Grape seed and skin extract protects against bleomycin-induced oxidative stress in rat lung.
BACKGROUND
Lung fibrosis is a common side effect of the chemotherapeutic agent bleomycin and current evidence suggests that reactive oxygen species play a key role in the development of lung injury. We examined whether grape seed and skin extract (GSSE), a polyphenolic mixture exhibiting antioxidant properties, is able to protect against bleomycin-induced lung oxidative stress and injury.


METHODS
Rats were pre-treated during three weeks either with vehicle (ethanol 10% control) or GSSE (4g/kg), then administered with a single high dose bleomycin (15mg/kg) at the 7th day.


RESULTS
Bleomycin increased lung lipoperoxidation, carbonylation and decreased antioxidant enzyme activities as catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx). Bleomycin also induced copper depletion from the lung and iron accumulation within the lung, but had no effect on either zinc nor manganese. Correlatively bleomycin decreased the copper associated enzyme tyrosinase, increased the zinc dependent lactate dehydrogenase (LDH) and did not affect the manganese dependent glutamine synthetase. GSSE efficiently counteracted almost all bleomycin-induced oxidative stress, biochemical and morphological changes of lung tissue.


CONCLUSIONS
Data suggest that GSSE exerts potent antioxidant properties that could find potential application in the protection against bleomycin-induced lung fibrosis.
Laboratoire des Substances Bio-Active (LSBA), Centre de Biotechnologie de Borj Cedria, BP-901, 2050 Hammam-Lif, Tunisia; Université de Carthage, Faculté des Sciences de Bizerte, 7021 Jarzouna, Tunisia. Electronic address: olfakhazribio@yahoo.com.
Olfa
O
Khazri
Laboratoire des Substances Bio-Active (LSBA), Centre de Biotechnologie de Borj Cedria, BP-901, 2050 Hammam-Lif, Tunisia; Université de Carthage, Faculté des Sciences de Bizerte, 7021 Jarzouna, Tunisia.
Kamel
K
Charradi
Laboratoire des Substances Bio-Active (LSBA), Centre de Biotechnologie de Borj Cedria, BP-901, 2050 Hammam-Lif, Tunisia.
Ferid
F
Limam
Unité de recherche no. 01/UR/07-08, Faculté de Medicine de Tunis, Tunisia.
Michelle Veronique
MV
El May
Laboratoire des Substances Bio-Active (LSBA), Centre de Biotechnologie de Borj Cedria, BP-901, 2050 Hammam-Lif, Tunisia; Université de Carthage, Faculté des Sciences de Bizerte, 7021 Jarzouna, Tunisia.
Ezzedine
E
Aouani
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001761:Bleomycin; D001835:Body Weight / Q000187:drug effects; D002154:Calpain / Q000378:metabolism; D002853:Chromatography, Liquid; D056604:Grape Seed Extract / Q000494:pharmacology*; D006949:Hyperlipidemias / Q000473:pathology; D042541:Intracellular Space / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000473:pathology*; D008297:Male; D008670:Metals / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D020011:Protective Agents / Q000494:pharmacology*; D050050:Protein Carbonylation / Q000187:drug effects; D017208:Rats, Wistar; D053719:Tandem Mass Spectrometry
D000975:Antioxidants; D056604:Grape Seed Extract; D008670:Metals; D020011:Protective Agents; D001761:Bleomycin; D002154:Calpain
Bleomycin; Grape seed and skin extract; Lung protection; Reactive oxygen species; Transition metals