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Impacts of lead exposure and chelation therapy on bone metabolism during different developmental stages of rats
Yijing Zhang1, Leilei Zhou2, Shufang Li2
1Xinhua Hospital, MOE-Shanghai Key Laboratory of Children's Environmental Health, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China; The International Peace Maternity & Child Health Hospital of China Welfare Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Insights
Lead exposure during early development significantly harms bone metabolism, with effects most pronounced in infancy. Dimercaptosuccinic acid (DMSA) chelation therapy partially reverses these bone changes, showing greatest efficacy when administered early in life.
Area of Science:
- Toxicology
- Developmental Biology
- Bone Metabolism
Background:
- Lead (Pb) exposure during development poses significant risks to skeletal health.
- Understanding the impact of Pb on bone metabolism across different developmental stages is crucial.
- Dimercaptosuccinic acid (DMSA) is a chelating agent used to treat heavy metal poisoning.
Purpose of the Study:
- To investigate the effects of Pb exposure and DMSA chelation therapy on bone metabolism in young rats at different ages.
- To elucidate the potential mechanisms underlying Pb-induced bone alterations and the efficacy of DMSA treatment.
Main Methods:
- Young rats were exposed to lead acetate during infanthood, childhood, and adolescenthood.
- Rats received one or two courses of DMSA chelation therapy.
- Measurements included blood/bone lead levels, calciotropic hormones, bone turnover markers (mRNA/protein), and bone microarchitecture (Micro-CT).
Main Results:
- Lead exposure during infanthood resulted in the most significant increases in blood/bone lead and detrimental changes in bone microstructures compared to other developmental stages.
- Pb exposure decreased bone formation markers (osteocalcin, RUNX2) and increased bone resorption markers (CTX), alongside altered parathormone (PTH) and vitamin D levels.
- DMSA chelation partially reversed Pb-induced bone damage, with the most significant improvements observed when therapy was initiated during infanthood.
Conclusions:
- Developmental lead exposure significantly impairs bone microstructures and metabolism, with infanthood being the most vulnerable period.
- DMSA chelation therapy offers partial reversal of lead's adverse effects on bone.
- The efficacy of DMSA chelation therapy for lead toxicity is age-dependent, with earlier intervention yielding better outcomes.
Objective:
To explore the impacts of Pb exposure and the dimercaptosuccinic acid (DMSA) chelation therapy on bone metabolisms in young rats of different ages, as well as the potential mechanisms.
Method:
Young rats were exposed to 0.05%-0.1% Pb acetate for 19 days, during infanthood (postnatal day, PND2-20), childhood (PND21-39) and adolescenthood (PND40-58) respectively. In each developmental stage, rats were further divided into three subgroups: lead-exposed, one-course and two-course DMSA chelation therapy subgroups. Blood/bone lead concentrations, serum calciotropic hormones concentrations, and mRNA and protein expressions of bone turnover markers in the serum and bones were measured. Bone microstructures were analyzed using Micro-CT.
Results:
Compared with lead-exposed during childhood and adolescenthood, increases in blood/bone lead levels, and the changes of blood/bone lead and trabecular bone microstructures after one-course DMSA chelation were most significant in rats lead-exposed during infanthood (P < .05). The serum osteocalcin (OC) concentrations, mRNA/protein expressions of OC and runt-related transcription factor 2 (RUNX2) in bones all decreased after Pb exposure, along with significant increases in serum C-terminal telopeptide of type I collagen (CTX) concentrations (P < .05). These effects were accompanied by changes of serum parathormone (PTH) and 1,25-dihydroxyvitamin D3 (1,25-(OH2)-D3) concentrations. DMSA chelation partially reversed the changes of bone microarchitectures, bone formation and resorption markers, and calciotropic-hormones, and the efficiency was greatest when the therapy was provided during infanthood.
Conclusion:
Developmental Pb exposure impaired bone microstructures and interfered bone metabolism, and the exposure effect was more obvious during infanthood than during childhood and adolescenthood. Lead effects were partially reversed by chelation therapy, and the efficacy may be most significant when the therapy was provided at younger ages.
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