In Vitro Toxicity Assessment of Spinel Ferrite Nanoparticles and UVB Co-Exposure in Human Epidermal Keratinocytes

Details

• Personal Author:
  Friend S ; Guppi S ; Kisin ER ; Shvedova AA
• Description:
  Background and Purpose: Spinel ferrite nanoparticles (SFNPs) have attracted significant attention due to their unique characteristics that make them promising candidates for diverse applications in biomedicine, water treatment, catalysts, energy fields and industrial electronic devices. However, before these materials can be considered for potential uses, investigation of their toxicity is needed. Additionally, it is important to address the combined effect of SFNPs with ultraviolet light B (UVB) as it is known that UVB-induced skin inflammation contributes to a number of cutaneous diseases. Methods: This study was carried out to assess the ability of two SFNPs, NiFe2O4 and CoFe2O4, alone (1.25-30 µg/ cm2) or in combination with UVB (1-2 kJ/m2) to induce cell cytotoxicity, oxidative stress, inflammation, and DNA damage in human epidermal keratinocytes (HEK). In addition, modes of cell death (apoptosis, necroptosis, ferroptosis) in response to SFNPs alone or with UVB pre-treatment were investigated. It is known that not only apoptosis, the most studied and best characterized programmed cell death, occurs in the HEK after UVB exposure, but ferroptosis, a non-apoptotic programmed cell death promoted by excessive lipid peroxidation, plays a significant role in initiating UVB-induced inflammation in the skin. Using different cell death inhibitors (zVad-fmk, ferrosatatin-1 and necrostatin-1), apoptosis, ferroptosis and necroptosis in SFNPs alone or co-exposed with UVB keratinocytes were evaluated. Results: Exposure to both SFNPs used in the study induced dose-dependent loss of viability, cell damage, ROS accumulation, release of inflammatory mediators, increases in oxidative stress markers and DNA damage. Pre-exposure to UVB caused significant increase in observed responses. Based on the hierarchical clustering analysis of the inflammatory cytokine/chemokine responses, SFNPs pretreated with UVB alone were segregated from UVB control and no UVB exposed samples. IL-8 and RANTES were upregulated in response to SFNPs exposure alone while IL-1β, IL-6 and TNF-a were significantly increased with UVB pre-treatment. Moreover, we have found that all three inhibitors of apoptosis, ferroptosis and necroptosis could prevent cell damage when exposed to SFNPs alone in this study. However, zVad-fmk (zVad), pan-caspase inhibitor, demonstrated the strongest preventive effect when cells were pre-treated by UVB prior to SFNPs exposure. Ferrosatatin-1 (Fer-1) or necrostatin-1 (Necr-1), ferroptosis and necroptosis inhibitors, also rescued a significant percentage of HEK. Further, HEK exposure to SFNPs alone led to generation of lipid peroxidation products (4-hydroxynonenal, 4-HNE), accumulation of intracellular ROS and depletion of glutathione which were inhibited by Fer-1 and zVad but not by Necr-1. UVB co-exposure significantly intensified the effect of SFNPs inhibited by Fer -1 or zVad only. Conclusions: Overall, our data indicate that SFNPs alone or combined with UVB induced oxidative stress, release of inflammatory mediators and DNA damage. Additionally, our results show that following exposure to SFNPs alone or combined with UVB, majority of damaged HEK undergo either caspase- or lipid peroxidation-dependent type of regulated cell death, thus suggesting the involvement of apoptotic and ferroptotic mechanisms. Additional studies are required to better understand the precise molecular mechanisms of programmed cell death induced by SFNPs alone or co-exposed to UVB. [Description provided by NIOSH]
• Subjects:
  Immune System Occupational Health Safety
• Keywords:
  Cell Death DNA Damage Immune Reaction In Vitro Study Nanoparticles Oxidative Stress Ultraviolet Light
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  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
• Pages in Document:
  308-309
• Volume:
  198
• NIOSHTIC Number:
  nn:20069332
• Citation:
  Toxicologist 2024 Mar; 198(S1):308-309
• Federal Fiscal Year:
  2024
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 63rd Annual Meeting & ToxExpo, March 10-14, 2024, Salt Lake City, Utah
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:85cf659b14732b302da9483c7e64a5d46a03f102d832ab4c1a1ef23a5ae2c3319c3bba120f8389835480a6f0d7c9ff4f786938e04508f625898d477aa242b61a
• Download URL:
  https://stacks.cdc.gov/view/cdc/207832/cdc_207832_DS1.pdf
• File Type:
  [PDF - 578.24 KB ]