Melatonin attenuates acute renal failure and oxidative stress induced by mercuric chloride in rats.
We evaluated the effect of melatonin (Mel), a potent scavenger of reactive oxygen species, in the course of HgCl(2)-induced acute renal failure. Rats received by gastric gavage 1 mg/kg of Mel (n = 21) or vehicle (n = 21), 30 min before the subcutaneous injection of HgCl(2) (2.5 mg/kg). Rats were killed at 24, 48, and 72 h, and plasma creatinine (S(cr)), renal histology, proliferative activity, apoptosis, and superoxide-producing cells were studied. We also determined the renal content of malondialdehyde (MDA) and glutathione (GSH) and the activities of glutathione peroxidase and catalase. Mel pretreatment (Mel plasma levels of 3.40 +/- 3.15 microgram/ml at the time of HgCl(2) injection) prevented the increment in S(cr) and reduced tubular necrosis from 41.0 +/- 10.5 to 4.2 +/- 5.1% of proximal tubules (P < 0.01). Apoptosis and postnecrotic proliferative activity were twice more intense in the group untreated with Mel. Increment in renal content of MDA and decrease in GSH resulting from HgCl(2) toxicity were prevented by Mel. Mel also induced an important reduction in superoxide-positive cells. In contrast to the beneficial effects of pretreatment with Mel, the administration of Mel in conjunction with HgCl(2) had no effect on the oxidative damage and did not prevent nephrotoxicity. We conclude that the beneficial effects of pharmacological doses of Mel are due to its antioxidant properties.
Nava
M
M
Renal Service and Laboratory, Hospital Universitario, Maracaibo 4001-a, Venezuela.
Romero
F
F
Quiroz
Y
Y
Parra
G
G
Bonet
L
L
Rodríguez-Iturbe
B
B
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008550:Melatonin / Q000378:metabolism / Q000494:pharmacology*; D008627:Mercuric Chloride; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism
D013481:Superoxides; D008315:Malondialdehyde; D008627:Mercuric Chloride; D003404:Creatinine; D005978:Glutathione; D008550:Melatonin