Leupeptin-mediated alteration of renal phagolysosomes: similarity to hyaline droplet nephropathy of male rats exposed to unleaded gasoline

Michael J. Olson, Michael A. Mancini, Bhagwan D. Garg, Arun K. Roy

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

α2u-Globulin, a protein of hepatic origin found in the urine of male rats, is accumulated in the kidney cortex during exposure to unleaded gasoline and has been implicated in the development of fuel hydrocarbon-induced nephropathy and renal neoplasia. The principal morphological feature of gasoline-induced nephropathy is accumulation of hyaline droplets (enlarged secondary lysosomes or phagolysosomes) in epithelial cells of the proximal convoluted tubule S1 and S2 segments. Inhibition of cathepsin B (a major lysosomal peptidase) by treatment of male rats with leupeptin causes rapid accumulation of phagolysosomes and α2u-globulin in the kidney very similar to gasoline exposure. Further, the renal cortical subcellular distribution of α2u-globulin, determined with an electron microscopic immunochemieal method, is almost totally confined to phagolysosomes following administration of either gasoline or leupeptin. These results, taken together, indicate that the mechanism of nephrotoxicity of gasoline involves inhibition of renal phagolysosomal proteolysis.

Original languageEnglish (US)
Pages (from-to)245-254
Number of pages10
JournalToxicology Letters
Volume41
Issue number3
DOIs
StatePublished - Jun 1988
Externally publishedYes

Keywords

  • Gasoline
  • Hyaline droplet nephropathy
  • Leupeptin
  • Phagolysosomes

ASJC Scopus subject areas

  • Toxicology

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