title: Expression of metallothioneins I and II in kidney of doxorubicin-treated rats.
abstract: Metallothioneins I/II (MT) are commonly expressed in mammalian tissues and are highly inducible in the response to stress conditions. Doxorubicin (DOX) intoxication promotes oxidative stress and subsequent apoptosis leading to kidney damage. The present study investigates a correlation between endogenous MT expression and DOX-induced apoptosis in renal tubular cells. Experiments were conducted on Buffalo rats receiving DOX (8 mg/kg b.w. for 3 weeks) versus control rats injected with saline. The histopathological alterations and apoptosis (TUNEL) were evaluated in tissue sections. MT expression and tissue localization was examined using immunohistochemical method (IHC). Western blot (WB) was used to evaluate pro-caspase-3, active caspase-3 and MT expression level in tissue homogenates. Examination of renal tissue revealed severe nephrotoxicity in DOX-treated animals. Apoptosis was observed in distal convoluted tubular cells, whereas MT was detected in proximal tubular cells. A significant increase in pro-caspase-3, active caspase-3 and MT expression levels (WB) were seen in DOX group. Positive correlations between histopathological lesions, apoptosis and MT expression were observed. The results obtained in this study could suggest the protective and antiapoptotic effect of MT expression in renal proximal tubular cells under DOX intoxication.
authors.affiliation: Department of Evolutionary Biology and Conservation of Vertebrates, University of Wroclaw, Sienkiewicza 21, 50-335 Wroclaw, Poland; Department of Histology and Embryology, Wroclaw Medical University, Chalubinskiego 6a, 50-368 Wroclaw, Poland. Electronic address: magdalena.chmielewska@uni.wroc.pl.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Chmielewska
authors.affiliation: Department of Pathomorphology, Wroclaw Medical University, Marcinkowskiego 1, 50-368 Wroclaw, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Symonowicz
authors.affiliation: Department of Histology and Embryology, Wroclaw Medical University, Chalubinskiego 6a, 50-368 Wroclaw, Poland.
authors.forename: Bartosz
authors.initials: B
authors.lastname: Pula
authors.affiliation: Department of Biochemistry, Pharmacology and Toxicology, Wroclaw University of Environmental and Life Sciences, Norwida 31, 50-375 Wroclaw, Poland; Laboratory of Glycobiology and Cell Interactions, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wroclaw, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Owczarek
authors.affiliation: Department of Histology and Embryology, Wroclaw Medical University, Chalubinskiego 6a, 50-368 Wroclaw, Poland.
authors.forename: Marzenna
authors.initials: M
authors.lastname: Podhorska-Okolow
authors.affiliation: Department of Biochemistry, Pharmacology and Toxicology, Wroclaw University of Environmental and Life Sciences, Norwida 31, 50-375 Wroclaw, Poland; Laboratory of Glycobiology and Cell Interactions, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wroclaw, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Ugorski
authors.affiliation: Department of Histology and Embryology, Wroclaw Medical University, Chalubinskiego 6a, 50-368 Wroclaw, Poland; Department of Physiotherapy, University School of Physical Education, Paderewskiego 35, 51-612, Wroclaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Dziegiel
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D004317:Doxorubicin / Q000633:toxicity*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007668:Kidney / Q000187:drug effects*; D008297:Male; D008668:Metallothionein / Q000096:biosynthesis*; D051381:Rats
chemical_list: D000903:Antibiotics, Antineoplastic; C491055:Mt2A protein, rat; D004317:Doxorubicin; D008668:Metallothionein
keywords: Apoptosis; Doxorubicin; Metallothionein; Nephrotoxicity