title: Sulforaphane attenuates gentamicin-induced nephrotoxicity: role of mitochondrial protection.
abstract: Sulforaphane (SFN), an isothiocyanate naturally occurring in Cruciferae, induces cytoprotection in several tissues. Its protective effect has been associated with its ability to induce cytoprotective enzymes through an Nrf2-dependent pathway. Gentamicin (GM) is a widely used antibiotic; nephrotoxicity is the main side effect of this compound. In this study, it was investigated if SFN is able to induce protection against GM-induced nephropathy both in renal epithelial LLC-PK1 cells in culture and in rats. SFN prevented GM-induced death and loss of mitochondrial membrane potential in LLC-PK1 cells. In addition, it attenuated GM-induced renal injury (proteinuria, increases in serum creatinine, in blood urea nitrogen, and in urinary excretion on N-acetyl- β -D-glucosaminidase, and decrease in creatinine clearance and in plasma glutathione peroxidase activity) and necrosis and apoptosis in rats. The apoptotic death was associated with enhanced active caspase-9. Caspase-8 was unchanged in all the studied groups. In addition, SFN was able to prevent GM-induced protein nitration and decrease in the activity of antioxidant enzymes catalase and glutathione peroxidase in renal cortex. In conclusion, the protective effect of SFN against GM-induced acute kidney injury could be associated with the preservation in mitochondrial function that would prevent the intrinsic apoptosis and nitrosative stress.
authors: Departamento de Biología, Facultad de Química, UNAM, 04510 Mexico City, DF, Mexico.
authors: Mario
authors: M
authors: Negrette-Guzmán
authors: Sara
authors: S
authors: Huerta-Yepez
authors: Omar Noel
authors: ON
authors: Medina-Campos
authors: Zyanya Lucía
authors: ZL
authors: Zatarain-Barrón
authors: Rogelio
authors: R
authors: Hernández-Pando
authors: Ismael
authors: I
authors: Torres
authors: Edilia
authors: E
authors: Tapia
authors: José
authors: J
authors: Pedraza-Chaverri
references: Kidney Int. 2011 Jan;79(1):33-45
references: 20861826
references: Lung Cancer. 2011 Mar;71(3):298-305
references: 20638746
references: Evid Based Complement Alternat Med. 2012;2012:415231
references: 21804859
references: Mini Rev Med Chem. 2009 Jun;9(6):749-59
references: 19519500
references: Free Radic Biol Med. 2011 Dec 15;51(12):2164-71
references: 21986339
references: Kidney Int. 2010 May;77(10):861-9
references: 20164825
references: Biol Chem. 2003 Apr;384(4):567-74
references: 12751786
references: J Bioenerg Biomembr. 2010 Dec;42(6):491-7
references: 21061051
references: Eur J Pharmacol. 2011 Nov 30;670(2-3):578-85
references: 21925163
references: Phytother Res. 2006 Jan;20(1):76-8
references: 16397848
references: Proc Natl Acad Sci U S A. 1991 May 1;88(9):3671-5
references: 2023917
references: Pulm Pharmacol Ther. 2011 Feb;24(1):110-7
references: 20833254
references: Braz J Med Biol Res. 2009 Jul;42(7):614-20
references: 19466282
references: Free Radic Biol Med. 2000 Oct 1;29(7):602-11
references: 11033412
references: Exp Toxicol Pathol. 2012 Jul;64(5):503-8
references: 21129940
references: Toxicol Appl Pharmacol. 2011 Aug 15;255(1):9-17
references: 21684301
references: J Trace Elem Med Biol. 2011 Jul;25(3):125-9
references: 21696931
references: Cancer Epidemiol Biomarkers Prev. 1998 Dec;7(12):1091-100
references: 9865427
references: Free Radic Biol Med. 2003 Aug 1;35(3):317-24
references: 12885594
references: BMC Clin Pharmacol. 2004 Apr 30;4:5
references: 15119956
references: Toxicol Lett. 2010 Feb 15;192(3):278-85
references: 19913604
references: QJM. 2009 Dec;102(12):873-80
references: 19820138
references: Toxicology. 2011 Aug 15;286(1-3):20-7
references: 21575670
references: Fundam Clin Pharmacol. 2009 Aug;23(4):515-20
references: 19709328
references: Nephrol Dial Transplant. 2011 Jan;26(1):144-50
references: 20591815
references: Pharmacol Res. 2010 Apr;61(4):342-8
references: 19948220
references: Antimicrob Agents Chemother. 2006 Apr;50(4):1213-21
references: 16569831
references: Toxicol Lett. 2010 Nov 10;199(1):80-92
references: 20732396
references: J Exp Anim Sci. 1991;34(4):147-52
references: 1793742
references: Drug Chem Toxicol. 2012 Jul;35(3):258-63
references: 21939361
references: Kidney Int. 2010 May;77(10):841-3
references: 20431573
references: Antioxid Redox Signal. 2012 May 15;16(10):1150-80
references: 21967640
references: Life Sci. 2003 Oct 3;73(20):2543-56
references: 12967679
references: Trends Mol Med. 2012 Jun;18(6):337-47
references: 22578879
references: Free Radic Biol Med. 1996;21(4):457-62
references: 8886795
references: Nat Rev Mol Cell Biol. 2010 Dec;11(12):872-84
references: 21102612
references: Mol Nutr Food Res. 2008 Jun;52 Suppl 1:S128-38
references: 18327872
references: Methods Mol Biol. 2011;731:219-36
references: 21516411
references: Toxicol Lett. 2003 Apr 11;140-141:105-12
references: 12676456
references: Mol Cancer Ther. 2007 Mar;6(3):1013-21
references: 17339367
references: Pharmacol Res. 2010 Sep;62(3):179-86
references: 20434560
references: Cell Mol Life Sci. 2007 May;64(9):1105-27
references: 17396224
references: Toxicol Lett. 2000 Jul 27;116(1-2):45-9
references: 10906421
references: Cytotechnology. 2001 Mar;35(2):115-25
references: 19003288
references: Toxicol Appl Pharmacol. 2005 Aug 15;206(3):321-33
references: 16039943
references: J Pharm Biomed Anal. 2010 Aug 1;52(4):544-9
references: 20144518