Effects of Lead Exposure on Ferroptosis Pathway

July 19, 2023 updated by: WenJing Zhao, Northern Jiangsu Province People's Hospital

Effects of Lead Exposure on Iron Metabolism and the Nrf2-dependent Ferroptosis Pathway

The aim of this study was to investigate the effects of chronic lead exposure on iron metabolism and the Nrf2-dependent ferroptosis pathway in lead acid battery factory workers

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Background:

Lead (Pb) is a prevalent and highly toxic heavy metal. Human activities have been the primary cause of lead contamination in the environment over the past century. Lead exposure poses a global concern, particularly for children, and individuals can be exposed to lead through various means, such as contaminated soil, dust, food, water, or foreign objects. The central nervous system (CNS) is particularly vulnerable to the toxic effects of lead (Pb), especially in children, primarily due to the immaturity of the blood-brain barrier.

Ferroptosis is a recently defined form of regulated cell death characterized by iron-dependent cell death resulting from the accumulation of lipid hydroperoxides. However, the exact mechanism underlying the neurotoxic effects of chronic low-level lead exposure-induced ferroptosis on neuronal injury is not yet fully understood.

Methods:

The investigators first analyze the difference of blood lead level using atomic absorption spectrometry.

The investigators enrolled 20 chronic lead exposure workers from a lead acid battery factory and an age-matched control group of non-lead-exposed workers.

TNF-α elisa kit was used to compare the proinflammatory cytokines in two groups.

Quantitative reverse transcription PCR (Polymerase Chain Reaction) was used to compare messenger ribonucleic acid (mRNA) expression of iron metabolism (FTH1, FPN1, DMT1) and the Nrf2-dependent ferroptosis pathway (Nrf2, SLC7A11, GPX4)

Detailed Methods protocol

  1. The criteria of enrolled chronic lead exposure participants were as follows：inclusion: work for this lead acid battery factory more than 10 year; exclusion: exposure to any chemistry pollution before; neurological disorders; endocrine diseases; cancer
  2. Sample collection: at the end of recruitment in this study, all of the enrolled participant will come to the hospital to collect peripheral Blood (Northern Jiangsu People's Hospital, affiliated with Yangzhou University), and the blood samples will be collected into EDTA (ethyleneDiamine tetraacetic acid) vacutainer tubes and then divided into leukocytes and plasma for further experiments.
  3. TNF-α ELISA KIT: Plasma TNF-α concentrations were detected by the competitive ELISA method
  4. Primer sequence used in this study:

1.DMT1 forward: 5'-CTAGACTGGGAGTGGTTACTGG-3' DMT1 reverse: 5'-AGGATGACTCGTGGGACCTT-3' 2.FTH1 forward: 5'-CTGGTGGCCGAATCTTCCTTCA-3' FTH1 reverse: 5'-GCCAGTTTGTGCAGTTCCAG-3' 3.FPN1 forward: 5'-CTACTTGGGGAGATCGGATGT-3' FPN1 reverse: 5'-CTGGGCCACTTTAAGTCTAGC-3' 4.GPX4 forward: 5'-GAGGCAAGACCGAAGTAAACTAC-3' GPX4 reverse: 5'-CCGAACTGGTTACACGGGAA-3' 5.SLC7A11 forward: 5'-TCTCCAAAGGAGGTTACCTGC-3' SLC7A11 reverse: 5'-AGACTCCCCTCAGTAAAGTGAC-3' 6. Nrf2 forward 5'-ATAGCTGAGCCCAGTATC-3' Nrf2 reverse 5'- CATGCACGTGAGTGCTCT-3' 7. GAPDH forward: 5'-GGAGCGAGATCCCTCCAAAAT-3' GAPDH reverse: 5'-GGCTGTTGTCATACTTCTCATGG-3'

Study Type

Observational

Enrollment (Estimated)

40

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Jiangsu
      • Yangzhou, Jiangsu, China, 225001
        • Recruiting
        • Wenjing Zhao
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

The control group will be selected from the invited who live in Yangzhou city via the website, email, and poster.

The lead exposure group will be selected from the invited volunteers who live in Yangzhou with the assistance of the Center for Disease Control and Prevention of Yangzhou, the website, email, and poster.

Description

Inclusion Criteria:

  1. Aged over 18 years old
  2. Work for the lead acid battery factory more than 10 years

Exclusion Criteria:

  1. Neurological disorders
  2. Endocrine diseases
  3. Cancer
  4. Exposure to any chemical pollutant before

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
The control group
The invited non-lead-exposed workers live in Yangzhou, Jiangsu, China
The lead exposure group
The invited chronic-lead exposed workers live in Yangzhou, Jiangsu, China
Other: Lead exposure
The lead-acid battery factory workers will exposure to lead via Inhalation of lead particles, ingestion of lead-contaminated dust and water.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Concentration of TNF-α level in peripheral blood
Time Frame: From the date of all participants documented baseline data, until the date of the last participant documented the changes of biomarkers in peripheral blood, assessed up to 60 days
Biomarkers of the proinflammatory cytokines
From the date of all participants documented baseline data, until the date of the last participant documented the changes of biomarkers in peripheral blood, assessed up to 60 days
The relative mRNA expression rate of the Nrf2- dependent ferroptosis genes in peripheral blood
Time Frame: From the date of all participants documented baseline data, until the date of the last participant documented the changes of biomarkers in peripheral blood, assessed up to 60 days
Biomarkers of the Nrf2- dependent ferroptosis
From the date of all participants documented baseline data, until the date of the last participant documented the changes of biomarkers in peripheral blood, assessed up to 60 days
The relative mRNA expression rate of the iron metabolism genes in peripheral blood
Time Frame: From the date of all participants documented baseline data, until the date of the last participant documented the changes of biomarkers in peripheral blood, assessed up to 60 days
Biomarkers of the iron metabolism
From the date of all participants documented baseline data, until the date of the last participant documented the changes of biomarkers in peripheral blood, assessed up to 60 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Northern Jiangsu Province People's Hospital

Collaborators

Centers for Disease Control and Prevention

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2023

Primary Completion (Estimated)

August 10, 2023

Study Completion (Estimated)

September 25, 2023

Study Registration Dates

First Submitted

July 11, 2023

First Submitted That Met QC Criteria

July 11, 2023

First Posted (Actual)

July 18, 2023

Study Record Updates

Last Update Posted (Actual)

July 21, 2023

Last Update Submitted That Met QC Criteria

July 19, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Lead exposure

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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