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Lung Apoptotic Signalling and Oxidative Stress During Sub‐Chronic Administration of Doxorubicin to Wistar Rats
Author(s) -
Machado Nuno Gabriel,
Oliveira Paulo Jorge
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.970.4
Subject(s) - mitochondrial permeability transition pore , oxidative stress , apoptosis , pharmacology , doxorubicin , mitochondrion , caspase 3 , chemistry , mptp , cytochrome c , medicine , microbiology and biotechnology , biology , biochemistry , pathology , programmed cell death , chemotherapy , disease , parkinson's disease
Besides oxidative stress, mitochondrial dysfunction, including induction of the permeability transition pore (MPTP), inhibition of respiration and apoptosis has been implicated in Doxorubicin (DOX) cardiotoxicity. The aim of the present work was to determine if DOX causes an increase in selected apoptotic proteins and oxidative stress in the lung. Lungs from male Wistar rats subchronically treated with vehicle or DOX with seven weekly injections (2 mg/Kg) were collected and analyzed by Western Blotting for a) subunits of the mitochondrial respiratory chain b) selected proteins of the MPTP and c) selected pro and anti‐apoptotic proteins. Caspase 9‐ and 3‐like activities and protein carbonyls were also studied. After DOX treatment, no differences in protein carbonyls or caspase 9‐ and caspase 3‐like activities were observed. No alterations were also observed in proteins involved in the mitochondrial permeability transition pore, respiratory chain and in the apoptotic processes studied. The data demonstrate that sub‐chronic DOX treatment apparently does not trigger apoptosis or oxidative stress in the lungs. For this treatment schedule, we conclude that differences exist regarding the susceptibility of the heart and lung tissue for DOX treatment, although lung mitochondrial function must still be evaluated. Supported by research grant PTDC/SAU‐OSM/104731/2008 from the Portuguese FCT (to PO).