title: Genistein modulates NF-κB-associated renal inflammation, fibrosis and podocyte abnormalities in fructose-fed rats.
abstract: The study determines the effect of genistein on inflammatory status and expression of nuclear factor-kappa B (NF-κB p65), transforming growth factor-β1 (TGF-β1) and receptor for advanced glycation end products (RAGE) in kidney of fructose-fed rats. Adult male Wistar rats were fed a diet containing either starch or fructose as the source of carbohydrate. Fifteen days later, after confirming the development of insulin resistance in fructose-fed rats, the rats in each dietary group were divided into two and treated with either genistein (1 mg/kg/day) in 30% dimethylsulfoxide (DMSO) or 30% DMSO alone for the next 45 days. The expression of NF-κB P(65), TGF-β1 and RAGE, histochemical localization of α-smooth muscle actin (α-SMA), levels of tumour necrosis factor-α (TNF-α) and interleukin-6(IL-6) and ultrastructural analysis were performed at the end of the experimental period. Fructose-fed rats displayed inflammatory changes in kidney. Increased expression of TGF-β1 and RAGE in cytosol and NF-κB p65 in nuclear fraction were observed. α-SMA expression was higher in fructose-fed rat kidney. Proliferation of connective tissue was evident from increased collagen deposition in perivascular and intraglomerular regions. Administration of genistein to fructose-fed rats reduced inflammation, fibrogenesis and NF-κB activation. Genistein also mitigated the structural changes such as basement membrane thickening, reduction in podocyte number and loss of glomerular filtration barrier integrity. These findings suggest that genistein prevents inflammation, fibrosis and early nephropathic changes in fructose-fed insulin resistant rats secondary to the attenuation of NF-κB activation.
authors.affiliation: Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalai Nagar-608 002, Tamil Nadu, India.
authors.forename: Nallasamy
authors.initials: N
authors.lastname: Palanisamy
authors.forename: Sriramajayam
authors.initials: S
authors.lastname: Kannappan
authors.forename: Carani Venkataraman
authors.initials: CV
authors.lastname: Anuradha
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000097:blood; D003094:Collagen / Q000378:metabolism; D004040:Dietary Carbohydrates / Q000009:adverse effects*; D005355:Fibrosis; D005632:Fructose / Q000009:adverse effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D019833:Genistein / Q000494:pharmacology* / Q000627:therapeutic use; D007249:Inflammation / Q000097:blood / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015850:Interleukin-6 / Q000097:blood; D007674:Kidney Diseases / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D050199:Podocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000199:Actins; D015415:Biomarkers; D004040:Dietary Carbohydrates; D015850:Interleukin-6; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D051996:Transcription Factor RelA; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D005632:Fructose; D003094:Collagen; D019833:Genistein