stilbenes and Glomerulonephritis

Resveratrol, a natural polyphenolic phytoalexin, has been considered as a potential anti-inflammatory agent because of its suppressive effect on nuclear factor-kappaB (NF-kappaB). However, we recently found that treatment of glomerular mesangial cells with resveratrol significantly and dose-dependently enhanced NF-kappaB activation triggered by proinflammatory cytokines. This finding was evidenced by different reporter assays as well as by expression of an endogenous NF-kappaB-dependent gene, intercellular adhesion molecule-1. The NF-kappaB promoting effect of resveratrol was also observed in renal tubular LLCPK1 cells, but not in HepG2 hepatoma cells. In all cell types tested, treatment with resveratrol alone did not affect NF-kappaB activity. The enhanced activation of NF-kappaB by resveratrol progressed for at least 24 h and was accompanied by sustained down-regulation of an endogenous NF-kappaB inhibitor, IkappaBbeta, but not IkappaBalpha. Although expression of inducible nitric oxide synthase was suppressed by resveratrol, nitric oxide, a negative regulator of NF-kappaB, was not involved in the regulation of NF-kappaB by resveratrol. These data elucidated, for the first time, that resveratrol may enhance activation of NF-kappaB under certain circumstances.

Topics: Alkaline Phosphatase; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell Line; Cell Line, Tumor; Chemokine CCL2; Cytokines; Gene Expression Regulation; Glomerulonephritis; I-kappa B Proteins; Intercellular Adhesion Molecule-1; Kidney Glomerulus; Male; NF-kappa B; NF-KappaB Inhibitor alpha; Nitric Oxide; Rats; Rats, Sprague-Dawley; Resveratrol; Stilbenes; Tumor Necrosis Factor-alpha

The effect of resveratrol, a polyphenolic compound present in grapes and other plants, on proteinuria, hypoalbuminemia and hyperlipidemia was studied in rats with glomerulonephritis. The nephritis was induced by an intravenous injection of anti-rat kidney glomerular basement membrane rabbit antiserum. Nephritic rats were given oral intubation of resveratrol (5 mg/day/100 g body weight) for 14 days, while control nephritic rats as well as normal ones were similarly given vehicle alone. By resveratrol treatment, enlargement in liver and kidney due to nephritis induction was significantly reduced, together with partial restoration of nephritis-induced reduction in body weight gain. Both proteinuria and hypoalbuminemia, characteristic symptoms to nephrotic syndrome, were significantly remedied, that is, urinary protein excretion was suppressed and serum albumin concentration was increased by resveratrol treatment. Resveratrol also suppressed significantly hyperlipidemia incident to nephritis, the hypotriglyceridemic action being more prominent than the hypocholesterolemic one. From these results, resveratrol is suggested to be a potent anti-glomerulonephritic food factor capable of suppressing proteinuria, hypoalbuminemia and hyperlipidemia at the same time.

Topics: Administration, Oral; Albumins; Animals; Anti-Inflammatory Agents, Non-Steroidal; Basement Membrane; Blood Urea Nitrogen; Body Weight; Cholesterol; Disease Models, Animal; Eating; Glomerulonephritis; Hyperlipidemias; Hypoproteinemia; Kidney; Kidney Glomerulus; Liver; Male; Organ Size; Proteinuria; Rabbits; Rats; Rats, Wistar; Resveratrol; Stilbenes; Triglycerides