ascorbic-acid and alpha-tocopherol-phosphate

Topics: Acne Vulgaris; Adult; alpha-Tocopherol; Ascorbic Acid; Cicatrix; Cosmeceuticals; Drug Combinations; Erythema; Female; Glyceryl Ethers; Humans; Hyperpigmentation; Male; Skin Cream; Treatment Outcome; Young Adult

The standard management of acne vulgaris in Japan includes a combination of topical treatment with benzoyl peroxide (BPO) and BPO/clindamycin (CLDM), topical adapalene and systemic antimicrobials. However, the treatment of therapy-resistant complications such as postinflammatory hyperpigmentation (PIH), erosions with inflamed red papules and atrophic scars has not been established. We performed chemical peeling with glycolic acid and iontophoresis with ascorbyl 2-phosphate 6-palmitate and DL-α-tocopherol phosphate for the treatment of PIH, erosions with inflamed red papules and non-inflamed atrophic scars in 31 patients with acne vulgaris (mild to severe severity), and evaluated the efficacy and safety of these interventions. In most of cases, there was remarkable improvement in PIH and erosions with inflamed red papules after treatment. There was also some improvement in non-inflamed atrophic scars without erythema. Mild redness and irritation was observed in four cases as adverse reactions. Early initial treatment of PIH and erosions with red papules by chemical peeling and iontophoresis is an effective and safe method to prevent the formation of atrophic scars in patients with acne vulgaris.

Topics: Acne Vulgaris; Adapalene; Adolescent; Adult; alpha-Tocopherol; Anti-Infective Agents; Ascorbic Acid; Atrophy; Benzoyl Peroxide; Chemexfoliation; Cicatrix; Clindamycin; Combined Modality Therapy; Erythema; Female; Glycolates; Humans; Hyperpigmentation; Iontophoresis; Japan; Male; Severity of Illness Index; Treatment Outcome; Young Adult

The CD36 scavenger receptor binds several ligands and mediates ligand uptake and ligand-dependent signal transduction and gene expression, events that may involve CD36 internalization. Here we show that CD36 internalization in THP-1 monocytes is triggered by α-tocopherol (αT) and more strongly by α-tocopheryl phosphate (αTP) and EPC-K1, a phosphate diester of αTP and L-ascorbic acid. αTP-triggered CD36 internalization is prevented by the specific covalent inhibitor of selective lipid transport by CD36, sulfo-N-succinimidyl oleate (SSO). Moreover, SSO inhibited the CD36-mediated uptake of 14C-labelled αTP suggesting that αTP binding and internalization of CD36 is involved in cellular αTP uptake, whereas the uptake of αT was less affected. Similar to that, inhibition of selective lipid transport of the SR-BI scavenger receptor resulted mainly in reduction of αTP and not αT uptake. In contrast, uptake of αT was mainly inhibited by Dynasore, an inhibitor of clathrin-mediated endocytosis, suggesting that the differential regulatory effects of αTP and αT on signaling may be influenced by their different routes of uptake. Interestingly, αTP and EPC-K1 also reduced the neutral lipid content of THP-1 cells and the phagocytosis of fluorescent Staphylococcus aureus bioparticles. Moreover, induction of the vascular endothelial growth factor (VEGF) promoter activity by αTP occurred via CD36/PI3Kγ/Akt, as it could be inhibited by specific inhibitors of this pathway (SSO, Wortmannin, AS-605240). These results suggest that αTP activates PI3Kγ/Akt signaling leading to VEGF expression in monocytes after binding to and/or transport by CD36, a receptor known to modulate angiogenesis in response to amyloid beta, oxLDL, and thrombospondin. J. Cell. Biochem. 118: 1855-1867, 2017. © 2017 Wiley Periodicals, Inc.

Topics: alpha-Tocopherol; Ascorbic Acid; CD36 Antigens; Cell Line, Tumor; Class Ib Phosphatidylinositol 3-Kinase; HEK293 Cells; Humans; Macrophages; Monocytes; Phagocytosis; Signal Transduction; Staphylococcus aureus; THP-1 Cells; Vascular Endothelial Growth Factor A; Vitamin E

A previous study showed that high doses of methamphetamine induce self-injurious behavior (SIB) in rodents. Furthermore, the combination of methamphetamine and morphine increased lethality in mice. We recently surmised that the rise in SIB and mortality induced by methamphetamine and/or morphine may be related to oxidative stress. The present study was designed to determine whether an antioxidant could inhibit SIB or mortality directly induced by methamphetamine and/or morphine. The SIB induced by 20mg/kg of methamphetamine was abolished by the administration of Na L-ascorbyl-2-phosphate (APS: 300 mg/kg), but not Na DL-alpha-tocopheryl phosphate (TPNa: 200mg/kg). In contrast, APS (300 mg/kg) and TPNa (200mg/kg) each significantly attenuated the lethality induced by methamphetamine and morphine. The present study showed that the signal intensity of superoxide adduct was increased by 20mg/kg of methamphetamine in the heart and lungs, and methamphetamine plus morphine tended to increase superoxide adduct in all of the tissues measured by ESR spin trap methods. Adduct signal induced in brain by methamphetamine administration increased in significance, but in mouse administrated methamphetamine plus morphine. There are differential effects of administration of methamphetamine and coadministration of methamphetamine plus morphine on adduct signal. These results suggest that APS and TPNa are effective for reducing methamphetamine-induced toxicity and/or toxicological behavior. While APS and TPNa each affected methamphetamine- and/or morphine-induced toxicology and/or toxicological behavior, indicating that both drugs have antioxidative effects, their effects differed.

