Protection from toxicant-mediated renal injury in the rat with anti-CD54 antibody.

Abstract:

BACKGROUND:The benefit of the potent chemotherapeutic agent cisplatin in treating neoplasms is limited by nephrotoxicity. We tested the hypothesis that CD54 [intercellular adhesion molecule-1 (ICAM-1)] is an important mediator in cisplatin-mediated renal failure. METHODS:The effect of a monoclonal anti-CD54 antibody was evaluated in a rat model of cisplatin toxicity. Renal function, histopathology, renal myeloperoxidase activity, and mortality were determined in the anti-CD54 and placebo groups. RESULTS:Renal CD54 mRNA expression was markedly increased by 24 hours after exposure to cisplatin in mice. An improvement in renal function, mortality, and histological abnormalities was evident in animals exposed to cisplatin and treated with anti-CD54 antibody (mAb). Seven days after the administration of cisplatin, the mean creatinine was 0.65+/-0.05 mg/dl in the rats that received anti-CD54 mAb and 4.76+/-1.42 in control animals (P<0.02). Mortality was lower in experimental animals (0 vs. 29% in control rats seven days following cisplatin, P<0.04). Histological evidence of cell injury was markedly attenuated (P<0.04) in the treated compared with the control rats. CONCLUSION:CD54 may be critical in the pathophysiology of renal injury following cisplatin, perhaps by its effects on leukocyte-endothelial interactions.

journal_name

Kidney Int

journal_title

Kidney international

authors

Kelly KJ,Meehan SM,Colvin RB,Williams WW,Bonventre JV

doi

10.1046/j.1523-1755.1999.00629.x

subject

Has Abstract

pub_date

1999-09-01 00:00:00

pages

922-31

issue

3

eissn

0085-2538

issn

1523-1755

pii

S0085-2538(15)46370-7

journal_volume

56

pub_type

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