Short- and long-term treatment with indometacin causes renal phospholipid alteration: a possible explanation for indomethacin nephrotoxicity.
Phospholipid content was studied in kidneys from rats treated with indometacin. Short-term treatment was performed by using low (1 and 5 mg/kg/day) and high (10 and 50 mg/kg/day) doses of indometacin. Long-term treatment was achieved by using only low doses of indometacin. Short-term treatment at low doses did not result in any change in the phospholipid content. In rats administered higher concentrations, indometacin caused a marked increase in all papillary phospholipid contents, but no effect was observed in the medulla, and an increase in sphingomyelin and phosphatidylethanolamine was observed in the cortex. Long-term treatment with administration of 1 mg/kg/day of indometacin led to an increase in all papillary phospholipids from the 2nd week of treatment. Medullary phospholipids also increased, but no changes were observed in cortical phospholipids. These results show that indometacin causes phospholipid accumulation in rat kidney and that the papilla is the most sensitive renal tissue.
Fernández-Tomé
M C
MC
Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
Sterin-Speziale
N B
NB
D000818:Animals; D007213:Indomethacin / Q000009:adverse effects* / Q000494:pharmacology; D007668:Kidney / Q000737:chemistry / Q000187:drug effects*; D007679:Kidney Medulla / Q000737:chemistry / Q000187:drug effects; D008297:Male; D010713:Phosphatidylcholines / Q000032:analysis; D010714:Phosphatidylethanolamines / Q000032:analysis; D010716:Phosphatidylinositols / Q000032:analysis; D010718:Phosphatidylserines / Q000032:analysis; D010743:Phospholipids / Q000032:analysis*; D051381:Rats; D017208:Rats, Wistar; D013109:Sphingomyelins / Q000032:analysis
D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010716:Phosphatidylinositols; D010718:Phosphatidylserines; D010743:Phospholipids; D013109:Sphingomyelins; D007213:Indomethacin