Benefits of Combinations of Vitamin A, C and E Derivatives in the Stability of Cosmetic Formulations

Chemically stable ester derivatives of vitamins A, C and E have become a focus of interest for their role in the satisfactory results in skin aging treatments. Accordingly, the aim of this study was to evaluate the physical and chemical stability of a cosmetic formulation containing 1% retinyl palmitate, ascorbyl tetraisopalmitate and tocopheryl acetate, alone or in combination. In the studies of physical stability, a Brookfield rheometer was used to determine rheological behavior of formulations containing the vitamins. Chemical stability was determined by HPLC on a Shimadzu system with UV detection. Results showed that formulations had pseudoplastic behavior and that vitamins did not alter their apparent viscosity and thixotropy. In the chemical stability studies, first-order reaction equations were used for determinations of the shelf-life of vitamins derivatives considering a remaining concentration of 85%. Combined vitamins in a single formulation had a slightly lower degradation rate as compared to different preparations containing only one of the vitamins. Considering that many cosmetic formulations contain vitamin combinations it is suggested that the present study may contribute to the development of more stable formulations containing liposoluble vitamins.

The antioxidative effect of de novo generated vitamin B-6 in Plasmodium falciparum validated by protein interference

The malaria parasite Plasmodium falciparum is able to synthesize de novo PLP (pyridoxal 5'-phosphate), the active form of vitamin B-6. In the present study, we have shown that the de novo synthesized PLP is used by the parasite to detoxify O-1(2) (singlet molecular oxygen), a highly destructive reactive oxygen species arising from haemoglobin digestion. The formation of O-1(2) and the response of the parasite were monitored by live-cell fluorescence microscopy, by transcription analysis and by determination of PLP levels in the parasite. Pull-down experiments of transgenic parasites overexpressing the vitamin B-6-biosynthetic enzymes PfPdx1 and PfPdx2 clearly demonstrated an interaction of the two proteins in vivo which results in an elevated PLP level from 12.5 mu M in wild-type parasites to 36.6 mu M in the PfPdx1/PfPdx2-overexpressing cells and thus to a higher tolerance towards O-1(2). In contrast, by applying the dominant-negative effect on the cellular level using inactive mutants of PfPdx1 and PfPdx2, P. falciparum becomes susceptible to O-1(2). Our results demonstrate clearly the crucial role of vitamin B-6 biosynthesis in the detoxification of O-1(2) in P falciparum. Besides the known role of PLP as a cofactor of many essential enzymes, this second important task of the vitamin B-6 de novo synthesis as antioxidant emphasizes the high potential of this pathway as a target of new anti-malarial drugs.

Vitamin D receptor polymorphisms in hypertensive disorders of pregnancy

Hypertension is the most common medical disorder in pregnancy, and a leading cause of maternal and neonatal morbidity and mortality. Vitamin D endocrine system has important influence on immune modulation and endothelial function, which play a role in preeclampsia (PE) and gestational hypertension (GH). Vitamin D receptor (VDR) is present in a large variety of cell types, including placental cells. We examined whether there is an association between VDR polymorphisms (FokI, ApaI and BsmI) with PE or with GH. Restriction fragment length polymorphism techniques were used to genotype 529 pregnant (154 with GH, 162 with PE, and 213 healthy pregnant-HP). VDR haplotype frequencies were inferred using the PHASE 2.1 program. We found similar genotype distributions for the three VDR polymorphisms in both PE and GH groups compared with the HP group (all P > 0.05). In parallel with these findings, the VDR haplotype frequency distribution was similar in both PE and GH groups compared with the HP group (all P > 0.05). Our results showing no significant association between VDR polymorphisms or haplotypes with PE or GH suggest that genetic variations in VDR do not predispose to hypertensive disorders of pregnancy.

Influence of Roux-en-Y Gastric Bypass Surgery on Vitamin C, Myeloperoxidase, and Oral Clinical Manifestations: A 2-Year Follow-Up Study

