury (I/R) was induced in two groups of rats by 75 min occlusion of the left renal artery and vein and right nephrectomy, followed by reperfusion. The formation of reactive oxygen species was evaluated in the early reperfusion phase (60 min) by lipid peroxidation products and glutathione assay. In the late reperfusion phase (24 h) tissue neutrophil infiltration, inducible nitric oxide synthase (iNOS) gene expression, and histopathology were evaluated. Groups received either systemic melatonin (MEL) or normal saline (NS). There were two nonischemic sham control groups, one with and another without melatonin (S+MEL and S). Creatinine was higher in the NS group at all times. A reduction in glutathione and increases in lipid peroxidation products and myeloperoxidase activity induced by I/R indicated renal injury involving reactive oxygen formation. Melatonin reversed this oxidant response and reduced the rise in creatinine and iNOS expression. Seven-day group survivals were 5/10 for NS, 8/10 for MEL, and 10/10 for both Sham groups. Exogenous melatonin is able to preserve renal functional status following I/R-induced injury by increasing glutathione and reducing lipid peroxidation in the early reperfusion phase, without any apparent effect on neutrophil infiltration in the late reperfusion phase.