Effect of diet-induced obesity on silica-induced pulmonary toxicity in rats

Details

• Personal Author:
  Chen BT ; Frye BL ; Joseph P ; McKinney W ; Sager TM ; Umbright CM
• Description:
  Millions of workers worldwide are exposed to silica, a causative agent for potentially fatal diseases such as silicosis. In addition, whether avoidable lifestyle factors, such as diet-induced obesity, may modify the likelihood of silicosis development is unknown. Therefore, the objective of this study was to determine the effect of diet-induced obesity, if any, on silica-induced pulmonary toxicity in a rat model. Throughout the study, Fischer 344 rats were continuously fed either a regular fat (RFD; 18% kcal as fat) or a high fat (HFD; 60% kcal as fat) diet. Two weeks after starting the study, the rats were exposed to either air or crystalline silica (15 mg/ m3, 6 hours/day, 5 days). Body weights and serum triglyceride levels, indicators of diet-induced obesity, in the HFD rats were higher compared to the RFD rats. At 1 and 3 months post-silica exposure, bronchoalveolar lavage was done and pulmonary toxicity assessed. Pulmonary toxicity parameters including, lactate dehydrogenase (LDH) activity, oxidant production, and cell counts (including infiltrating neutrophils and alveolar macrophages), were assessed. Inflammatory cytokine levels (IL-1beta, IL-10, TNF-alpha, MCP-1, and MIP-2) were also measured. Expression profiling of a panel of ten genes (CCL2, CCL3, CXCL-1, CEACAM 10, LCN 2, MTIA, MMP-12, SLC13A2, SLC26A4, and SOD2), known to be involved in silica-induced pulmonary toxicity, were assessed by real-time PCR. The results showed that silica inhalation resulted in pulmonary toxicity, at both 1 and 3 months post-exposure, as evidenced by enhanced neutrophil infiltration, increased LDH levels, enhanced oxidant production, increased inflammatory cytokine levels, and overexpression of the genes in both RFD and HFD groups. Silica-induced pulmonary toxicity was more pronounced at 3 months post-exposure than 1 month. In addition, the effect of silica inhalation on gene expression and inflammatory cytokine levels was further enhanced, (up to a 21-fold increase in gene expression and 6-fold increase in cytokine levels) especially at 3 months post-exposure in the HFD group compared to the RFD group. In summary, our results indicated that certain early pulmonary toxicity parameters (inflammatory cytokine levels and gene expression) induced by silica inhalation were enhanced by diet-induced obesity in rats. [Description provided by NIOSH]
• Subjects:
  Biological Assay Blood Body Fluids Body Weight Diagnosis Diet Enzymes Genetics Immune System Laboratories Lung Lung Diseases Macrophages Occupational Health Respiratory System Respiratory Tract Diseases Safety Silicon Dioxide Toxicology

  More +
• Keywords:
  Bioassays Body Fluids Body Weight Cellular Effects Crystalline Silica Cytokines Diagnostic Techniques Enzymatic Effects Enzyme Activity Fats Gene Expression Genes Immune Reaction Immune System Inhalation Laboratory Animals Laboratory Testing Lung Disease Neutrophils Obesity Pulmonary Effects Pulmonary System Disorders Serum Cholesterol Silica Silicosis Toxic Effects

  More +
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Maryland ; OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  156
• Issue:
  1
• NIOSHTIC Number:
  nn:20049461
• Citation:
  Toxicologist 2017 Mar; 156(1):328
• CAS Registry Number:
  Quartz (SiO2) (CAS RN 14808-60-7)
• Federal Fiscal Year:
  2017
• NORA Priority Area:
  Manufacturing ; Construction
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 56th Annual Meeting and ToxExpo, March 12-16, 2017, Baltimore, Maryland
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:b8e944ea67f789ef85e0e05fd1592b812a4bd93ff526bffc5d2a12b1c246e592c265743e35a71278ea67bd995b9ff602dc4e49ad8c995e549623faae183eda80
• Download URL:
  https://stacks.cdc.gov/view/cdc/203905/cdc_203905_DS1.pdf
• File Type:
  [PDF - 943.45 KB ]