Endocrine gland specific mechanistic paradigms of toxicity induced by metallic nanoparticles

Nanoparticles (NPs), due to their small size and unique physico-chemical properties are now being increasingly utilized in agriculture, commerce, industry and medicine, raising concerns about their systemic health effects on human health. Amongst vulnerable systems, the endocrine glands have been identified as critical target(s) of NP toxicity. Present review highlights current understanding of mechanisms viz. oxidative stress, inflammation, apoptosis disruption of hormone synthesis and metabolism, involved in endocrine toxicity of metallic nanoparticles. Experimental evidence suggests that NPs can enter endocrine glands, mimic hormones, interact with hormone receptors and disrupt downstream signaling pathways. Specific effects of NPs thus induced in endocrine glands viz. thyroid, parathyroid, thymus, pineal, pancreas, adrenals, placenta and hypothalamo-pituitary axis have been documented. Since, a few nanoparticles do exhibit antioxidant properties or therapeutic potential, their dual role as endocrine disruptors and therapeutic agents contributes to diverse and complex biological manifestations. The review emphasizes the need for advanced experimental models, including organ chip systems and multi-omic approaches to better evaluate NP-induced endocrine disruption. The review concludes that endocrine toxicity remains crucial for risk assessment and safe integration of nanotechnology into health care, theranostics, industrial, commercial and environmental applications.