Deferiprone, an Iron Chelator, is Preventive and Therapeutic in Experimental Crescentic Glomerulonephritis

Abstract

Crescentic glomerulonephritis represents the most severe form of antibody-mediated glomerulonephritis. It is an important cause of renal dysfunction worldwide and there is a need for more effective treatment. Deferiprone, an orally active iron chelator, is widely used in patients with thalassemia. Here we present the preventive and therapeutic effects of deferiprone in experimental crescentic glomerulonephritis. Nephrotoxic nephritis was induced in Wistar Kyoto rats, and preventive treatment with deferiprone substantially lowered glomerular crescent formation by 84%, with 70% reduction in proteinuria. In established glomerulonephritis, deferiprone treatment effectively halted glomerular inflammation, reversed progression of proteinuria, and prevented deterioration of renal function. Deferiprone reduced glomerular inflammatory cell proliferation in vivo. It was internalised by monocyte/macrophages and inhibited their proliferation in vitro, withoutshowing cellular toxicity. Interestingly, deferiprone showed a neutralizing effect on superoxide anions, and prevented the expression of monocyte chemoattractant protein-1 and matrix metalloproteinase 9, 12 and 14, by primary macrophages. These results suggest that deferiprone partly exerts its renal protective effect through inhibition of monocyte/macrophage proliferation and function by ironchelating and anti-oxidant properties, respectively. We conclude that deferiprone is an effective treatment in a severe and reproducible model of antibody-mediated glomerular inflammation that resembles human crescentic glomerulonephritis, indicating its therapeutic potential.

(5-Hydroxy-4-oxo-2-styryl-4H-pyridin-1-yl)-acetic Acid Derivatives as Multifunctional Aldose Reductase Inhibitors

“…Served as antivirus [24,25], anti-Alzheimer's disease [26] and even anti-diabetes [27][28][29][30] agents, synthetic 3-hydroxy-4(1H)-pyridinone derivatives may have potential for the development of ARI. Interestingly, a large amount of evidence has proven that synthetic 3-hydroxy-4(1H)-pyridinone derivatives exhibited remarkable activity of antioxidant, and they ameliorated oxidative stress by directly neutralizing superoxide anions [31][32][33]. Notably, novel 2-styryl-1H-pyridin-4-ones showed significant radical scavenging activity [34], illustrating that these compounds may be the desirable candidates with antioxidant capacity fighting against oxidative stress.…”