Relationship between neutrophil-mediated oxidative injury during acute experimental pyelonephritis and chronic renal scarring

Details

Serval ID
serval:BIB_86C98BC1A409
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Relationship between neutrophil-mediated oxidative injury during acute experimental pyelonephritis and chronic renal scarring
Journal
Infection and Immunity
Author(s)
Meylan  P. R., Markert  M., Bille  J., Glauser  M. P.
ISSN
0019-9567
Publication state
Published
Issued date
07/1989
Peer-reviewed
Oui
Volume
57
Number
7
Pages
2196-202
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jul
Abstract
Previous experiments with rats have suggested that pyelonephritic scarring after acute ascending Escherichia coli pyelonephritis partly results from excessive polymorphonuclear leukocyte (PMN) infiltration and activation in the kidney parenchyma. We have studied the role of PMN oxidative metabolism in generating tissue injury during acute pyelonephritis. Rats with acute pyelonephritis were treated with dapsone (25 mg/kg twice daily for 3 days), a compound known to prevent PMN oxidant damage. In vitro, levels of dapsone easily achieved in vivo inhibited myeloperoxidase (MPO)-mediated reactions involving the oxidation of halides to reactive cytotoxic hypohalites (such as MPO-mediated iodination and luminol-enhanced chemiluminescence). In contrast, dapsone had no effect on superoxide production, lysosomal enzyme release, or bacterial killing by activated PMN. In vivo, dapsone treatment had no significant effect on acute pyelonephritis with respect to (i) bacterial counts, (ii) inflammatory swelling, and (iii) PMN infiltration. However, dapsone-treated animals sacrificed 2 months after acute pyelonephritis had a 65% reduction of renal scars when compared with controls. Since dapsone had no antibacterial effect, this protection is compatible with the hypothesis that dapsone prevented oxidant-generated tissue injury due to the extracellular release of the MPO system by activated PMN during acute suppurative pyelonephritis.
Keywords
Acute Disease Animals Chronic Disease Cicatrix/drug therapy/microbiology/*pathology Cytoplasmic Granules/drug effects/metabolism Dapsone/administration & dosage/pharmacology Escherichia coli/drug effects Free Radicals Growth Inhibitors/pharmacology Male Neutrophils/enzymology/metabolism/*pathology Oxygen/*toxicity Peroxidase/physiology Pyelonephritis/drug therapy/microbiology/*pathology Rats Rats, Inbred Strains Superoxides/blood
Pubmed
Web of science
Create date
11/02/2008 13:40
Last modification date
20/08/2019 15:46
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