Protective effect of carbon monoxide-releasing compounds in ischemia-induced acute renal failure.
Heme oxygenase (HO) induction has been demonstrated to be beneficial in limiting the extent of cellular damage after ischemia-induced acute renal failure (ARF). Because increased HO activity is associated with the production of carbon monoxide (CO) as well as the potent antioxidant bilirubin, it is unclear which of the two is of greater importance in the protective effects of HO induction. The purpose of this study was to determine the protective role of CO alone in ischemia-induced ARF. Bilateral clamping of the renal pedicle for 40 min was associated with a ninefold increase in the levels of plasma creatinine 24 h after reperfusion as compared with normal plasma creatinine levels; however, administration of CO donor compounds tricarbonyldichlororuthenium(II) dimer, ([Ru(CO)(3)Cl(2)](2), 10 mg/kg) or tricarbonylchloro(glycinato)ruthenium(II) ([Ru(CO)(3)Cl(glycinate)], (CORM-3) 1 h before the onset of ischemia significantly decreased the levels of plasma creatinine 24 h after reperfusion as compared with vehicle-treated mice. Surprising, treatment with the CO donors was associated with an increase in HO activity 24 h after ischemia. For determining whether the protective effects of the CO donors were due to CO or HO-1 induction, experiments were performed in which HO was inhibited before administration of the CO donors. Pretreatment with the HO inhibitor had no effect on the level of plasma creatinine 24 h after reperfusion after treatment with the CO donor compounds. These results suggest that CO itself may be protective and limit renal damage in ischemia induced ARF.
Vera
Trinity
T
Department of Physiology and Biophysics, Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4505, USA.
Henegar
Jeffery R
JR
Drummond
Heather A
HA
Rimoldi
John M
JM
Stec
David E
DE
D058186:Acute Kidney Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D002248:Carbon Monoxide / Q000378:metabolism*; D003404:Creatinine / Q000097:blood; D019610:Cytoprotection; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000378:metabolism; D051547:Heme Oxygenase-1; D007511:Ischemia / Q000097:blood / Q000150:complications* / Q000201:enzymology; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D009942:Organometallic Compounds / Q000494:pharmacology*; D013997:Time Factors; D015032:Zinc / Q000494:pharmacology
D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D009942:Organometallic Compounds; C476530:tricarbonylchloro(glycinato)ruthenium(II); C447082:tricarbonyldichlororuthenium (II) dimer; D002248:Carbon Monoxide; D003404:Creatinine; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D015032:Zinc