Topics: alpha-Tocopherol; Animals; Antioxidants; Ascorbic Acid; Central Nervous System Stimulants; Dopamine; Electron Spin Resonance Spectroscopy; Free Radicals; Iron-Binding Proteins; Male; Methamphetamine; Mice; Mice, Inbred BALB C; Molecular Structure; Morphine; Neurotoxicity Syndromes; Self-Injurious Behavior

Chronic morphine-induced withdrawal syndrome after morphine cessation remains a severe obstacle in the clinical treatment of morphine. Previous studies have shown that nitric oxide synthetase (NOS) inhibitors may have therapeutic potential in morphine withdrawal in humans. The mechanisms that underlie expression of morphine-induced withdrawal syndrome are, however, not yet fully understood. Therefore, this study was designed to determine the mechanism of the expression of morphine-induced withdrawal syndrome in mice. Morphine-dependent mice showed marked body weight loss and several withdrawal signs after naloxone challenge. Pretreatment with a NOS inhibitor, such as N-nitro-L-arginine methyl ester (L-NAME) or 7-nitroindazole, but not aminoguanidine, significantly attenuated the expression of morphine-induced withdrawal syndrome. Furthermore, mepacrine (a phospholipase A2 inhibitor) significantly attenuated the morphine-induced withdrawal syndrome in a manner that was different than that with a NOS inhibitor. These results suggest that nNOS and phospholipase A2, which might increase free radicals, play an important role in the expression of morphine-induced withdrawal syndrome. On the contrary, free radical scavengers (including fullerenes, ascorbate-2-phosphate, and DL-alpha-tocopheryl phosphate) attenuated the expression of the morphine-induced withdrawal syndrome. These results indicate that free radicals play an important role in the expression of physical dependence on morphine, and fullerenes could be a potential clinical tool in the relief of morphine withdrawal syndrome.

Topics: alpha-Tocopherol; Animals; Ascorbic Acid; Enzyme Inhibitors; Free Radical Scavengers; Hydroxyl Radical; Male; Mice; Naloxone; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Opioid-Related Disorders; Phospholipase A2 Inhibitors; Substance Withdrawal Syndrome; Superoxides

The goal of the current study was to evaluate the effects of arachidonic acid, as a representative polyunsaturated fatty acid, on the viability of a Hep G2 cell line, which has been transduced to express human cytochrome P4502E1 (CYP2E1). Arachidonic acid produced a concentration- and time-dependent toxicity to Hep G2-MV2E1-9 cells, which express CYP2E1, but little or no toxicity was found with control Hep G2-MV-5 cells, which were infected with retrovirus lacking human CYP2E1 cDNA. In contrast to arachidonic acid, oleic acid was not toxic to the Hep G2-MV2E1-9 cells. The cytotoxicity of arachidonic acid appeared to involve a lipid peroxidation type of mechanism since toxicity was enhanced after depletion of cellular glutathione; formation of malondialdehyde and 4-hydroxy-2-nonenal was markedly elevated in the cells expressing CYP2E1, and toxicity was prevented by antioxidants such as alpha-tocopherol phosphate, 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (trolox), propylgallate, ascorbate, and diphenylphenylenediamine, and the iron chelator desferrioxamine. Transfection of the Hep G2-MV2E1-9 cells with plasmid containing CYP2E1 in the sense orientation enhanced the arachidonic acid toxicity, whereas transfection with plasmid containing CYP2E1 in the antisense orientation decreased toxicity. The CYP2E1-dependent arachidonic acid toxicity appeared to involve apoptosis, as demonstrated by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling and DNA laddering experiments. Trolox, which prevented toxicity of arachidonic acid, also prevented the apoptosis. Transfection with a plasmid containing bcl-2 resulted in complete protection against the CYP2E1-dependent arachidonic acid toxicity. It is proposed that elevated production of reactive oxygen intermediates by cells expressing CYP2E1 can cause lipid peroxidation, which subsequently promotes apoptosis and cell toxicity when the cells are enriched with polyunsaturated fatty acids such as arachidonic acid. The Hep G2-MV2E1-9 cells appear to be a valuable model to study interaction between CYP2E1, polyunsaturated fatty acids, reactive radicals, and the consequence of these interactions on cell viability and to reproduce several of the key features associated with ethanol hepatotoxicity in the intragastric infusion model of ethanol treatment.

Topics: alpha-Tocopherol; Antioxidants; Apoptosis; Ascorbic Acid; Aspirin; Carcinoma, Hepatocellular; Cell Survival; Chromans; Cytochrome P-450 CYP2E1; Deferoxamine; Humans; L-Lactate Dehydrogenase; Liver Neoplasms; Oleic Acid; Phenylenediamines; Propyl Gallate; Proto-Oncogene Proteins c-bcl-2; Recombinant Proteins; Transfection; Tumor Cells, Cultured; Vitamin E