title: Pummelo protects Doxorubicin-induced cardiac cell death by reducing oxidative stress, modifying glutathione transferase expression, and preventing cellular senescence.
abstract: Citrus flavonoids have been shown to reduce cardiovascular disease (CVD) risks prominently due to their antioxidant effects. Here we investigated the protective effect of pummelo (Citrus maxima, CM) fruit juice in rat cardiac H9c2 cells against doxorubicin (DOX-) induced cytotoxicity. Four antioxidant compositions (ascorbic acid, hesperidin, naringin, and gallic acid) were determined by HPLC. CM significantly increased cardiac cell survival from DOX toxicity as evaluated by MTT assay. Reduction of cellular oxidative stress was monitored by the formation of DCF fluorescent product and total glutathione (GSH) levels. The changes in glutathione-S-transferase (GST) activity and expression were determined by enzyme activity assay and Western blot analysis, respectively. Influence of CM on senescence-associated β-galactosidase activity (SA-β-gal) was also determined. The mechanisms of cytoprotection involved reduction of intracellular oxidative stress, maintaining GSH availability, and enhanced GST enzyme activity and expression. DOX-induced cellular senescence was also attenuated by long-term CM treatment. Thus, CM fruit juice can be promoted as functional fruit to protect cells from oxidative cell death, enhance the phase II GSTP enzyme activity, and decrease senescence phenotype population induced by cardiotoxic agent such as DOX.
authors: Department of Preclinical Sciences, Faculty of Medicine, Thammasat University, Pathum Thani 12120, Thailand.
authors: L
authors: L
authors: Chularojmontri
authors: O
authors: O
authors: Gerdprasert
authors: S K
authors: SK
authors: Wattanapitayakul
references: Nutr Res. 2011 Jul;31(7):519-26
references: 21840468
references: Prog Cardiovasc Dis. 2007 Mar-Apr;49(5):330-52
references: 17329180
references: Anticancer Drugs. 2009 Jun;20(5):382-8
references: 19318911
references: J Biol Chem. 2001 Dec 14;276(50):47266-76
references: 11579094
references: Am J Clin Nutr. 2003 Jul;78(1):57-64
references: 12816771
references: Maturitas. 2010 Dec;67(4):343-7
references: 20729016
references: Toxicol Sci. 2007 Dec;100(2):513-24
references: 17890767
references: J Biol Chem. 2004 Jun 11;279(24):25535-43
references: 15054096
references: J Agric Food Chem. 2010 May 26;58(10):6069-74
references: 20420369
references: Basic Clin Pharmacol Toxicol. 2005 Jan;96(1):80-7
references: 15667600
references: BMC Pharmacol. 2009 Apr 15;9:7
references: 19368719
references: J Chromatogr B Analyt Technol Biomed Life Sci. 2007 Oct 1;857(2):202-9
references: 17689302
references: Am J Physiol Heart Circ Physiol. 2009 Dec;297(6):H2169-81
references: 19801496
references: Am J Physiol Heart Circ Physiol. 2004 Jun;286(6):H2057-64
references: 14726301
references: J Neurosci Res. 2007 Feb 15;85(3):497-503
references: 17171703
references: J Ethnopharmacol. 2006 Mar 8;104(1-2):113-8
references: 16226416
references: Mutat Res. 2001 Oct 1;482(1-2):21-6
references: 11535245
references: Gastric Cancer. 2008;11(1):23-32
references: 18373174
references: J Med Food. 2009 Apr;12(2):394-402
references: 19459743
references: Anticancer Res. 2010 Oct;30(10):3951-7
references: 21036708
references: J Agric Food Chem. 2008 Aug 13;56(15):6185-205
references: 18593176
references: Int J Oncol. 2010 Feb;36(2):491-500
references: 20043085
references: Anal Chem. 2010 Jun 15;82(12):5134-40
references: 20503971
references: Gerontology. 2008;54(1):24-31
references: 18196923
references: J Med Assoc Thai. 2009 Jun;92 Suppl 3:S43-51
references: 19705546
references: Am J Chin Med. 2010;38(3):569-84
references: 20503473
references: Cell Biol Toxicol. 2007 Jan;23(1):15-25
references: 17009097
references: Mutat Res. 2011 Sep 18;724(1-2):28-34
references: 21640195
references: Aging Cell. 2008 Mar;7(2):125-36
references: 18031568
references: Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9363-7
references: 7568133
references: Arch Immunol Ther Exp (Warsz). 2009 Nov-Dec;57(6):435-45
references: 19866340
references: Int J Food Sci Nutr. 2009;60 Suppl 6:107-15
references: 19381992
references: Anal Biochem. 1980 Jul 15;106(1):207-12
references: 7416462