Carbonyl stress caused by the accumulation of advanced glycation end products (AGEs) and excessive methylglyoxal production may be involved in the development of various neurodegenerative diseases. Sulfite is an endogenous intermediate of sulfur metabolism that protects against oxidative stress in neurons; however, the effect of sulfite on carbonyl stress in neuronal cells remains unclear.In this study, we examined the effects of sulfite on MGO-induced toxicity in human neuroblastoma SH-SY5Y cells. Pretreatment with sulfite attenuated MGO-induced cell death and suppressed the accumulation of MG-H1, which is a major MGO-derived AGE. These effects were accompanied by increased intracellular cysteine and glutathione levels and were abolished under cysteine/cystine-depleted conditions, which indicates that the enhancement of intracellular glutathione availability is the major intracellular mechanism underlying sulfite-mediated protection.In contrast, simultaneous treatment with sulfite suppressed MG-H1 formation, even in the absence of extracellular cysteine/cystine in SH-SY5Y cells. LC–MS/MS analysis revealed direct adduct formation between sulfite and MGO.These results indicate that sulfite modulates MGO-induced toxic responses in an in vitro neuronal cell model through glutathione-associated defense and direct extracellular sequestration of MGO.
Dracocephalum moldavica L. seed oil (DMS), obtained by supercritical CO2 extraction, has a chemical fingerprint dominated by unsaturated fatty acids and phytosterols, supporting its anti-inflammatory and skin-protective relevance. This study evaluated the topical safety profile and functional plausibility of DMS as a dermocosmetic ingredient using a non-animal testing framework. Phototoxicity was assessed using the 3T3 NRU phototoxicity assay (OECD TG 432), and skin irritation was evaluated in a reconstructed human epidermis (RHE) model. Regenerative potential was examined using a keratinocyte scratch assay and a RHE-based wound model to assess re-epithelialization responses. In parallel, a network-based in silico analysis was performed to explore biological plausibility by linking DMS-associated compounds to relevant biological processes and pathways in skin. Under the tested conditions, DMS was classified as non-phototoxic and non-irritant. DMS also enhanced wound closure in the scratch assay and promoted re-epithelialization in the 3D RHE wound model with regenerative efficacy peaking at an optimal concentration and declining at higher doses. Network analysis pointed to candidate processes involved in inflammation, cellular stress, and tissue repair that are consistent with the in vitro findings. Collectively, these results indicate that DMS is non-phototoxic and non-irritant under the tested conditions and shows concentration-dependent regenerative potential relevant to cosmetic ingredient development.
Priority environmental toxicant arsenic directly enters to the bloodstream through contaminated water or foodstuffs. Erythrocytes, being the most abundant and vulnerable blood cell therefore demand detailed assessment of the hazardous metalloid-driven impacts. This study investigates a mechanistic basis of arsenic-induced impairments in goat erythrocytes and further evaluates protective efficacy of melatonin against the alterations. In-vitro exposure of erythrocytes to 100 μM arsenic causes ROS accumulation and redox imbalance resulting morphological deformation and critical membrane proteins loss. Degradation of GLUT1, reduced intracellular glucose availability, binding affinity toward glucose, suppressed metabolic enzyme activities and uncompetitive inhibition induced destabilization of hexokinase secondary structure by arsenic collectively underlines a mechanism of the toxic metalloid-driven erythrocyte dysfunctions and energetic failure. However, co-incubation of erythrocytes with 100 μM melatonin significantly ameliorates the oxidative imbalances and preserves RBC morphology through its antioxidant and radical-scavenging efficacy. Melatonin preventing GLUT1 degradation and preserving hexokinase conformation supports erythrocyte bioenergetics as evidenced by enhanced metabolic enzyme activities and intracellular ATP levels. Alongside, direct binding of melatonin with arsenic through its chelation capability highlight the indolamine as a promising candidate to mitigate arsenic-induced cytotoxicity either through its pharmacological administration or through the inclusion of melatonin-rich foods in daily diet to benefit humankind.
Silica nanoparticles (SiO₂NPs) are increasingly used in biomedical and industrial applications, yet their effects on endothelial cell metabolism at the pathway level remain incompletely characterized. Here, we used 1H NMR-based metabolomics to investigate the metabolic response of human endothelial cells (HUV-EC-C) exposed to prolate SiO₂NP@biomolecule agglomerates formed spontaneously in serum-containing medium across a range of concentrations and incubation times. Exposure induced dose- and time-dependent metabolic reprogramming, characterized by increased glucose consumption and a metabolic profile consistent with increased glycolytic reliance, together with extracellular accumulation of succinate and glycolytic end-products consistent with alterations in TCA cycle-associated metabolism. Depletion of NADP+ and glutathione precursors, together with increased extracellular pyroglutamate, indicated alterations in redox-related metabolism and glutathione turnover, which were further supported by changes in intracellular reactive oxygen species levels. Additionally, reductions in phosphocholine-related metabolites and UDP-GlcNAc indicated alterations in phospholipid metabolism and protein glycosylation, while creatine-phosphocreatine depletion was consistent with impaired energy homeostasis. These metabolic alterations were accompanied by fluorescence microscopy evidence of cytoskeletal disorganization, cell shrinkage, and apoptotic-like features. Collectively, our findings identify dose- and time-dependent metabolic reprogramming in endothelial cells exposed to SiO₂NP@biomolecule agglomerates and support a working model involving alterations in glycolytic reliance, mitochondrial-associated metabolism, redox regulation, energy homeostasis, and membrane remodeling. Given that these mechanistic interpretations are primarily based on metabolomic profiles and complementary ROS measurements, further functional studies are required to establish the underlying metabolic pathways. These findings provide a metabolic framework for understanding endothelial responses to biologically transformed SiO₂NPs and their potential relevance to nanoparticle-induced vascular dysfunction.
