(1) chelatable iron can fully account for heme protein-triggered proximal tubular injury; (2) HO contributes to this injury, presumably by causing iron release; (3) the heme-induced injury appears to be mediated by non-.OH oxidizing intermediates; (4) GSH can exert both anti- and pro-oxidant effects; and (5) i.m. glycerol injection, followed by proximal tubular isolation, represents a new and highly useful model for studying direct determinants of heme protein cytotoxicity.

(1) sphingosine and ceramide fluxes are hallmarks of early ischemic/reperfusion injury; (2) these changes occur via divergent metabolic pathways; and (3) that ceramide increments can affect divergent injury pathways, and that sphingosine and ceramide have potent cell signaling effects, suggest that the currently documented sphingosine/ ceramide fluxes could have important implications for the induction phase and evolution of post-ischemic ARF.

Isoflurane profoundly and differentially affects tubular cell responses to toxic and hypoxic attack. Direct drug-induced alterations in lipid trafficking/plasma membrane orientation and in cell energy production are likely involved. Although the in vivo relevance of these findings remains unknown, they have potential implications for intraoperative renal tubular cell structure/function and how cells may respond to superimposed attack.