title: D(+) galactosamine induced oxidative and nitrosative stress-mediated renal damage in rats via NF-κB and inducible nitric oxide synthase (iNOS) pathways is ameliorated by a polyphenol xanthone, mangiferin.
abstract: The present study investigated the possible protective effect of mangiferin against D(+) galactosamine (DGal)-induced nephrotoxicity. DGal intoxication increased reactive oxygen species (ROS), reactive nitrogen species and tumor necrosis factor-α (TNF-α) production and disturbed the antioxidant machineries in the kidney tissue. Mangiferin treatment post to DGal exposure reduced all these DGal-induced adverse effects. Signal transduction studies showed that DGal significantly increased the protein expression of Bax, cytochrome c, caspase 3/9 and inducible nitric oxide synthase (iNOS) in the cytosol and NF-κB in nuclear fraction. The same exposure, on the other hand, reduced the protein expression of Bcl-2 in the cytosol. Mangiferin treatment could, however, reduce the DGal-induced up-regulation of cytochrome c, NF-κB, iNOS, caspase 3/9 and alter the reciprocal regulation of Bcl-2 family proteins. Histological studies also revealed the nephroprotective effect of mangiferin against DGal induced nephrotoxicity. Combining, results suggest that mangiferin protects rat's kidney in DGal-induced oxidative/nitrosative stress and acute nephrotoxicity via its antioxidant activities.
authors: Division of Molecular Medicine, Bose Institute, CIT Scheme VII M, West Bengal, Kolkata, India.
authors: Manoranjan
authors: M
authors: Ghosh
authors: Joydeep
authors: J
authors: Das
authors: Parames C
authors: PC
authors: Sil
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001806:Blood Urea Nitrogen; D002474:Cell-Free System; D002851:Chromatography, High Pressure Liquid; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D005688:Galactosamine; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D018384:Oxidative Stress; D050050:Protein Carbonylation; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D051437:Renal Insufficiency / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D044004:Xanthones / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D051017:Apoptosis Regulatory Proteins; D016166:Free Radical Scavengers; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D044004:Xanthones; C013592:mangiferin; D009569:Nitric Oxide; D008315:Malondialdehyde; D005688:Galactosamine; D003404:Creatinine; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat