Direct toxicity of nonsteroidal antiinflammatory drugs for renal medullary cells

Proceedings of the National Academy of Sciences of the United States of America
G M RochaM B Burg

Abstract

Antipyretic analgesics, taken in large doses over a prolonged period, cause a specific form of kidney disease, characterized by papillary necrosis and interstitial scarring. Epidemiological evidence incriminated mixtures of drugs including aspirin (ASA), phenacetin, and caffeine. The mechanism of toxicity is unclear. We tested the effects of ASA, acetaminophen (APAF, the active metabolite of phenacetin), caffeine, and other related drugs individually and in combination on mouse inner medullary collecting duct cells (mIMCD3). The number of rapidly proliferating cells was reduced by approximately 50% by 0.5 mM ASA, salicylic acid, or APAF. The drugs had less effect on confluent cells, which proliferate slowly. Thus, the slow in vivo turnover of IMCD cells could explain why clinical toxicity requires very high doses of these drugs over a very long period. Caffeine greatly potentiated the effect of acetaminophen, pointing to a potential danger of the mixture. Cyclooxygenase (COX) inhibitors, indomethacin and NS-398, did not reduce cell number except at concentrations greatly in excess of those that inhibit COX. Therefore, COX inhibition alone is not toxic. APAF arrests most cells in late G(1) and S and produces a mixed form of cell...Continue Reading

References

Jan 1, 1978·Kidney International·J H Shelley
Oct 1, 1976·CRC Critical Reviews in Toxicology·I Rosner
Aug 1, 1991·Annals of Internal Medicine·D P SandlerC R Weinberg
Jan 1, 1989·American Journal of Nephrology·W PommerM Molzahn
Jul 26, 1972·Nature: New Biology·R FlowerJ R Vane
Jan 1, 1973·Acta Pharmacologica Et Toxicologica·F Andreasen
Jun 15, 1984·JAMA : the Journal of the American Medical Association
Nov 1, 1980·Kidney International·G G Duggin
Apr 1, 1995·Mutation Research·G BrunborgJ K Hongslo
May 1, 1996·Current Opinion in Nephrology and Hypertension·M J KlagT V Perneger
Jan 22, 1998·Proceedings of the National Academy of Sciences of the United States of America·T A ChanK W Kinzler
Apr 3, 1999·The Journal of Biological Chemistry·O MirochnitchenkoM Inouye
Feb 9, 2000·American Journal of Physiology. Renal Physiology·L MicheaM B Burg
Apr 25, 2000·Annual Review of Medicine·J A Baron, R S Sandler

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Citations

Dec 29, 2007·Journal of Environmental Science and Health. Part. B, Pesticides, Food Contaminants, and Agricultural Wastes·Eun-Kee ParkBruce D Hammock
Feb 8, 2003·Current Atherosclerosis Reports·Richard J Bing
Sep 5, 2003·European Journal of Pharmacology·Yoshimi TsuchiyaKazuo T Suzuki
Aug 18, 2005·Toxicologic Pathology·Yoshimi TsuchiyaKazuo T Suzuki
Dec 1, 2007·Journal of Toxicology and Environmental Health. Part a·Eun-Kee ParkBruce D Hammock
Oct 21, 2015·Journal of Fluorescence·Elmas GökoğluAyşe Uzgören Baran
May 30, 2015·The Veterinary Clinics of North America. Equine Practice·Shannon McLeland
Jan 5, 2002·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Pascal MeierJérôme Rossert
Jun 5, 2002·Home Healthcare Nurse·Patricia J Neafsey, Juliette Shellman
Jul 12, 2005·American Journal of Physiology. Renal Physiology·Rania Nasrallah, Richard L Hébert
Nov 5, 2013·The Journal of Biological Chemistry·Leeann J BoermaMatthew B Renfrow
Mar 29, 2003·The Journal of Pharmacology and Experimental Therapeutics·Qi CaiMaurice B Burg
May 15, 2004·The Journal of Pharmacy and Pharmacology·Almira RamanavicieneArunas Ramanavicius

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