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1 Department of Medicine, Division of Nephrology, Indiana University, Indianapolis, IN, USA
* To whom correspondence should be addressed. E-mail: pdaghe2{at}iupui.edu.
Tetracyclines exhibit significant anti-inflammatory 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 both by 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 hours prior to ischemia. Minocycline reduced tubular cell apoptosis 24 hours after ischemia as determined by TUNEL 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 hours post ischemia was significantly reduced in the minocycline - treated group. We conclude that minocycline has potent anti-apoptotic and antiinflammatory properties and protects renal function in this model of ischemiareperfusion. Tetracyclines are among the safest and best studied antibiotics. They are thus attractive candidates for the therapy of human ischemic acute renal failure.
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