title: Role of exogenous melatonin in reducing the nephrotoxic effect of daunorubicin and doxorubicin in the rat.
abstract: The aim of these studies was to examine the nephroprotective effect of melatonin following the anthracycline administration [daunorubicin (DNR); doxorubicin (DOX)] in rats. Application of these drugs in chemotherapy is limited because of their cardiotoxicity and nephrotoxicity. Rats of the Buffalo strain were divided into groups according to the cytostatic drug used, its dose and sequence of administration [DNR or DOX single (i.v.) dose of 10 mg/kg b.w., i.e. acute intoxication and 3 mg/kg b.w. (i.v.) weekly for 3 wk, subchronic intoxication]. Melatonin was administered subcutaneously before and after every injection of a cytostatic drug at a dose of 10 mg/kg b.w. The severity of renal alterations was examined both biochemically [levels of lipid peroxidation markers, malonyldialdehyde (MDA) and 4-hydroxyalkenals (4-HDA)], or histologically. A statistically significant decrease in renal damage was noted after melatonin administration to acutely or subchronically intoxicated DNR-treated and DOX-treated rats. Biochemical assays revealed significant decreases in MDA and 4-HDA levels following application of melatonin during subchronic DNR or DOX intoxication. In summary, melatonin was found to exert a protective effect on the kidney, which was particularly evident after subchronic DOX and DNR intoxication, using both histological or biochemical methods.
authors.affiliation: Department of Histology and Embryology, Wrocław Medical University, Chałubińskiego 6a, Wrocław, Poland. piotr@hist.am.wroc.pl
authors.forename: Piotr
authors.initials: P
authors.lastname: Dziegiel
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Suder
authors.forename: Paweł
authors.initials: P
authors.lastname: Surowiak
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Jethon
authors.forename: Jerzy
authors.initials: J
authors.lastname: Rabczyński
authors.forename: Lidia
authors.initials: L
authors.lastname: Januszewska
authors.forename: Mirosław
authors.initials: M
authors.lastname: Sopel
authors.forename: Maciej
authors.initials: M
authors.lastname: Zabel
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D003630:Daunorubicin / Q000633:toxicity*; D004317:Doxorubicin / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation; D008315:Malondialdehyde / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D011915:Rats, Inbred BUF
chemical_list: D000903:Antibiotics, Antineoplastic; D020011:Protective Agents; D008315:Malondialdehyde; D004317:Doxorubicin; D008550:Melatonin; D003630:Daunorubicin