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Myeloperoxidase (MPO) is a vital component of the innate immune system, which produces the potent oxidant hypochlorous acid (HOCl) to kill invading pathogens. However, an overproduction of HOCl during chronic inflammatory conditions causes damage to host cells, which promotes disease, including atherosclerosis. As such, there is increasing interest in the use of thiocyanate (SCN − ) therapeutically to decrease inflammatory disease, as SCN − is the favoured substrate for MPO, and a potent competitive inhibitor of HOCl formation. Use of SCN − by MPO forms hypothiocyanous acid (HOSCN), which can be less damaging to mammalian cells. In this study, we examined the ability of SCN − to modulate damage to macrophages induced by HOCl, which is relevant to lesion formation in atherosclerosis. Addition of SCN − prevented HOCl-mediated cell death, altered the extent and nature of thiol oxidation and the phosphorylation of mitogen activated protein kinases. These changes were dependent on the concentration of SCN − and were observed in some cases, at a sub-stoichiometric ratio of SCN − : HOCl. Co-treatment with SCN − also modulated HOCl-induced perturbations in the expression of various antioxidant and inflammatory genes. In general, the data reflect the conversion of HOCl to HOSCN, which can induce reversible modifications that are repairable by cells. However, our data also highlight the ability of HOSCN to increase pro-inflammatory gene expression and cytokine/chemokine release, which may be relevant to the use of SCN − therapeutically in atherosclerosis. Overall, this study provides further insight into the cellular pathways by which SCN − could exert protective effects on supplementation to decrease the development of chronic inflammatory diseases, such as atherosclerosis.

Palmitoyl ascorbate (PA) as an antioxidant has the potential for the treatment of cancer. In the present study, a nanocarrier system was developed for co-delivery of docetaxel (DOC) with palmitoyl ascorbate and the therapeutic efficacy of a combination drug regimen was investigated. For this purpose, different ratios of docetaxel and palmitoyl ascorbate were co-encapsulated in a liposome and they all showed high encapsulation efficiency. The average diameters of the liposomes ranged from 140 to 170 nm. Negative zeta potential values were observed for all systems, ranged from −40 mV to −56 mV. Studies on drug release and cellular uptake of the co-delivery system demonstrated that both drugs were effectively taken up by the cells and released slowly. Moreover, the liposome loading drugs with DOC/PA concentration ratio of 1:200 showed the highest anti-tumor activity to three different types of tumor cells. The higher in vivo therapeutic efficacy with lower systemic toxicity of the DOC-PA200-LPs was also verified by the H22 tumor bearing mice model. Our results showed that such co-loaded delivery systems could serve as a promising therapeutic approach to improve clinical outcomes against hepatic carcinoma.

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