Diesel exhaust particles in the lung aggravate experimental acute renal failure

Toxicol Sci. 2010 Jan;113(1):267-77. doi: 10.1093/toxsci/kfp222. Epub 2009 Oct 1.


Inhaled particles are associated with pulmonary and extrapulmonary effects. Also, acute renal failure (ARF) is associated with increased mortality, related to pulmonary complications. Here, we tested the possible potentiating effect of diesel exhaust particles (DEP) in an animal model of ARF induced by a single ip injection of cisplatin (CP, 6 mg/kg) in rats. Six days later, the rats were intratracheally instilled with either DEP (0.5 or 1 mg/kg) or saline (control) and renal, systemic, and pulmonary variables were studied 24 h thereafter. CP increased the serum concentrations of urea and creatinine and reduced glutathione (GSH) concentration and superoxide dismutase activity in renal cortex. CP caused renal tubular necrosis; increased urine volume, protein concentrations, and N-acetyl-beta-D-glucosaminidase (NAG) activity; and decreased urine osmolality. The combination of DEP and CP aggravated the CP-induced effects on serum urea and creatinine, urine NAG activity, and renal GSH. The arterial O(2) saturation and PO(2) were significantly decreased in CP + DEP versus CP + saline and CP + DEP versus DEP. The number of platelets was reduced in DEP compared to saline-treated rats and CP + DEP versus DEP alone or CP + saline. Increases in macrophage and neutrophils numbers in bronchoalveolar lavage were found in DEP versus saline group and CP + DEP versus CP. Histopathological changes in lungs of DEP-treated rats were aggravated by the combination of CP + DEP. These included marked interstitial cell infiltration and congestion. We conclude that the presence of DEP in the lung aggravated the renal, pulmonary, and systemic effects of CP-induced ARF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosaminidase / urine
  • Acute Kidney Injury / chemically induced*
  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / pathology
  • Animals
  • Biomarkers / blood
  • Biomarkers / urine
  • Blood Platelets / drug effects
  • Bronchoalveolar Lavage Fluid / cytology
  • Carbon Dioxide / blood
  • Cisplatin
  • Creatinine / blood
  • Disease Models, Animal
  • Glutathione / metabolism
  • Inhalation Exposure
  • Kidney Cortex / drug effects*
  • Kidney Cortex / metabolism
  • Kidney Cortex / pathology
  • Lung / drug effects*
  • Lung / metabolism
  • Lung / pathology
  • Macrophages, Alveolar / drug effects
  • Male
  • Neutrophils / drug effects
  • Osmolar Concentration
  • Oxygen / blood
  • Particulate Matter / metabolism
  • Particulate Matter / toxicity*
  • Proteinuria / chemically induced
  • Rats
  • Rats, Wistar
  • Superoxide Dismutase / metabolism
  • Urea / blood
  • Vehicle Emissions / toxicity*


  • Biomarkers
  • Particulate Matter
  • Vehicle Emissions
  • Carbon Dioxide
  • Urea
  • Creatinine
  • Superoxide Dismutase
  • Acetylglucosaminidase
  • Glutathione
  • Cisplatin
  • Oxygen