Prolonged Pulmonary Exposure to Diesel Exhaust Particles Exacerbates Renal Oxidative Stress, Inflammation and DNA Damage in Mice with Adenine-Induced Chronic Renal Failure

Cell Physiol Biochem. 2016;38(5):1703-13. doi: 10.1159/000443109. Epub 2016 May 3.

Abstract

Background/aims: Epidemiological evidence indicates that patients with chronic kidney diseases have increased susceptibility to adverse outcomes related to long-term exposure to particulate air pollution. However, mechanisms underlying these effects are not fully understood.

Methods: Presently, we assessed the effect of prolonged exposure to diesel exhaust particles (DEP) on chronic renal failure induced by adenine (0.25% w/w in feed for 4 weeks), which is known to involve inflammation and oxidative stress. DEP (0.5m/kg) was intratracheally (i.t.) instilled every 4th day for 4 weeks (7 i.t. instillation). Four days following the last exposure to either DEP or saline (control), various renal endpoints were measured.

Results: While body weight was decreased, kidney weight increased in DEP+adenine versus saline+adenine or DEP. Water intake, urine volume, relative kidney weight were significantly increased in adenine+DEP versus DEP and adenine+saline versus saline. Plasma creatinine and urea increased and creatinine clearance decreased in adenine+DEP versus DEP and adenine+saline versus saline. Tumor necrosis factor α, lipid peroxidation and reactive oxygen species were significantly increased in adenine+DEP compared with either DEP or adenine+saline. The antioxidant calase was significantly decreased in adenine+DEP compared with either adenine+saline or DEP. Notably, renal DNA damage was significantly potentiated in adenine+DEP compared with either adenine+saline or DEP. Similarly, systolic blood pressure was increased in adenine+DEP versus adenine+saline or DEP, and in DEP versus saline. Histological evaluation revealed more collagen deposition, higher number of necrotic cell counts and dilated tubules, cast formation and collapsing glomeruli in adenine+DEP versus adenine+saline or DEP.

Conclusion: Prolonged pulmonary exposure to diesel exhaust particles worsen renal oxidative stress, inflammation and DNA damage in mice with adenine-induced chronic renal failure. Our data provide biological plausibility that air pollution aggravates chronic renal failure.

MeSH terms

  • Adenine / toxicity
  • Animals
  • Antioxidants / metabolism
  • Blood Pressure / drug effects
  • Body Weight / drug effects
  • Catalase / metabolism
  • Creatinine / blood
  • DNA Damage / drug effects*
  • Female
  • Inflammation
  • Kidney / drug effects
  • Kidney / pathology
  • Kidney Failure, Chronic / etiology
  • Kidney Failure, Chronic / metabolism
  • Kidney Failure, Chronic / pathology
  • Lipid Peroxidation / drug effects
  • Male
  • Mice
  • Oxidative Stress / drug effects*
  • Particulate Matter / toxicity*
  • Reactive Oxygen Species / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Urea / blood
  • Vehicle Emissions

Substances

  • Antioxidants
  • Particulate Matter
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • Vehicle Emissions
  • Urea
  • Creatinine
  • Catalase
  • Adenine