Anomalous renal effects of tin protoporphyrin in a murine model of sickle cell disease

Julio P. Juncos, Joseph Peter Grande, Narayana Murali, Anthony J. Croatt, Luis A. Juncos, Robert P. Hebbel, Zvonimir S Katusic, Karl A Nath

Research output: Contribution to journalArticle

18 Citations (Scopus)

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 tubulo-interstitial 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 con-firmed. 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.

Original languageEnglish (US)
Pages (from-to)21-31
Number of pages11
JournalAmerican Journal of Pathology
Volume169
Issue number1
DOIs
StatePublished - Jul 2006

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Sickle Cell Anemia
Kidney
Heme Oxygenase-1
Wounds and Injuries
Ischemia
Inflammation
tin protoporphyrin IX
Genes
Blood Vessels
Up-Regulation
Hemodynamics

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Anomalous renal effects of tin protoporphyrin in a murine model of sickle cell disease. / Juncos, Julio P.; Grande, Joseph Peter; Murali, Narayana; Croatt, Anthony J.; Juncos, Luis A.; Hebbel, Robert P.; Katusic, Zvonimir S; Nath, Karl A.

In: American Journal of Pathology, Vol. 169, No. 1, 07.2006, p. 21-31.

Research output: Contribution to journalArticle

Juncos, Julio P. ; Grande, Joseph Peter ; Murali, Narayana ; Croatt, Anthony J. ; Juncos, Luis A. ; Hebbel, Robert P. ; Katusic, Zvonimir S ; Nath, Karl A. / Anomalous renal effects of tin protoporphyrin in a murine model of sickle cell disease. In: American Journal of Pathology. 2006 ; Vol. 169, No. 1. pp. 21-31.
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