Effects of Lead Exposure on Ferroptosis Pathway

Neurotoxicity Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05950386
• Other study ID #: Lead exposure
• Status: Recruiting
• Start date: July 1, 2023
• Est. completion date: September 25, 2023

Study information

• Verified date: July 2023
• Source: Northern Jiangsu Province People's Hospital
• Contact: Ju Gao
• Phone: +8618118206088
• Email: gaoju_003[@]163.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

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'

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: September 25, 2023
• Est. primary completion date: August 10, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Lead Poisoning
• Neurotoxicity
• Neurotoxicity Syndromes
• Poisoning

Intervention

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.

Locations

Country	Name	City	State
China	Wenjing Zhao	Yangzhou	Jiangsu

Sponsors (2)

Lead Sponsor	Collaborator
Northern Jiangsu Province People's Hospital	Centers for Disease Control and Prevention

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Concentration of TNF-a level in peripheral blood	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
Primary	The relative mRNA expression rate of the Nrf2- dependent ferroptosis genes in peripheral blood	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
Primary	The relative mRNA expression rate of the iron metabolism genes in peripheral blood	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