Background: Bariatric surgery influences the intake and absorption of nutrients. The serum concentrations of vitamin C, myeloperoxidase (MPO) and oral clinical manifestations were examined in patients two years after Roux-en-Y gastric bypass (RYGB). Methods: Clinical prospective-study with control-group (CG; n = 26), assessed only once, and the bariatric-group (BG; n = 26), assessed in the basal period and at 12 and 24 months after surgery. The mean ages in the CG and BG were 37.8 +/- 1.51 and 39.6 +/- 1.93 years, respectively, and their body mass indices were 22.07 +/- 0.29 and 45.62 +/- 1.46 kg/m2, respectively. Results: At 12 months after surgery, increased episodes of vomiting (P < .001) and dental hypersensitivity (P=.012) were observed, with a reduction in the saliva buffering capacity of 21.3 2.9% (P=.004). At 24 months after RYGB, we detected a significant reduction in serum vitamin C (32.9 +/- 5.3%, P < .001) and MPO values were higher than in the basal period (P = .032). With regard to oral hygiene habits, 92.3% of patients reported frequent tooth brushing and 96.1% used fluoride, which were similar across the two years. However, dental hypersensitivity (P = .048) was significantly increased than baseline. Conclusions: The results demonstrated that vitamin C deficiency and increased vomiting after RYGB for morbid obesity may contribute to increased periodontal disease. The fact it is impossible to determine which factors (diet, poor compliance with supplementation, vomiting, poor oral hygiene) contributed to the dental problems in these patients is a shortcoming of the report. (Nutr Clin Pract. 2012; 27: 114-121)

Kinin-B2 Receptor Mediated Neuroprotection after NMDA Excitotoxicity Is Reversed in the Presence of Kinin-B1 Receptor Agonists

Background: Kinins, with bradykinin and des-Arg(9)-bradykinin being the most important ones, are pro-inflammatory peptides released after tissue injury including stroke. Although the actions of bradykinin are in general well characterized; it remains controversial whether the effects of bradykinin are beneficial or not. Kinin-B2 receptor activation participates in various physiological processes including hypotension, neurotransmission and neuronal differentiation. The bradykinin metabolite des-Arg(9)-bradykinin as well as Lys-des-Arg(9)-bradykinin activates the kinin-B1 receptor known to be expressed under inflammatory conditions. We have investigated the effects of kinin-B1 and B2 receptor activation on N-methyl-Daspartate (NMDA)-induced excitotoxicity measured as decreased capacity to produce synaptically evoked population spikes in the CA1 area of rat hippocampal slices. Principal Findings: Bradykinin at 10 nM and 1 mu M concentrations triggered a neuroprotective cascade via kinin-B2 receptor activation which conferred protection against NMDA-induced excitotoxicity. Recovery of population spikes induced by 10 nM bradykinin was completely abolished when the peptide was co-applied with the selective kinin-B2 receptor antagonist HOE-140. Kinin-B2 receptor activation promoted survival of hippocampal neurons via phosphatidylinositol 3-kinase, while MEK/MAPK signaling was not involved in protection against NMDA-evoked excitotoxic effects. However, 100 nM Lys-des-Arg(9)-bradykinin, a potent kinin-B1 receptor agonist, reversed bradykinin-induced population spike recovery. The inhibition of population spikes recovery was reversed by PD98059,showing that MEK/MAPK was involved in the induction of apoptosis mediated by the B1 receptor. Conclusions: Bradykinin exerted protection against NMDA-induced excitotoxicity which is reversed in the presence of a kinin-B1 receptor agonist. As bradykinin is converted to the kinin-B1 receptor metabolite des-Arg(9)-bradykinin by carboxypeptidases, present in different areas including in brain, our results provide a mechanism for the neuroprotective effect in vitro despite of the deleterious effect observed in vivo.

Enhancement of blood-tumor barrier permeability by Sar-[D-Phe8]des-Arg9BK, a metabolically resistant bradykinin B1 agonist, in a rat C6 glioma model

Abstract Background While it is well known that bradykinin B2 agonists increase plasma protein extravasation (PPE) in brain tumors, the bradykinin B1 agonists tested thus far are unable to produce this effect. Here we examine the effect of the selective B1 agonist bradykinin (BK) Sar-[D-Phe8]des-Arg9BK (SAR), a compound resistant to enzymatic degradation with prolonged activity on PPE in the blood circulation in the C6 rat glioma model. Results SAR administration significantly enhanced PPE in C6 rat brain glioma compared to saline or BK (p < 0.01). Pre-administration of the bradykinin B1 antagonist [Leu8]-des-Arg (100 nmol/Kg) blocked the SAR-induced PPE in the tumor area. Conclusions Our data suggest that the B1 receptor modulates PPE in the blood tumor barrier of C6 glioma. A possible role for the use of SAR in the chemotherapy of gliomas deserves further study.

