Effects of Lead Exposure on Ferroptosis Pathway

Sponsor

Northern Jiangsu Province People's Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT05950386

Collaborator

Centers for Disease Control and Prevention (U.S. Fed)

Enrollment

Location

2.8

Anticipated Duration (Months)

14.2

Patients Per Site Per Month

Study Details

Study Description

Brief 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

Condition or Disease	Intervention/Treatment	Phase
Lead Poisoning Neurotoxicity	Other: Lead exposure

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

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
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.
TNF-α ELISA KIT: Plasma TNF-α concentrations were detected by the competitive ELISA method
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 Design

Study Type:

Observational

Anticipated Enrollment :

40 participants

Observational Model:

Case-Control

Time Perspective:

Cross-Sectional

Official Title:

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

Actual Study Start Date :

Jul 1, 2023

Anticipated Primary Completion Date :

Aug 10, 2023

Anticipated Study Completion Date :

Sep 25, 2023

Arms and Interventions

Arm	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.

Arm

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.

Outcome Measures

Primary Outcome Measures

Concentration of TNF-α level in peripheral blood [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
The relative mRNA expression rate of the Nrf2- dependent ferroptosis genes in peripheral blood [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
The relative mRNA expression rate of the iron metabolism genes in peripheral blood [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