Vitamin C prevents nickel accumulation in rat brain through affecting its transport via serum albumin

Abstract

Nickel (Ni²⁺) exposure has been linked to oxidative stress, reproductive toxicity, and neurotoxicity. Human serum albumin (HSA), a major plasma transport protein, that plays a critical role in the systemic distribution of xenobiotics, including heavy metals. This study aimed to investigate how vitamin C affects the interaction between Ni²⁺ and HSA, and whether this interaction influences nickel accumulation in the brain.

Male rats were divided into three groups: a control group receiving vitamin C alone, a group exposed to nickel, and a group receiving both nickel and vitamin C. Atomic absorption spectroscopy revealed that co-treatment with vitamin C significantly reduced nickel accumulation in brain tissue compared to nickel exposure alone. To elucidate the underlying mechanism, in vitro and in silico approaches were employed. Spectroscopic analyses—including fluorescence quenching, site marker displacement, synchronous fluorescence, and circular dichroism (CD)—revealed that vitamin C competitively interferes with Ni²⁺ binding to HSA and protects the native structure of the protein from nickel-induced conformational changes. Notably, the binding affinity of Ni²⁺ to HSA was lower in the presence of vitamin C. Molecular dynamics simulations supported these findings, indicating structural destabilization of the Ni–HSA complex when vitamin C was present. Together, these results suggest that vitamin C modulates Ni²⁺ transport by altering its binding to HSA, which may partly explain its protective effect against nickel-induced neurotoxicity. Further research is needed to fully elucidate transport mechanisms of nickel across the blood–brain barrier.