Clofibric and ethacrynic acids prevent experimental pyelonephritis by Escherichia coli in mice.
Interfering Escherichia coli attachment to the urinary tract, using P-fimbriation inhibitors, can prevent pyelonephritis. Clofibric and ethacrynic acids are organic compounds structurally related, but with different pharmacological uses. These agents are potentially active in the urinary tract due to its elimination in an unaltered form by the renal route. This study described a pyelonephritogenic E. coli strain, grown in the presence of sub-inhibitory concentrations of clofibric or ethacrynic acids (0.1 and 1 mM, respectively), which exhibits inhibition of P1 erythrocytes agglutination and a drastic decrease in fimbriation, using electron microscopy and quantitative analyses of superficial proteins (decrease to a 17-25% in comparison with the control). In vivo assays were performed using ascending urinary tract infection in mice. The treatment with therapeutic doses of the drugs, administered 2 days before the bacterial challenge and daily until the end of the experiment (22 days), abolished renal infection after 7-10 days of drug exposure. Within this period clofibric acid did not produce adverse effects on the renal parenchyma. However, ethacrynic acid caused pyelitis and tubular cellular desquamation. These results suggested that clofibric acid might be useful in the short-term prophylaxis of urinary tract infection.
Balagué
Claudia E
CE
Laboratorio de Toxicología Experimental, Universidad Nacional de Rosario, Suipacha 531, 2000 Rosario, Argentina. tonu14@aol.com
de Ruiz
Clara Silva
CS
Rey
Rosario
R
de Duffard
Ana María Evangelista
AM
Nader-Macías
María Elena
ME
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D000907:Antibodies, Bacterial / Q000097:blood; D001422:Bacterial Adhesion / Q000187:drug effects; D002995:Clofibric Acid / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004926:Escherichia coli / Q000187:drug effects* / Q000276:immunology / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000517:prevention & control*; D004976:Ethacrynic Acid / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D010861:Fimbriae, Bacterial / Q000187:drug effects; D007668:Kidney / Q000382:microbiology / Q000473:pathology; D008565:Membrane Proteins / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D011704:Pyelonephritis / Q000382:microbiology / Q000517:prevention & control*; D014552:Urinary Tract Infections / Q000382:microbiology / Q000517:prevention & control*; D014556:Urine / Q000382:microbiology
D000900:Anti-Bacterial Agents; D000907:Antibodies, Bacterial; D008565:Membrane Proteins; D002995:Clofibric Acid; D004976:Ethacrynic Acid