Bioflavonoid quercetin inhibits mitosis and apoptosis of glomerular cells in vitro and in vivo.
Bioflavonoids have been regarded as therapeutic agents for a wide range of disease including inflammation. In this report, we investigated effects of bioflavonoid quercetin on mitosis and apoptosis of glomerular cells in vitro and in vivo. Serum-stimulated rat mesangial cells were treated with or without quercetin, and total cell number, percentages of mitotic cells, and incorporation of [(3)H]-thymidine were evaluated. All three assays showed that mitogenic activity of mesangial cells was markedly attenuated by quercetin. To examine the effect of quercetin on apoptosis, mesangial cells were pretreated with or without quercetin and stimulated by hydrogen peroxide or tumor necrosis factor-alpha. Hoechst staining and DNA ladder assay showed that both apoptotic responses were dramatically inhibited by quercetin. We further investigated effects of quercetin on in vivo mitosis and apoptosis of glomerular cells. Rats were administered with or without quercetin intraperitoneally, and nephrotoxic serum nephritis was induced. Immunohistochemical analyses showed that treatment with quercetin significantly reduced the number of proliferating cell nuclear antigen (+) cells and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (+) cells in the glomerulus. These data suggested that quercetin has the potential for inhibiting mitosis and apoptosis of glomerular cells both in vitro and in vivo.
Ishikawa
Y
Y
Renal Bioengineering Unit, Department of Medicine, University College Medical School, University College London, Mortimer Street, London, W1T 3AA, United Kingdom.
Kitamura
M
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D003470:Culture Media; D004247:DNA / Q000096:biosynthesis; D005920:Glomerular Mesangium / Q000166:cytology* / Q000187:drug effects; D020287:In Situ Nick-End Labeling; D007274:Injections, Intraperitoneal; D008297:Male; D008938:Mitosis / Q000187:drug effects*; D009393:Nephritis / Q000473:pathology; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011794:Quercetin / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors
D003470:Culture Media; D018809:Proliferating Cell Nuclear Antigen; D004247:DNA; D011794:Quercetin; D013936:Thymidine