Effects of early life heavy metal exposure on the metabolome of mouse lungs Open Access
Xu, Lennox (Spring 2023)
Published
Abstract
Heavy metal exposure from metals like cadmium and arsenic in fetal development and early life hurts the development of lungs and leads to decreased lung functioning. Previous work has shown that cadmium (Cd) and arsenic (As) at levels similar to non-occupational human exposures via everyday exposures, such as drinking water, can lead to postnatal lung function alterations and susceptibility to lung and airway disease. Additionally, these effects are greatly worsened by a combination of both low-level Cd and As. We aim to determine the exact mechanistic effects of the early life exposure to heavy metals by examining changes in the metabolome. We performed mass spectrometry and metabolomic analysis on early postnatal pups after they were exposed to Cd and As in utero. The dams were provided with low levels and high levels of Cd and As (50 and 250 ppb, respectively, each) in drinking water and purified AIN-93G diet ad libitum for 10 weeks prior to breeding and continued until 3 weeks postpartum, exposing the pups to heavy metals during pregnancy and lactation. The exposed postnatal pup lungs were processed for metabolite quantification with an Orbitrap mass spectrometer. High resolution metabolomics was used to study metabolic changes and discover disease biomarkers. Our results have shown significant changes in various pathways vital for the development of lungs, as well as changes in the inflammation pathway. The regulation of the arachidonic acid inflammation metabolism pathway is especially essential in maintaining a balance between beneficial and harmful inflammation. The significant changes we have seen in this path, as well as the prevalence of heavy metal exposure in the everyday life of the world population, make this field of research a very important area of study. Ultimately, this research presents potential metabolites to focus on in the future for anti-inflammatory drugs to target and regulate the production for during the early life. There is hope that this would then lessen the risk of long term negative health consequences of heavy metals.
Table of Contents
Tables of Contents
Introduction……………….…………………………………………………………………..….1
Background………………………………………………………………………………………..3
Cadmium and Arsenic
Mouse Model
Mass Spectroscopy
Metabolomics
Inflammation
Methods………………………………………………………………………………………….14
Experiment
Metabolomics
Results………………..…………………………………………………………………………..18
Discussion.……………………………………………………………………………………….22
Figures and Tables….....………………………...…………………………………………...26
References………………….…………………………………………………………………….41
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Effects of early life heavy metal exposure on the metabolome of mouse lungs () | 2023-04-10 02:01:19 -0400 |
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