Impact of gold nanoparticle exposure on the development pancreas and kidney: Dose-dependent;oxidative stress; miRNA expression and Nrf2/ARE Signalling

Abstract

Background: The widespread use of gold nanoparticles (AuNPs) in consumer and medical products necessitates investigation into their potential developmental toxicity. Aim of the work: This study investigated the systemic effects of in-utero AuNP exposure on developing male rat offspring, focusing on metabolic, organ-specific, and cellular pathways. Materials and methods: Pregnant rats were intravenously administered AuNPs (5, 10, 15, or 20 mg/kg) or saline from gestational day 1 to birth. Male offspring were assessed at postnatal day 60 through biochemical and genetic analyses in the pancreas, kidney tissues, plasma analysis, and pancreatic histology.

Results: No mortality or clinical abnormalities occurred. However, in-utero AuNP high-dose exposure induced pancreatic abnormalities, including reduced endocrine function and morphological damage. Higher doses disrupt body and organ growth, leading to metabolic dysregulation (elevated glucose, amylase, lipase, reduced insulin), impairing glucose homeostasis, and pancreatic dysfunction. Compromised kidney function (elevated urea, creatinine, BUN, electrolyte imbalances), increased oxidative stress, and dysregulated inflammatory responses (altered TNF-α, IL-6, IL-10, Nrf2, NF-κB) were also observed. AuNPs induced apoptosis (increased caspase-3, decreased Bcl-2, and altered COX-2), as well as dysregulation of mRNA and miRNA expression. Affected genes included those related to stress and inflammation (p-p38, NOX4, iNOS, NF-κB, Akt, mTOR, Anxa3) and cellular survival signalling (miR-21, miR-382, miR-34a, miR-223). Pancreatic histopathology revealed dose-dependent tissue damage. Conclusion: These results indicate that AuNPs, especially at higher doses, disrupt multiple biological processes, inducing metabolic, renal, and pancreatic dysfunction via oxidative stress, inflammation, and cellular dysregulation. Further mechanistic research is crucial to establish safe applications, highlighting the need for biosafety assessments guided by green toxicology principles.