Abstract

Renal ischemia is a major cause of acute renal failure. Ulinastatine (UTI), a protease inhibitor, has been reported to help protect against ischemia and various types of shock; however, its mechanism for these protective effects is not fully known. We have investigated the effects of UTI on renal ischemia and reperfusion by measuring the tissue pO2 simultaneously in the renal cortex and medulla in rats. The principal experimental protocol was 30 min renal ischemia (by clamping the abdominal aorta) followed by 60 min reperfusion. Treatments were 0.9%NaCl 1ml/kg (NS group) or UTI 50000U/1ml/kg (UTI group) administered 30 min before ischemia. In the NS group, the control pO2 values of renal cortex and medulla were 11.7 +/- 2.3 and 14.4 +/- 5.7 mmHg respectively, whereas those in the UTI group were 18.9 +/- 4.0 and 24.5 +/- 4.2 mmHg. The pO2 of the cortex and medulla decreased to less than 2 mmHg during ischemia in both groups. At 60 min after reperfusion, the pO2 values in NS group were not fully restored (7.6 +/- 2.3 and 6.9 +/-1.4 mmHg), whereas those in the UTI group were completely restored to the control value (21.1 +/-4.8 and 25.5 +/- 2.1 mmHg) . These data indicate that administration of UTI before ischemia increases the renal cortical and medullary pO2 after reperfusion.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR011602-05
Application #
6353202
Study Section
Project Start
2000-09-01
Project End
2002-04-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
5
Fiscal Year
2000
Total Cost
$12,155
Indirect Cost

  Institution

Name
Dartmouth College
Department
Type
DUNS #
041027822
City
Hanover
State
NH
Country
United States
Zip Code
03755

  Publications

Sinha, Birandra K; Leinisch, Fabian; Bhattacharjee, Suchandra et al. (2014) DNA cleavage and detection of DNA radicals formed from hydralazine and copper (II) by ESR and immuno-spin trapping. Chem Res Toxicol 27:674-82
Dunn, Jeff F; Khan, Mohammad N; Hou, Huagang G et al. (2011) Cerebral oxygenation in awake rats during acclimation and deacclimation to hypoxia: an in vivo electron paramagnetic resonance study. High Alt Med Biol 12:71-7
Chen, Bin; Pogue, Brian W; Goodwin, Isak A et al. (2003) Blood flow dynamics after photodynamic therapy with verteporfin in the RIF-1 tumor. Radiat Res 160:452-9
Dunn, Jeff F; Swartz, Harold M (2003) In vivo electron paramagnetic resonance oximetry with particulate materials. Methods 30:159-66
Khan, Nadeem; Shen, Jiangang; Chang, Ta Yuan et al. (2003) Plasma membrane cholesterol: a possible barrier to intracellular oxygen in normal and mutant CHO cells defective in cholesterol metabolism. Biochemistry 42:23-9
Shen, Jiangang; Khan, Nadeem; Lewis, Lionel D et al. (2003) Oxygen consumption rates and oxygen concentration in molt-4 cells and their mtDNA depleted (rho0) mutants. Biophys J 84:1291-8
Khan, Nadeem; Wilmot, Carmen M; Rosen, Gerald M et al. (2003) Spin traps: in vitro toxicity and stability of radical adducts. Free Radic Biol Med 34:1473-81
Pogue, Brian W; O'Hara, Julia A; Demidenko, Eugene et al. (2003) Photodynamic therapy with verteporfin in the radiation-induced fibrosarcoma-1 tumor causes enhanced radiation sensitivity. Cancer Res 63:1025-33
Hou, Huagang; Grinberg, Oleg Y; Taie, Satoshi et al. (2003) Electron paramagnetic resonance assessment of brain tissue oxygen tension in anesthetized rats. Anesth Analg 96:1467-72, table of contents
Swartz, Harold M (2002) Measuring real levels of oxygen in vivo: opportunities and challenges. Biochem Soc Trans 30:248-52

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