Sulforaphane Attenuates Gentamicin-Induced Nephrotoxicity: Role of Mitochondrial Protection
Open Access
- 1 January 2013
- journal article
- research article
- Published by Hindawi Limited in Evidence-Based Complementary and Alternative Medicine
- Vol. 2013, 1-17
- https://doi.org/10.1155/2013/135314
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.Keywords
Funding Information
- National Council of Science and Technology, Mexico (167949, 129838, IN210713, IN201910)
This publication has 81 references indexed in Scilit:
- General anesthesia as a possible GABAergic modulator affects visual processing in childrenFrontiers in Cellular Neuroscience, 2013
- Mitochondrial Regulation of Cell Cycle and ProliferationAntioxidants and Redox Signaling, 2012
- Apoptosis Induction in Primary Human Colorectal Cancer Cell Lines and Retarded Tumor Growth in SCID Mice by SulforaphaneEvidence-Based Complementary and Alternative Medicine, 2012
- Sulforaphane inhibits mitochondrial permeability transition and oxidative stressFree Radical Biology & Medicine, 2011
- Sulforaphane prevents microcystin-LR-induced oxidative damage and apoptosis in BALB/c miceToxicology and Applied Pharmacology, 2011
- Brain mitochondria from rats treated with sulforaphane are resistant to redox-regulated permeability transitionJournal of Bioenergetics and Biomembranes, 2010
- Direct quantitation of glucoraphanin in dog and rat plasma by LC–MS/MSJournal of Pharmaceutical and Biomedical Analysis, 2010
- Early Exposure to Anesthesia and Learning Disabilities in a Population-based Birth CohortAnesthesiology, 2009
- Molecular basis for chemoprevention by sulforaphane: a comprehensive reviewCellular and Molecular Life Sciences, 2007
- Gentamicin Causes Apoptosis at Low Concentrations in Renal LLC-PK 1 Cells Subjected to ElectroporationAntimicrobial Agents and Chemotherapy, 2006