Date of Award

2026

Document Type

Dissertation

Degree Name

Pharmaceutical Sciences (Ph.D.)

Department

Pharmaceutical Sciences

First Advisor

Joseph M Cerreta

Abstract

Erbium oxide nanoparticles (Er2O3 NPs) are used in various products from simple pottery to semiconductors and such usage leads to an elevated risk of accidental occupational exposure. In the present study, the pulmonary toxicity of Er2O3 NPs was assessed by examining tissues and bronchoalveolar lavage fluid (BALF) from the lungs of Golden Syrian Hamsters following inhalation exposure. The study’s goal was to determine the severity and mechanism of toxicity upon exposure to inhaled Er2O3 NPs. Animals were divided into 4 groups all being exposed for 4 hours a day for 8 days: Group-1: room air, Group-2: vehicle control (water), Group-3: exposed to 5 mg/m3 of Er2O3 NPs, and Group-4: exposed to 10 mg/m3 of Er2O3 NPs. Following exposure, the BALFs were assessed for lactate dehydrogenase (LDH), alkaline phosphatase (ALP) activity and by a differential cell count. There were significant increases in the LDH and ALP activity in the BALF in the treated groups 3 and 4 when compared to the levels from control groups 1 and 2, indicating cytotoxicity. There were significant increases in total cell counts, especially of neutrophils. To determine the mechanism of toxicity, TUNEL positive cells were counted and protein levels of biomarkers pertaining to apoptosis, autophagy, pyroptosis and necroptosis were evaluated. There was a significant increase of TUNEL positive cells in the treated groups 3 and 4 when compared to control groups 1 and 2, indicating potentially apoptotic or necrotic cell death. The western blot analyses indicated that apoptosis, pyroptosis and necroptosis were not activated to completion, while autophagy was initiated but interrupted. Electron microscopy showed morphological changes in type II pneumocytes, alternations to airway epithelium and internalization of nanoparticles. The results from this study indicate that exposure to Er2O3 NPs can cause autophagic flux to be interrupted, leading to cytotoxic effects with lysosomal disruption and lung injury.

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