Respirable ambient particulate matter (PM) exposure has been associated with an increased risk of cardiovascular disease. Direct translocation of PM-associated metals from the lungs into systemic circulation may be partly responsible. We measured elemental content of lungs, plasma, heart, and liver of healthy male WKY rats (12-15 weeks old) 4 or 24 h following a single intratracheal (IT) instillation of saline or 8.33 mg/kg of oil combustion PM (HP-12) containing a variety of transition metals with differing water and acid solubility. Tissues were digested with a combination of quaternary acid, amine, and nitric acid and analyzed using inductively coupled plasma-atomic emission spectroscopy. Lung levels of metals were lower at 24 h than at 4 h. Metals with high water solubility and relatively high concentration in HP-12 were increased in extrapulmonary organs. Water-soluble nonessential metals, like vanadium and nickel, were increased in plasma, hearts, and livers of exposed animals at both time points. Exposure-related small increases in essential metals, like zinc and manganese, were also noted in extrapulmonary tissues at both time points. Lead, with low water solubility but high acid solubility, was detected in liver only at 24-h postinstillation. Elements with low water or acid solubility, like silicon and aluminum, were not detected in extrapulmonary tissues despite decreased levels in the lung suggesting mucociliary clearance. We have shown that HP-12-associated metals translocate to systemic circulation and extrapulmonary organs following IT exposure. This translocation is dependent upon their relative levels and water solubility. Thus, following inhalation, PM-associated metals deposited in the lung may be released into systemic circulation at different rates depending on their water/acid solubility, thereby providing a means by which metals may elicit direct extrapulmonary effects.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1093/toxsci/kfm088 | DOI Listing |
Int J Pharm
January 2025
Laboratory of Biotherapy, National Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Renmin Nanlu 17, Chengdu 610041, Sichuan, China. Electronic address:
Lipid nanoparticles (LNPs) are among the most promising non-viral mRNA delivery systems for gene therapeutic applications. However, the in vivo delivery of LNP-mRNA remains challenging due to multiple intrinsic barriers that hinder LNPs from reaching their target cells. In this study, we sought to enhance LNP delivery by manipulating intrinsic regulatory mechanisms involved in their metabolism.
View Article and Find Full Text PDFElife
January 2025
Neurobiology and Genetics, Theodor-Boveri-Institute, Biocenter, Julius-Maximilians-University of Würzburg, Würzburg, Germany.
Insulin plays a key role in metabolic homeostasis. insulin-producing cells (IPCs) are functional analogues of mammalian pancreatic beta cells and release insulin directly into circulation. To investigate the in vivo dynamics of IPC activity, we quantified the effects of nutritional and internal state changes on IPCs using electrophysiological recordings.
View Article and Find Full Text PDFTher Deliv
January 2025
Institute of Pharmaceutical Research, GLA University, Mathura, India.
Aim: Development and optimization of raloxifene hydrochloride loaded lipid nanocapsule hydrogel for transdermal delivery.
Method: A 3 Box-Behnken Design and numerical optimization was performed to obtain the optimized formulation. Subsequently, the optimized raloxifene hydrochloride loaded lipid nanocapsule was developed using phase inversion temperature and characterized for physicochemical properties.
Diabetologia
January 2025
Department of Ophthalmology and Visual Sciences, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Aims/hypothesis: Within the small intestine, neutrophils play an integral role in preventing bacterial infection. Upon interaction with bacteria or bacteria-derived antigens, neutrophils initiate a multi-staged response of which the terminal stage is NETosis, formation of protease-decorated nuclear DNA into extracellular traps. NETosis has a great propensity to elicit ocular damage and has been associated with diabetic retinopathy and diabetic macular oedema (DME) progression.
View Article and Find Full Text PDFmSphere
January 2025
Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa, USA.
Visceral leishmaniasis (VL) is a vector-borne disease caused by the obligate intracellular protozoan in India. VL can be complicated by post-kala-azar dermal leishmaniasis (PKDL), a macular or nodular rash that develops in 10%-20% of patients after treatment of VL in India. Patients with PKDL are infectious to sand flies, promoting further transmission of the parasite.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!