Multifunctional Glycine-Carbon Dots Protect Against Arsenic Hepatotoxicity Through Redox Balance and PI3K/AKT Activation.

BACKGROUND

The theranostic potential of glycine-derived carbon dots (Gly/CDs) against arsenic-induced hepatotoxicity remains largely unexplored. This study aimed to synthesize Gly/CDs via a green, microwave-assisted method and to systematically evaluate their hepatoprotective efficacy and underlying mechanisms in a sodium arsenite (NaAsO2)-induced hepatic injury model.

METHODS

Gly/CDs were synthesized using citric acid, urea, and glycine as precursors. Their physicochemical properties were characterized using transmission electron microscopy (TEM), fluorescence spectroscopy, Fourier-transform infrared (FTIR) spectroscopy, and X-ray photoelectron spectroscopy (XPS). Following in vivo biocompatibility assessment, a murine model of NaAsO2-induced hepatotoxicity was established to evaluate therapeutic efficacy. Comprehensive biochemical assays, histopathological examinations, and transcriptomic analyses were conducted to assess oxidative stress, inflammatory responses, DNA damage, apoptosis, fibrosis, and the involved molecular pathways.

RESULTS

Gly/CDs exhibited excellent biocompatibility and demonstrated significant hepatoprotective effects, including restoration of redox homeostasis, suppression of pro-inflammatory cytokines, and attenuation of hepatocellular DNA damage, apoptosis, and fibrotic remodeling. Transcriptomic profiling suggested the involvement of the PI3K/AKT signaling pathway as a key molecular axis associated with the observed therapeutic effects. Overall, Gly/CDs preserved hepatic structure and function under chronic arsenic exposure.

CONCLUSION

This study provides the first comprehensive evidence that Gly/CDs function as biologically active nano-antioxidants capable of mitigating arsenic-induced hepatotoxicity through redox modulation and modulation of PI3K/AKT signaling activity. Given their low toxicity, ease of synthesis, and multifunctional properties, Gly/CDs represent a promising nanotherapeutic platform for applications in redox biology, toxicology, and environmental health.