title: Anomalous renal effects of tin protoporphyrin in a murine model of sickle cell disease.
abstract: In human and murine models of sickle cell disease (SCD), heme oxygenase-1 (HO-1) is induced in the kidney, an organ commonly involved in SCD. The present study assessed the role of HO-1 by using a competitive inhibitor of HO activity, tin protoporphyrin (SnPP), in protocols affording a composite, clinically relevant analysis of the kidney in SCD under unstressed and stressed conditions. Whereas short-term administration of SnPP exerted comparable renal hemodynamic effects in wild-type and sickle mice, chronic administration of SnPP exerted divergent effects: SnPP provoked tubulointerstitial inflammation and up-regulation of injury-related genes in wild-type mice, whereas in sickle mice SnPP reduced expression of injury-related genes and vascular congestion without provoking tubulointerstitial inflammation. SnPP also protected against the heightened sensitivity to renal ischemia observed in sickle mice, preventing ischemia-induced worsening of renal injury in sickle mice above that observed in wild-type mice. Effective and comparable inhibition of HO activity by SnPP in wild-type and sickle mice was confirmed. These findings suggest that induction of HO-1, at least as assessed by this approach, may contribute to renal injury in this murine model of SCD and uncover an experimental maneuver that protects the kidney in murine SCD.
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
authors.forename: Julio P
authors.initials: JP
authors.lastname: Juncos
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Grande
authors.forename: Narayana
authors.initials: N
authors.lastname: Murali
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Croatt
authors.forename: Luis A
authors.initials: LA
authors.lastname: Juncos
authors.forename: Robert P
authors.initials: RP
authors.lastname: Hebbel
authors.forename: Zvonimir S
authors.initials: ZS
authors.lastname: Katusic
authors.forename: Karl A
authors.initials: KA
authors.lastname: Nath
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors*; D006450:Hemoglobin SC Disease / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D007674:Kidney Diseases / Q000209:etiology / Q000517:prevention & control*; D007677:Kidney Function Tests; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic; D011524:Protoporphyrins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D015427:Reperfusion Injury; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D008665:Metalloporphyrins; D011524:Protoporphyrins; D012333:RNA, Messenger; C032628:tin protoporphyrin IX; D051547:Heme Oxygenase-1