Relationship between Vitamin D Receptor gene polymorphisms and the components of metabolic syndrome

Abstract Background The Vitamin D Receptor gene (VDR) is expressed in many tissues and modulates the expression of several other genes. The purpose of this study was to investigate the association between metabolic syndrome (MetSyn) with the presence of VDR 2228570 C > T and VDR 1544410 A > G polymorphisms in Brazilian adults. Methods Two hundred forty three (243) individuals were included in a cross-sectional study. MetSyn was classified using the criteria proposed by National Cholesterol Educational Program - Adult Treatment Panel III. Insulin resistance and β cell secretion were estimated by the mathematical models of HOMA IR and β, respectively. The VDR 2228570 C > T and VDR 1544410 A > G polymorphisms were detected by enzymatic digestion and confirmed by allele specific PCR or amplification of refractory mutation. Results Individuals with MetSyn and heterozygosis for VDR 2228570 C > T have higher concentrations of iPTH and HOMA β than those without this polymorphism, and subjects with recessive homozygosis for the same polymorphisms presented higher insulin resistance than those with the heterozygous genotype. There is no association among VDR 1544410 A > G and components of MetSyn, HOMA IR and β, serum vitamin D (25(OH)D3) and intact parathormone (iPTH) levels in patients with MetSyn. A significant lower concentration of 25(OH)D3 was observed only in individuals without MetSyn in the VDR 1544410 A > G genotype. Additionally, individuals without MetSyn and heterozygosis for VDR 2228570 C > T presented higher concentration of triglycerides and lower HDL than those without this polymorphism. Conclusions Using two common VDR polymorphism data suggests they may influence insulin secretion, insulin resistance an serum HDL-cholesterol in our highly heterogeneous population. Whether VDR polymorphism may influence the severity of MetSyn component disorder, warrants examination in larger cohorts used for genome-wide association studies.

Vitamin C and Vitamin E in Prevention of Nonalcoholic Fatty Liver Disease (NAFLD) in Choline Deficient Diet Fed Rats

Abstract Aim Oxidative stress has been implicated in the pathogenesis of Nonalcoholic Fatty Liver Disease (NAFLD). Vitamin C and vitamin E are known to react with reactive oxygen species (ROS) blocking the propagation of radical reactions in a wide range of oxidative stress situations. The potential therapeutic efficacy of antioxidants in NAFLD is unknown. The aim of this study was to evaluate the role of antioxidant drugs (vitamin C or vitamin E) in its prevention. Methods Fatty liver disease was induced in Wistar rats by choline-deficient diet for four weeks. The rats were randomly assigned to receive vitamin E (n = 6) – (200 mg/day), vitamin C (n = 6) (30 mg/Kg/day) or vehicle orally. Results In the vehicle and vitamin E-treated rats, there were moderate macro and microvesicular fatty changes in periportal area without inflammatory infiltrate or fibrosis. Scharlach stain that used for a more precise identification of fatty change was strong positive. With vitamin C, there was marked decrease in histological alterations. Essentially, there was no liver steatosis, only hepatocellular ballooning. Scharlach stain was negative. The lucigenin-enhanced luminescence was reduced with vitamin C (1080 ± 330 cpm/mg/minx103) as compared to those Vitamin E and control (2247 ± 790; 2020 ± 407 cpm/mg/minx103, respectively) (p < 0.05). Serum levels of aminotransferases were unaltered by vitamin C or vitamin E. Conclusions 1) Vitamin C reduced oxidative stress and markedly inhibited the development of experimental liver steatosis induced by choline-deficient diet ; 2)Vitamin E neither prevented the development of fatty liver nor reduced the oxidative stress in this model.

Immunohistochemical evidence for myofibroblastlike cells associated with liver injury induced by Aflatoxin B1 in rainbow trout (Oncorhynchus mykiss)

In mammalian species, profibrogenic cells are activated to become myofibroblasts in response to liver damage. Few studies have examined hepatic myofibroblasts and their role in liver damage in teleosts. The aim of the present study was to investigate the involvement of myofibroblast-like cells in rainbow trout (Oncorhynchus mykiss) with hepatic damage induced by aflatoxin B1 (AFB1). Histopathological and immunohistochemical analyses characterized alterations in the liver stroma during the carcinogenic process. Anti-human a-smoothmuscle actin (SMA) and anti-human desmin primary antibodies were used in immunohistochemistry. Only the anti-SMA reagent labelled cells in trout liver. In the livers of control fish, only smooth muscle in blood vessels and around bile ducts was labelled. In the livers from AFB1-treated fish, SMA-positive cells were present in the stroma surrounding neoplastic lesions and in areas of desmoplastic reaction. These observations indicate that in teleosts, as in mammals, the myofibroblast-like cell is involved in fibrosis associated with liver injury. Chronic liver injury induced in trout by aflatoxin may provide a useful model system for study of the evolution of such mechanisms.

