ascorbic-acid and perfluorooctane-sulfonic-acid

Perfluorooctanesulfonate (PFOS) is a persistent pollutant that can induce toxic effects, including leukemia, on blood cells. Vitamin C (VC), a functional nutrient, has been found to possess potent cytoprotective effects. However, there are currently no reports on its ability to treat PFOS-associated leukemia. This study used a molecular networking analysis to reveal the functional action and pharmacological mechanism of VC against PFOS-associated leukemia. The biological informatics findings revealed a total of 17 intersection targets against PFOS-associated leukemia. In addition, seven core-functional targets, including tumor protein p53 (TP53), mitogen-activated protein kinase 1 (MAPK1), estrogen receptor 1 (ESR1), sirtuin 1 (SIRT1), nitric oxide synthase 3 (NOS3), myeloid cell leukemia-1 (MCL1), and telomerase reverse transcriptase (TERT), were screened and identified. Notably, the molecular docking findings indicated that TP53, MAPK1, and ESR1 were potent pharmacological targets of VC against PFOS-associated leukemia. Moreover, the pharmacological functions including biological processes, cell components, and molecular pathways of VC against PFOS-associated leukemia were determined. According to the computational findings, we conclude that VC protects against PFOS-associated leukemia action by suppressing leukemia-associated cell proliferation and tumor growth. The validated genes of TP53, MAPK1, ESR1 may become potential biomarkers for monitoring and treating PFOS-associated leukemia.

Topics: Alkanesulfonic Acids; Ascorbic Acid; Fluorocarbons; Humans; Leukemia; Molecular Docking Simulation; Signal Transduction

Our previous studies show that vitamin C (VC) plays promising hepatoprotection in mice. Intrahepatic exposure of perfluorooctane sulfonate (PFOS) can induce dose-dependent cytotoxicity. However, pharmacology-based assessment of VC on PFOS remains uninvestigated. This study aimed to evaluate the therapeutic benefits of VC on inhibiting PFOS-induced liver steatosis in mice, followed by representative biochemical analysis and immunoassay. As results, VC was beneficial for reduced PFOS-induced liver damages, as showed in reductions of serological levels of transaminases (ALT and AST), lipids (TG and TC), fasting glucose and insulin, inflammatory cytokines (TNF-α and IL6), while content of fibroblast growth factor 21 (FGF21) in serum was increased. In addition, VC reduced histiocytic changes of PFOS-lesioned livers, as revealed in reduced TNF-α-labeled cells and increased FGF21-labeled cells in immunofluorescence assay. Further, intrahepatic expressions of endoplasmic reticulum (ER) stress-based ATF6, eIF2α, GRP78, XBP1 proteins were down-regulated by treatments of VC. Taken together, our preliminary findings set forth that VC exerts pharmacological benefits against PFOS-induced liver steatosis in mice, and the underlying biological mechanism may be linked to suppressing hepatocellular inflammatory reaction and ER stress.

Topics: Alkanesulfonic Acids; Animals; Anti-Inflammatory Agents; Ascorbic Acid; Chemical and Drug Induced Liver Injury; Endoplasmic Reticulum Chaperone BiP; Endoplasmic Reticulum Stress; Fluorocarbons; Male; Mice, Inbred ICR; Protective Agents; Vitamins