Mary D Boudreau

U.S. Food and Drug Administration, Washington, D. C., DC, United States

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Publications (16)49.22 Total impact

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    ABSTRACT: A 2-year cancer bioassay in rodents with a preparation of Aloe vera whole leaf extract administered in drinking water showed clear evidence of carcinogenic activity. To provide insight into the identity and mechanisms associated with mutagenic components of the Aloe vera extracts, we used the mouse lymphoma assay to evaluate the mutagenicity of Aloe vera whole leaf extract (WLE) and Aloe vera decolorized whole leaf extract (WLD). The WLD extract was obtained by subjecting WLE to activated carbon-adsorption. HPLC analysis indicated that the decolorization process removed many components from the WLE extract, including anthraquinones. Both WLE and WLD extracts showed cytotoxic and mutagenic effects in mouse lymphoma cells but at different concentration ranges, and WLD induced about 3-fold higher levels of intracellular reactive oxygen species than WLE. Molecular analysis of mutant colonies from cells treated with WLE and WLD revealed that the primary type of damage from both treatments was largely due to chromosome mutations (deletions and/or mitotic recombination). The fact that the samples were mutagenic at different concentrations suggests that while some mutagenic components of WLE were removed by activated carbon filtration, components with pro-oxidant activity and mutagenic activity remained. The results demonstrate the utility of the mouse lymphoma assay as a tool to characterize the mutagenic activity of fractionated complex botanical mixtures to identify bioactive components.
    Toxicol. Res. 07/2014;
  • Mary D Boudreau
    Toxicological Sciences 03/2013; · 4.33 Impact Factor
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    ABSTRACT: Gold nanoparticles have received a great deal of interest due to their unique optical and catalytic properties and biomedical applications. Developing applications as well as assessing associated risks requires an understanding of the interactions between Au nanoparticles (NPs) and biologically active substances. In this paper, electron spin resonance spectroscopy (ESR) was used to investigate the catalytic activity of Au NPs in biologically relevant reactions. We report here that Au NPs can catalyze the rapid decomposition of hydrogen peroxide. Decomposition of hydrogen peroxide is accompanied by the formation of hydroxyl radicals at lower pH and oxygen at higher pH. In addition, we found that, mimicking SOD, Au NPs efficiently catalyze the decomposition of superoxide. These results demonstrate that Au NPs can act as SOD and catalase mimetics. Since reactive oxygen species are biologically relevant products being continuously generated in cells, these results obtained under conditions resembling different biological microenvironments may provide insights for evaluating risks associated with Au NPs.
    Biomaterials 10/2012; · 8.31 Impact Factor
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    ABSTRACT: Aloe barbadensis Miller (Aloe vera) is an herbal remedy promoted to treat a variety of illnesses; however, only limited data are available on the safety of this dietary supplement. Drinking water exposure of F344/N rats and B6C3F1 mice to an Aloe vera whole leaf extract (1%, 2%, and 3%) for 13 weeks resulted in goblet cell hyperplasia of the large intestine in both species. Based upon this observation, two-year drinking water studies were conducted to assess the carcinogenic potential of an Aloe vera whole leaf extract when administered to F344/N rats (48/sex/group) at 0.5%, 1%, and 1.5%, and B6C3F1 mice (48/sex/group) at 1%, 2%, and 3%. Compared to controls, survival was decreased in the 1.5% dose group of female rats. Treatment-related neoplasms and non-neoplastic lesions in both species were confined primarily to the large intestine. Incidences of adenomas and/or carcinomas of the ileo-cecal and cecal-colic junction, cecum, and the ascending and transverse colon were significantly higher than controls in male and female rats in the 1% and 1.5% dose groups. There were no neoplasms of the large intestine of mice or in the 0% or 0.5% dose groups of rats. Increased incidences of mucosa hyperplasia of the large intestine were observed in F344/N rats, and increased incidences of goblet cell hyperplasia of the large intestine occurred in B6C3F1 mice. These results indicate that Aloe vera whole leaf extract is an intestinal irritant in F344/N rats and B6C3F1 mice and a carcinogen of the large intestine in F344/N rats.
    Toxicological Sciences 09/2012; · 4.33 Impact Factor
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    ABSTRACT: Many of the chemical and biological effects of silver nanoparticles (Ag NPs) are attributed to the generation of reactive oxygen species (ROS). ESR spectroscopy was used to provide direct evidence for generating ROS during decomposition of H(2)O(2) assisted by Ag NPs. Hydroxyl radical formation was observed under acidic conditions and was accompanied by dissolution of Ag NPs. In contrast, evolution of O(2) was observed in alkaline solutions containing H(2)O(2) and Ag NPs; however, no net dissolution of Ag NPs was observed due to re-reduction of Ag(+) as evidenced by a cyclic reaction. Since H(2)O(2) is a biologically relevant product being continuously generated in cells, these results obtained under conditions mimicking different biological microenvironments may provide insights for finding new biomedical applications for Ag NPs and for risk assessment.