Effects of vitamin E supplementation on renal non-enzymatic antioxidants in young rats submitted to exhaustive exercise stress

Abstract Background Exercise stress was shown to increase oxidative stress in rats. It lacks reports of increased protection afforded by dietary antioxidant supplements against ROS production during exercise stress. We evaluated the effects of vitamin E supplementation on renal non-enzymatic antioxidants in young rats submitted to exhaustive exercise stress. Methods Wistar rats were divided into three groups: 1) control group; 2) exercise stress group and; 3) exercise stress + Vitamin E group. Rats from the group 3 were treated with gavage administration of 1 mL of Vitamin E (5 mg/kg) for seven consecutive days. Animals from groups 2 and 3 were submitted to a bout of swimming exhaustive exercise stress. Kidney samples were analyzed for Thiobarbituric Acid Reactive Substances to (TBARS) by malondialdehyde (MDA), reduced glutathione (GSH) and vitamin-E levels. Results The group treated with vitamin E and submitted to exercise stress presented the lowest levels of renal MDA (1: 0.16+0.02 mmmol/mgprot vs. 2: 0.34+0.07 mmmol/mgprot vs. 3: 0.1+0.01 mmmol/mgprot; p < 0.0001), the highest levels of renal GSH (1: 23+4 μmol/gprot vs. 2: 23+2 μmol/gprot vs. 3: 58+9 μmol/gprot; p < 0.0001) and the highest levels of renal vitamin E (1: 24+6 μM/gtissue vs. 2: 28+2 μM/gtissue vs. 3: 43+4 μM/gtissue; p < 0.001). Conclusion Vitamin E supplementation improved non-enzymatic antioxidant activity in young rats submitted to exhaustive exercise stress.

Effects of vitamin C supplementation on acute phase Chagas disease in experimentally infected mice with Trypanosoma cruzi QM1 strain

The tissue changes that occur in Chagas disease are related to the degree of oxidative stress and antioxidant capacity of affected tissue. Studies with vitamin C supplementation did not develop oxidative damage caused by Chagas disease in the host, but other studies cite the use of peroxiredoxins ascorbate - dependent on T. cruzi to offer protection against immune reaction. Based on these propositions, thirty "Swiss" mice were infected with T. cruzi QM1 strain and treated with two different vitamin C doses in order to study the parasitemia evolution, histopathological changes and lipid peroxidation biomarkers during the acute phase of Chagas disease. The results showed that the parasite clearance was greater in animals fed with vitamin C overdose. There were no significant differences regarding the biomarkers of lipid peroxidation and inflammatory process or the increase of myocardium in animals treated with the recommended dosage. The largest amount of parasite growth towards the end of the acute phase suggests the benefit of high doses of vitamin C for trypomastigotes. The supplementation doesn't influence the production of free radicals or the number of amastigote nests in the acute phase of Chagas disease.

Efficacy of the dietary histone deacetylase inhibitor butyrate alone or in combination with vitamin A against proliferation of MCF-7 human breast cancer cells

The combined treatment with histone deacetylase inhibitors (HDACi) and retinoids has been suggested as a potential epigenetic strategy for the control of cancer. In the present study, we investigated the effects of treatment with butyrate, a dietary HDACi, combined with vitamin A on MCF-7 human breast cancer cells. Cell proliferation was evaluated by the crystal violet staining method. MCF-7 cells were plated at 5 x 10(4) cells/mL and treated with butyrate (1 mM) alone or combined with vitamin A (10 µM) for 24 to 120 h. Cell proliferation inhibition was 34, 10 and 46% following treatment with butyrate, vitamin A and their combination, respectively, suggesting that vitamin A potentiated the inhibitory activities of butyrate. Furthermore, exposure to this short-chain fatty acid increased the level of histone H3K9 acetylation by 9.5-fold (Western blot), but not of H4K16, and increased the expression levels of p21WAF1 by 2.7-fold (Western blot) and of RARβ by 2.0-fold (quantitative real-time PCR). Our data show that RARβ may represent a molecular target for butyrate in breast cancer cells. Due to its effectiveness as a dietary HDACi, butyrate should be considered for use in combinatorial strategies with more active retinoids, especially in breast cancers in which RARβ is epigenetically altered.