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Pretreatment with melatonin protects against cyclophosphamide‐induced oxidative stress and renal damage in mice
Author(s) -
Goudarzi Mehdi,
Khodayar Mohammad Javad,
Hosseini Tabatabaei Seyed Mohammad Taghi,
Ghaznavi Habib,
Fatemi Iman,
Mehrzadi Saeed
Publication year - 2017
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/fcp.12303
Subject(s) - malondialdehyde , oxidative stress , nephrotoxicity , chemistry , glutathione peroxidase , blood urea nitrogen , superoxide dismutase , myeloperoxidase , kidney , glutathione , creatinine , nitric oxide , endocrinology , pharmacology , medicine , catalase , biochemistry , inflammation , enzyme
Cyclophosphamide ( CP ) is widely used in treatment of different cancers. Nephrotoxicity is one of the dose‐limiting side effects of CP . This study was carried out to investigate the effect of melatonin ( MEL ) on CP ‐induced nephrotoxicity in mice. In this study, 50 Swiss albino mice (20–25 g) were randomly divided into five groups. Mice were pretreated with MEL intraperitoneally (i.p) in doses of 5, 10 and 20 mg/kg for five consecutive days, and CP (200 mg/kg, i.p) was administrated on the 5th day 1 h after the last dose of MEL . Then on day 6, blood samples were collected to determine serum creatinine (Cr) and blood urea nitrogen ( BUN ) levels. The kidneys were used for histological examination, biochemical assays and real‐time PCR studies. Malondialdehyde ( MDA ), glutathione ( GSH ), protein carbonyl ( PC ), nitric oxide ( NO ) level, catalase ( CAT ), superoxide dismutase ( SOD ), glutathione peroxidase ( GP x) and myeloperoxidase ( MPO ) activity were assessed in renal tissue. In addition, the expression of SOD 2 and PG x1 was measured using real‐time PCR method in renal tissue. Results showed that CP administration significantly increases Cr, BUN , MDA , PC , NO level and MPO activity. It also decreases renal GSH level, SOD , GP x and CAT activity. Pretreatment with MEL (especially 20 mg/kg, i.p.) for 5 days prevented these changes; however, it did not affect the SOD activity. Our results revealed that MEL might be useful for prevention of the nephrotoxicity induced by CP through ameliorative effects on biochemical indices and oxidative stress parameters.