Resveratrol attenuates doxorubicin-induced cellular damage by modulating nitric oxide and apoptosis

被引:63
作者
Oktem, Gulperi [1 ]
Uysal, Aysegul [1 ]
Oral, Onur [2 ]
Sezer, Ebru Demirel [3 ]
Olukman, Murat [4 ]
Erol, Ayse [5 ]
Akgur, Serap A. [5 ]
Bilir, Ayhan [6 ]
机构
[1] Ege Univ, Fac Med, Dept Histol & Embryol, TR-35100 Izmir, Turkey
[2] Prov Hlth Directorate, Konak ACSAP Ctr 12, Izmir, Turkey
[3] Ege Univ, Fac Med, Dept Med Biochem, TR-35100 Izmir, Turkey
[4] Ege Univ, Fac Med, Dept Pharmacol, TR-35100 Izmir, Turkey
[5] Ege Univ, Drug Addict Toxicol & Drug Sci Inst, TR-35100 Izmir, Turkey
[6] Istanbul Univ, Fac Med, Dept Histol & Embryol, Istanbul, Turkey
关键词
Apoptosis; Doxorubicin; Nitric oxide; Resveratrol; Ultrastructure; ADRIAMYCIN TOXICITY; NATURAL-PRODUCT; CELLS; P53; CARDIOTOXICITY; SUPEROXIDE; ISCHEMIA; PROTECTS; PATHWAY; ARREST;
D O I
10.1016/j.etp.2010.11.001
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Although doxorubicin (DOX) is a commonly used chemotherapeutic agent its clinical use is restricted due to its organ toxicities. The present investigation relates to reducing DOX induced side effects to the liver, kidney and ileum by usage of the antioxidant, anti-inflammatory agent, resveratrol (RES) and to investigate the role of nitric oxide synthase (NOS) in the process. Wistar rats were divided into four groups: control (saline i.p); DOX (20 mg/kg i.p), RES (20 mg/kg i.p) and DOX (20 mg/kg i.p) + RES (20 mg/kg i.p). Immunohistochemical activity of both iNOS and eNOS were evaluated after DOX treatment and ultrastructural changes such as cellular damage and mitochondrial degeneration were evaluated. Degenerative ultrastructural changes were demonstrated especially in the DOX treated group. Variations in biochemical marker levels of oxidative stress on ischemia in tissues were not observed. Our data indicate that RES may prevent cellular damage in the early phase of DOX induced toxicity. RES could be used with its beneficial effects during early cellular damage in organ toxicity after DOX treatment in cancer patients. (C) 2010 Published by Elsevier GmbH.
引用
收藏
页码:471 / 479
页数:9
相关论文
共 42 条
[1]   Protective effect of melatonin against adriamycin toxicity in the rat [J].
Agapito, MT ;
Antolín, Y ;
del Brio, MT ;
López-Burillo, S ;
Pablos, MI ;
Recio, JM .
JOURNAL OF PINEAL RESEARCH, 2001, 31 (01) :23-30
[2]  
Anandakumar PP, 2007, INDIAN J EXP BIOL, V45, P1045
[3]   Nitric oxide protects the ultrastructure of pancreatic acinar cells in the course of caerulein-induced acute pancreatitis [J].
Andrzejewska, A ;
Jurkowska, G .
INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, 1999, 80 (06) :317-324
[4]   Resveratrol causes arrest in the S-phase prior to Fas-independent apoptosis in CEM-C7H2 acute leukemia cells [J].
Bernhard, D ;
Tinhofer, I ;
Tonko, M ;
Hübl, H ;
Ausserlechner, MJ ;
Greil, R ;
Kofler, R ;
Csordas, A .
CELL DEATH AND DIFFERENTIATION, 2000, 7 (09) :834-842
[5]   Biological effects of resveratrol [J].
Bhat, KPL ;
Kosmeder, JW ;
Pezzuto, JM .
ANTIOXIDANTS & REDOX SIGNALING, 2001, 3 (06) :1041-1064
[6]  
BILLINGHAM ME, 1978, CANCER TREAT REP, V62, P865
[7]  
BORIES PN, 1995, CLIN CHEM, V41, P904
[8]  
Bulucu F, 2008, J NEPHROL, V21, P576
[9]   CYTOKINES REGULATE ENDOTOXIN STIMULATION OF ENDOTHELIAL-CELL ARGININE TRANSPORT [J].
CENDAN, JC ;
SOUBA, WW ;
COPELAND, EM ;
LIND, DS .
SURGERY, 1995, 117 (02) :213-219
[10]   Oxidative damage precedes nitrative damage in adriamycin-induced cardiac mitochondrial injury [J].
Chaiswing, L ;
Cole, MP ;
St Clair, DK ;
Ittarat, W ;
Szweda, LI ;
Oberley, TD .
TOXICOLOGIC PATHOLOGY, 2004, 32 (05) :536-547