Melatonin ameliorates renal ischemia/reperfusion injury.
BACKGROUND
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.


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
Rodríguez-Reynoso
Sergio
S
Surgical Research Division, Centro de Investigación Biomédica de Occidente, IMSS, Guadalajara, Jal. México Mexico.
Leal
Caridad
C
Portilla-de Buen
Eliseo
E
Castillo
Juan Carlos
JC
Ramos-Solano
Francisco
F
D000818:Animals; D003404:Creatinine / Q000097:blood; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D009336:Necrosis; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology*
D003404:Creatinine; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D005978:Glutathione; D008550:Melatonin