Effect of Ascorbic Acid and Its Hydrophobic Derivative Palmitoyl Ascorbate on the Redox State of Primary Human Fibroblasts

Abstract

Ascorbic acid (AA) and its derivatives participate in vitro in oxidative-reductive reactions both as antioxidants and as prooxidants. The physiological relevance of these prooxidant effects of AA and its derivatives remains unclear. There is little evidence that AA can initiate formation of reactive oxygen species (ROS) or lipid peroxidation in cells or tissue. In order to examine the effect of AA and its derivative palmitoyl ascorbate on in situ intracellular ROS production and lipid peroxidation, 2('),7(')-dichlorofluorescin diacetate (DCFH-DA) and cis-parinaric acid were used as fluorescent probes in cultural neonatal foreskin fibroblasts. The results demonstrated that the effect of AA depended on the in vitro growth conditions. AA induced augmentation of the intracellular ROS concentration in newly plated (24 hours) cells. However, in cells cultured for 72 hours, AA had a different effect: it moderately reduced intracellular ROS concentration but stimulated lipid peroxidation in the cytoplasmic membrane. Palmitoyl ascorbate demonstrated significant inhibition of intracellular DCFH-DA oxidation presumably caused by inhibition of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase.

Further investigations on the role of ascorbic acid in stratum corneum lipid models after UV exposure

“…Ascorbic acid acts antioxidatively when added to the cell culture because of its redox cycling abilities. The results obtained in our HaCaT keratinocytes experiments are comparable with the results of Rosenblat et al (2001). The Rosenblat group used dermal and foreskin fibroblasts for studying ascorbic acid and palmitoyl ascorbate.…”

Palmitoyl Ascorbate Liposomes and Free Ascorbic Acid: Comparison of Anticancer Therapeutic Effects Upon Parenteral Administration

“…Reduction of anticancer toxicity of PAL by ROS inhibitors and metal chelators indicates a mechanism of action that resembles those described for free AA (4,23,24) and for PA (10,24). The mechanism through which extracellular ascorbate and intracellular iron exert this anticancer toxicity is unknown and is currently under investigation.…”

Surface Modification of Pharmaceutical Nanocarriers with Ascorbate Residues Improves their Tumor-Cell Association and Killing and the Cytotoxic Action of Encapsulated Paclitaxel In Vitro

“…For example, in vivo studies require intravenous as opposed to oral administration of ascorbate to produce elevated serum ascorbate concentrations in rodents (6) as well as in people (23). The results of in vitro studies can be influenced by cell culture conditions such as the nutrient profile of the cell culture media (24), cell density, the length of time since cell passage (15), and other factors. Even the genetic background of the mice can be critical, as was observed in ascorbate-deficient Gulo −/− mice (25,26).…”

“…As a result, several hydrophobized derivatives of ascorbate have been explored as stable alternatives (15,16). Such hydrophobized derivatives retain the antioxidant effects of ascorbate (15) and are more stable in biological milieu.…”

“…As a result, several hydrophobized derivatives of ascorbate have been explored as stable alternatives (15,16). Such hydrophobized derivatives retain the antioxidant effects of ascorbate (15) and are more stable in biological milieu. Moreover, hydrophobized derivatives of ascorbate offer the potential for the formulation of ascorbatebearing pharmaceutical nanocarriers (16,17).…”