Korean J Nephrol.  2004 Mar;23(2):205-212.

Protective Effect of Melatonin on the Nephrotoxicity by Cisplatin

• Choi HJ
• Shin YH
• Mun KC
• Song DK
• Kim IC
• Seo SH
• Kwak CS
• Chang EJ
• Kim HC

Abstract

BACKGROUND
Cisplatin (CP), an antitumor agent widely used in the treatment of cancers, has nephrotoxicity. This side effect is closely related to oxidative stress. In the present study, we attempted to reduce CP-induced nephrotoxicity in rats by administering melatonin, an antioxidant. METHODS: Male Sprague-Dawley rats were divided into different groups and were treated as follows: (1) saline control; (2) CP (16 mg/kg, i.p.); (3) CP plus melatonin (10 mg/kg, i.p.). The rats were sacrificed at the 6th day after CP treatment. To evaluate renal damage, BUN, serum creatinine, creatinine clearance and microscopic examination were done. Hydrogen peroxide which is one of the oxygen free radicals, and malondialdehyde which is known as a marker of the oxygen free radical mediated injury, and the activities of the antioxidant enzymes such as superoxied dismutase, catalase, and glutathione peroxidase were also measured. RESULTS: CP-treated rats showed the increase of BUN, serum creatinine, malondialdehyde, hydrogen peroxide and superoxide dismutase (SOD) in kidney. And CP-treated rats also showed the decrease of creatinine clearance and catalase levels. CP-treated rats showed severe tubular necrosis in proximal convoluted tubules under the light microscopic examination. The light microscopic finding and all of the parameters except SOD were restored in the rats injected with CP plus melatonin than those with CP alone. SOD level was higher in the rats injected with CP plus melatonin than that with CP alone. CONCIUSION: These results suggest that melatonin suppresses CP-induced nephrotoxicity by suppressing the production of reactive oxygen species via the activation of SOD and catalase.

Keyword

Melatonin; Nephrotoxicity; Cisplatin; Oxidative stress

MeSH Terms

Animals
Catalase
Cisplatin*
Creatinine
Free Radicals
Glutathione Peroxidase
Humans
Hydrogen Peroxide
Kidney
Male
Malondialdehyde
Melatonin*
Necrosis
Oxidative Stress
Oxygen
Rats
Rats, Sprague-Dawley
Reactive Oxygen Species
Superoxide Dismutase
Catalase
Cisplatin
Creatinine
Free Radicals
Glutathione Peroxidase
Hydrogen Peroxide
Malondialdehyde
Melatonin
Oxygen
Reactive Oxygen Species
Superoxide Dismutase