    Biomaterials 07/2012; 33(30):7547-55. · 8.31 Impact Factor
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    M Pogribna, J P Freeman, D Paine, M D Boudreau
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    ABSTRACT: To investigate the effect of Aloe vera whole leaf extract on pure and mixed human gut bacterial cultures by assessing the bacterial growth and changes in the production of short chain fatty acids. Bacteroides fragilis, Bifidobacterium infantis, and Eubacterium limosum were incubated with Aloe vera extracts [0%, 0.5%, 1%, 1.5% and 2%; (w/v)] for 24 and 48 h. Short chain fatty acids production was measured by gas chromatography/mass spectrometry analyses. A significant linear increase in growth response to Aloe vera supplementation was observed at 24 h for each of the bacterial cultures; however, only B. infantis and a mixed bacterial culture showed a significant positive linear dose response in growth at 48 h. In pure bacteria cultures, a significantly enhanced dose response to Aloe vera supplementation was observed in the production of acetic acid by B. infantis at 24 h and of butyric acid by E. limosum at 24 and 48 h. In the mixed bacterial culture, the production of propionic acid was reduced significantly at 24 and 48 h in a dose-dependent fashion, whereas butyric acid production showed a significant linear increase. The results indicated that Aloe vera possessed bacteriogenic activity in vitro and altered the production of acetic, butyric and propionic acids by micro-organisms selected for the study. The results of the study suggest that consumption of a dietary supplement, Aloe vera, may alter the production of short chain fatty acids by human intestinal microflora.
    Letters in Applied Microbiology 06/2008; 46(5):575-80. · 1.63 Impact Factor
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    ABSTRACT: Retinyl esters account for more than 70% of the endogenous vitamin A found in human skin, and retinyl palmitate is one of the retinyl esters in this pool. Human skin is also exposed to retinyl palmitate exogenously through the topical application of cosmetic and skin care products that contain retinyl palmitate. To date, there is limited information on the penetration and distribution of retinyl palmitate and vitamin A within in the skin. In this study, the accumulation of retinyl palmitate and generation of retinol in the skin of male and female SKH-1 mice that received repeated topical applications of creams containing 0.0%, 0.1%, 0.5%, 1.0%, 5.0%, 10%, or 13% of retinyl palmitate 5 days a week for a period of 13 weeks were studied. Because products containing retinyl palmitate are frequently applied to sun-exposed skin, and because it is well established that exposure to sunlight and UV light can alter cutaneous levels of retinoids, mice in this study were additionally exposed 5 days a week to simulated solar light. The results showed that retinyl palmitate diffused into the skin and was partially hydrolyzed to retinol. The levels of retinyl palmitate in the skin of mice that were administered retinyl palmitate cream were higher than control values, and levels of both retinyl palmitate and retinol increased with the application of higher concentrations of retinyl palmitate in the cream. Our results indicate that topically applied retinyl palmitate may alter the normal physiological levels of retinyl palmitate and retinol in the skin of SKH-1 mice and may have a significant impact on vitamin A homeostasis in the skin.
    Toxicology and Industrial Health 12/2007; 23(10):581-9. · 1.56 Impact Factor
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    ABSTRACT: Vitamin A (retinol), an essential human nutrient, plays an important role in cellular differentiation, regulation of epidermal cell growth and normal cell maintenance. In addition to these physiological roles, vitamin A has a rich photochemistry. Photoisomerization of vitamin A, involved in signal transduction for vision, has been extensively investigated. The biological effects of light-induced degradation of vitamin A and formation of reactive species are less understood and may be important for light-exposed tissues, such as the skin. Photochemical studies have demonstrated that excitation of retinol or its esters with UV light generates a number of reactive species including singlet oxygen and superoxide radical anion. These reactive oxygen species have been shown to damage a number of cellular targets, including lipids and DNA. Consistent with the potential for damaging DNA, retinyl palmitate has been shown to be photomutagenic in an in vitro test system. The results of mechanistic studies were consistent with mutagenesis through oxidative damage. Vitamin A in the skin resides in a complex environment that in many ways is very different from the chemical environment in solution and in in vitro test systems. Relevant clinical studies or studies in animal models are therefore needed to establish whether the pro-oxidant activity of photoexcited vitamin A is observed in vivo, and to assess the related risks.
