Post-pubertal Susceptibility to Cadmium-Induced Cardiac Injury: Role of Metallothionein, Antioxidant Defense, and...

Cadmium (Cd), a widespread environmental contaminant, induces cardiotoxicity even at low doses through endocrine disruption and oxidative stress. This investigation assessed age-related susceptibility in female albino rats by comparing pre-pubertal (30-day-old) and post-pubertal (60-day-old) animals that were administered CdCl₂ at a dosage of 5.12 mg/kg body weight per day via oral gavage for 15 days. Despite greater Cd accumulation in pre-pubertal rats, post-pubertal animals exhibited heightened cardiac injury. This paradox correlated with impaired induction of metallothionein (MT), enhanced glutathione and vitamin C depletion, and reduced enzymic antioxidants (SOD, CAT, GPx). Concomitantly, altered adrenal function with increased corticosterone (CORT) and reduced estradiol (E2) reflected differential hypothalamic-pituitary-adrenal (HPA) axis responsiveness, further compromising antioxidant defenses. Biomarkers of cardiac function confirmed this vulnerability: increased serum CK-MB and troponin I, electrocardiographic (ECG) abnormalities (ST elevation, QT prolongation, tachycardia), and larger infarct volume. Collectively, these findings demonstrate that post-pubertal susceptibility is driven by reduced MT inducibility and HPA axis-mediated endocrine dysregulation, which amplify oxidative injury and structural remodeling of ventricular myocardium. From a translational standpoint, our findings identify adolescence and early adulthood as critical windows during which females exhibit heightened vulnerability to environmental CdCl₂ exposure. Variations in metallothionein (MT) expression capacity and estradiol levels may serve as informative biomarkers for predicting individual susceptibility. These results also suggest the potential value of targeted interventions such as MT induction, antioxidant therapy, or modulation of hormonal pathways, that merit further investigation. Collectively, the study emphasizes the urgent need for stricter regulation of cadmium exposure, particularly among peripubertal populations, to reduce lifelong cardiovascular risk.