Reduction of cisplatin toxicity in cultured renal tubular cells by the bioflavonoid quercetin.
Quercetin (QC), a polyphenolic compound widely distributed in fruits and vegetables has recently gained interest due to its cisplatin (CP) sensitizing properties in cancer cells. It is currently unknown, whether quercetin also increases the susceptibility of the kidneys to cisplatin toxicity. We studied the effects of various bioflavonoids on CP toxicity in an in vitro model of cultured tubular epithelial cells (LLC-PK1). Viability of LLC-PK1 cells, as assessed by lactate dehydrogenase (LDH) release and MTT-test, was affected by CP (100-400 microM) in a time and dose dependent fashion. Pretreatment of cells with QC for 3 h significantly reduced the extent of cell damage. The protective activity of QC was concentration dependent, starting at 10-25 microM and reaching a plateau between 50 and 100 microM. Other bioflavonoids (catechin, silibinin, rutin) did not diminish cellular injury, even at higher concentrations (100-500 microM). Quercetin itself showed some intrinsic cytotoxicity at concentrations exceeding 75 microM. Our data indicate that quercetin reduces cisplatin toxicity in cultured tubular epithelial cells. The exact mechanism of protection is unclear, though scavenging of free oxygen radicals may play an important role.
Department of Medicine, University of Saarland, Homburg/Saar, Germany.
M K
MK
Kuhlmann
E
E
Horsch
G
G
Burkhardt
M
M
Wagner
H
H
Köhler
D000818:Animals; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D002945:Cisplatin / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D005419:Flavonoids / Q000494:pharmacology; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D018374:LLC-PK1 Cells; D011794:Quercetin / Q000494:pharmacology*; D013552:Swine; D013778:Tetrazolium Salts; D013844:Thiazoles
D000970:Antineoplastic Agents; D005419:Flavonoids; D013778:Tetrazolium Salts; D013844:Thiazoles; D011794:Quercetin; D007770:L-Lactate Dehydrogenase; C022616:thiazolyl blue; D002945:Cisplatin