Aprotinin improves kidney function and decreases tubular cell apoptosis and proapoptotic signaling after renal ischemia-reperfusion

Ajay Kher, Kirstan K. Meldrum, Karen L. Hile, Meijing Wang, Ben M. Tsai, Mark W. Turrentine, John W. Brown, Daniel R. Meldrum

Research output: Contribution to journalArticle

27 Scopus citations


Objective: The purpose of the study was to determine the effects of aprotinin on (1) renal function, (2) apoptosis and apoptotic signaling, and (3) the inflammatory response of the kidney after ischemia-reperfusion injury. Methods: Male rats underwent a sham procedure or left renal ischemia for 1 hour. Rats were divided into three groups and received no reperfusion, reperfusion for 1 hour, or reperfusion for 24 hours. The animals undergoing ischemia received saline solution alone or aprotinin (60,000 kIU/kg). At the end of the experiment, a sample for serum creatinine was taken and the left kidney was harvested. The kidney was analyzed for expression of tumor necrosis factor α, interleukin 1β, and interleukin 6 (enzyme-linked immunosorbent assay and reverse transcriptase-polymerase chain reaction) and activation of p38 mitogen-activated protein kinase, caspase 3, and caspase 8 (Western blot). The kidney was assessed for apoptosis with enzyme-linked immunosorbent assay and by terminal deoxynucleotidyl transferase biotin-deoxyuridine triphosphate nick-end labeling staining of tissue slides. Results: Aprotinin significantly decreased the rise in serum creatinine and apoptosis caused by ischemia-reperfusion. Aprotinin significantly reduced interleukin 1 and 6 messenger RNA production and showed a trend toward reducing tumor necrosis factor messenger RNA production after ischemia. Aprotinin also significantly reduced caspase 8 activation and showed a trend toward decreasing p38 mitogen-activated protein kinase activation after 1 hour of reperfusion. Conclusion: These results suggest that aprotinin provides protection from renal ischemia-reperfusion injury. They also suggest that aprotinin may do so by affecting apoptotic signaling and inflammatory cytokine production. Aprotinin is a potential therapeutic measure in clinical situations where renal ischemia-reperfusion injury can be anticipated, provided adequate heparinization is possible.

Original languageEnglish (US)
Pages (from-to)662.e1-662.e11
JournalJournal of Thoracic and Cardiovascular Surgery
Issue number3
StatePublished - Sep 2005

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

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