Olfa Khazri1, Kamel Charradi2, Ferid Limam3, Michelle Veronique El May4, Ezzedine Aouani2. 1. 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. 2. 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. 3. Laboratoire des Substances Bio-Active (LSBA), Centre de Biotechnologie de Borj Cedria, BP-901, 2050 Hammam-Lif, Tunisia. 4. Unité de recherche no. 01/UR/07-08, Faculté de Medicine de Tunis, Tunisia.
Abstract
INTRODUCTION: 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. CONCLUSION: Data suggest that GSSE exerts potent antioxidant properties that could find potential application in the protection against bleomycin-induced lung fibrosis.
INTRODUCTION: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. CONCLUSION: Data suggest that GSSE exerts potent antioxidant properties that could find potential application in the protection against bleomycin-induced lung fibrosis.
Authors: Seok-Jo Kim; Paul Cheresh; Renea P Jablonski; Luisa Morales-Nebreda; Yuan Cheng; Erin Hogan; Anjana Yeldandi; Monica Chi; Raul Piseaux; Karen Ridge; C Michael Hart; Navdeep Chandel; G R Scott Budinger; David W Kamp Journal: Free Radic Biol Med Date: 2016-11-11 Impact factor: 7.376