Minocycline inhibits apoptosis and inflammation in a rat model of ischemic renal injury

Katherine Kelly, Timothy Sutton, N. Weathered, N. Ray, E. J. Caldwell, Z. Plotkin, Pierre Dagher

Research output: Contribution to journalArticle

97 Citations (Scopus)

Abstract

Tetracyclines exhibit significant antiinflammatory properties in a variety of rheumatologic and dermatologic conditions. They have also been shown to inhibit apoptosis in certain neurodegenerative disorders. Because ischemic renal injury is characterized by both apoptosis and inflammation, we investigated the therapeutic potential of tetracyclines in a rat model of renal ischemia-reperfusion. Male Sprague-Dawley rats underwent bilateral renal artery clamp for 30 min followed by reperfusion and received either minocycline or saline for 36 h before ischemia. Minocycline reduced tubular cell apoptosis 24 h after ischemia as determined by terminal transferase-mediated dUTP nick end-labeling staining and nuclear morphology. It also decreased cytochrome c release into the cytoplasm and reduced upregulation of p53 and Bax after ischemia. The minocycline-treated group showed a significant reduction in tubular injury and cast formation. In addition, minocycline reduced the number of infiltrating leukocytes, decreased leukocyte chemotaxis both in vitro and ex vivo, and downregulated the expression of ICAM-1. Serum creatinine 24-h postischemia was significantly reduced in the minocycline-treated group. We conclude that minocycline has potent antiapoptotic and anti-inflammatory properties and protects renal function in this model of ischemia-reperfusion. Tetracyclines are among the safest and best-studied antibiotics. They are thus attractive candidates for the therapy of human ischemic acute renal failure.

Original languageEnglish
JournalAmerican Journal of Physiology - Renal Physiology
Volume287
Issue number4 56-4
DOIs
StatePublished - Oct 2004

Fingerprint

Minocycline
Apoptosis
Inflammation
Kidney
Ischemia
Tetracyclines
Wounds and Injuries
Reperfusion
Anti-Inflammatory Agents
Leukocyte Chemotaxis
Renal Artery
Intercellular Adhesion Molecule-1
Transferases
Cytochromes c
Leukocyte Count
Acute Kidney Injury
Neurodegenerative Diseases
Sprague Dawley Rats
Creatinine
Cytoplasm

Keywords

  • Acute renal failure
  • Cytochrome c
  • P53
  • Tetracyclines

ASJC Scopus subject areas

  • Physiology

Cite this

Minocycline inhibits apoptosis and inflammation in a rat model of ischemic renal injury. / Kelly, Katherine; Sutton, Timothy; Weathered, N.; Ray, N.; Caldwell, E. J.; Plotkin, Z.; Dagher, Pierre.

In: American Journal of Physiology - Renal Physiology, Vol. 287, No. 4 56-4, 10.2004.

Research output: Contribution to journalArticle

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