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Examination of the Exposome in an Animal Model: The Impact of High-Fat Diet and Rat Strain on Local and Systemic Immune Markers Following Occupational Welding Fume Exposure

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  • Description:
    An experimental model was designed to investigate the impact of multiple exposomal factors on susceptibility to acute lung toxicity and subsequent resolution of inflammation following an occupationally-relevant inhalation exposure. To assess the role of genetic influence, two rat strains-Sprague-Dawley (SD) and Brown Norway (BN)-were used. A high fat (HF) "Western diet" (14.8% protein, 40.6% carbohydrate, 44.6% fat) was also incorporated to evaluate the potential impact of behavioral/lifestyle factors. Accordingly, male SD and BN rats were maintained on a HF or regular (Reg) diet for 24 wks. Inhalation exposure to filtered air or stainless steel welding fume (WF; 53% Fe, 24% Mn, 17% Cr, 6% Ni, 0.4% Cu) occurred beginning wk 7 for 5 wks (target concentration of 20 mg/m3 × 3 h/day × 4 days/week × 5 weeks). Rats were euthanized at 7, 12, and 24 wks to evaluate local and systemic immune markers corresponding to the baseline, exposure, and recovery phases of the study, respectively. At 7 wks, HF-fed animals exhibited several immune alterations (blood leukocyte/neutrophil number, lymph node B-cell proportionality) with effects more pronounced in SD than BN rats. Indices of acute lung inflammation were elevated in all WF-exposed animals at 12 wks; however, diet appeared to preferentially impact SD rats at this time point, as lymph node cellularity and bronchoalveolar lavage neutrophils were further elevated in HF over Reg animals. Overall, SD rats exhibited the greatest capacity for recovery of altered immune markers to baseline values by 24 wk. In BN rats, resolution of inflammation was further compromised by HF diet, as many exposure-induced alterations in local/systemic immune markers were still evident in HF/WF animals at 24 wks. Collectively, HF diet appeared to have a greater impact on global immune status and acute lung injury in SD rats, but a more pronounced effect on inflammation resolution in BN rats. These results illustrate the potential combined impact of genetic, behavioral, and environmental factors in modulating immunological responsivity and ultimately emphasize the importance of the exposome in shaping biological responses. [Description provided by NIOSH]
  • Subjects:
  • Keywords:
  • ISSN:
    1096-6080
  • Document Type:
  • Genre:
  • Place as Subject:
  • CIO:
  • Division:
  • Topic:
  • Location:
  • Pages in Document:
    83
  • Volume:
    192
  • NIOSHTIC Number:
    nn:20067211
  • Citation:
    Toxicologist 2023 Mar; 192(S1):83
  • Federal Fiscal Year:
    2023
  • Peer Reviewed:
    False
  • Source Full Name:
    The Toxicologist. Society of Toxicology 62nd Annual Meeting & ToxExpo, March 19-23, 2023, Nashville, Tennessee
  • Collection(s):
  • Main Document Checksum:
    urn:sha-512:96671f0aa84178437ea0b896246a6717f908e6bb7d8f2fced1e27548a1b955a49a75e316fe5bda6f49ae15f4509edb3f5d15d72afd4df84d6daf77c6d88c20ea
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  • File Type:
    Filetype[PDF - 1.11 MB ]
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