    Photochemistry and Photobiology 03/2007; 83(2):409-24. · 2.29 Impact Factor
  • Qingsu Xia, Jun Jie Yin, Peter P Fu, Mary D Boudreau
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    ABSTRACT: Aloe vera whole leaf extracts are incorporated into a wide variety of topically applied commercial products. Aloe vera whole leaf extracts may contain anthraquinones, which have been shown to generate reactive oxygen species in the presence of ultraviolet A (UVA) light. Exposure to UVA light alone can also generate reactive oxygen species and is associated with photo-damaged and photo-aged skin in humans. This paper examines the photochemical properties of two Aloe vera whole leaf extracts that differed in their anthraquinone content. In the presence of methyl linoleate, the UVA irradiation of Aloe vera leaf extracts induced lipid peroxidation. The amounts of lipid peroxides formed were higher in the Aloe vera leaf extract that contained lower amounts of anthraquinones. Superoxide dismutase and sodium azide inhibited and deuterium oxide enhanced the formation of lipid peroxides, suggesting that singlet oxygen and superoxide were involved in the mechanism. Spin trapping electron spin resonance (ESR) spectroscopy was used to investigate the generation of free radicals by the UVA photo-irradiated Aloe vera plant extracts. ESR measurements indicated that the UVA photo-irradiation of Aloe vera plant extracts produced carbon-centered free radicals. These results suggest that humans exposed to products that contain Aloe vera whole leaf extracts may have enhanced sensitivity to ultraviolet light.
    Toxicology Letters 02/2007; 168(2):165-75. · 3.15 Impact Factor
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    ABSTRACT: The skin is similar to other organs in how it absorbs, stores, and metabolizes vitamin A. However, because of the anatomical location of skin and the specialized physiological roles it plays, there are ways in which the skin is rather unique. The stratified structure of the epidermis results from the orchestration of retinoid-influenced cellular division and differentiation. Similarly, many of the physiological responses of the skin, such as dermal aging, immune defense, and wound healing, are significantly affected by retinoids. While much is known about the molecular events through which retinoids affect the skin's responses, more remains to be learned. Interest in the effects of retinol, retinyl palmitate, and other retinoids on the skin, fueled in part by the promise of improved dermatologic and cosmetic products, will undoubtedly make the effects of retinoids on skin a subject for continued intense investigation.
    Vitamins & Hormones 02/2007; 75:223-56. · 2.30 Impact Factor
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    ABSTRACT: We have previously reported that photoirradiation of retinyl palmitate (RP), a storage and ester form of vitamin A (retinol), with UVA light resulted in the formation of photodecomposition products, generation of reactive oxygen species, and induction of lipid peroxidation. In this paper, we report our results following the photoirradiation of RP in ethanol by an UV lamp with approximately equal UVA and UVB light. The photodecomposition products were separated by reversed-phase HPLC and characterized spectroscopically by comparison with authentic standards. The identified products include: 4-keto-RP, 11-ethoxy-12-hydroxy-RP, 13-ethoxy-14-hydroxy-RP, anhydroretinol (AR), and trans- and cis-15-ethoxy-AR. Photoirradiation of RP in the presence of a lipid, methyl linoleate, resulted in induction of lipid peroxidation. Lipid peroxidation was inhibited when sodium azide was present during photoirradiation which suggests free radicals were formed. Our results demonstrate that, similar to irradiation with UVA light, RP can act as a photosensitizer leading to free radical formation and induction of lipid peroxidation following irradiation with UVB light.
    International journal of environmental research and public health 07/2006; 3(2):185-90. · 1.61 Impact Factor
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    ABSTRACT: Retinyl esters are the storage form of vitamin A in skin, and retinyl palmitate (RP) accounts for the majority of the retinyl esters endogenously formed in skin. RP is also obtained exogenously through the topical application of cosmetic and skin care products that contain RP. There is limited information on the penetration and distribution of RP and vitamin A within the stratified layers of the skin. The purpose of these studies was to determine the time course for accumulation and disappearance of RP and retinol in the stratified layers of skin from female SKH-1 mice that received single or repeated topical applications of creams containing 0.5 or 2% of RP. We developed an HPLC method with detection limits of 5.94 and 1.62 ng, to simultaneously quantify the amount of RP and retinol, respectively, in skin samples. Our results showed that RP rapidly diffuses into the stratum corneum and epidermal skin layers within 24 h following the application of RP-containing creams. Of the three skin layers, the highest level of RP and retinol per weight unit (ng/mg) at all time points was found in the epidermis. Levels of RP and retinol were lowest in the dermal layer and intermediate in the stratum corneum. The levels of RP and retinol in the separated skin layers and in the intact skin decreased with time, but levels of RP remained higher than control values for a period of up to 18 days. Our results indicate that the application of RP to mouse skin alters the normal physiological levels of RP and retinol in the skin.
    Toxicology and Industrial Health 06/2006; 22(4):181-91. · 1.56 Impact Factor
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    ABSTRACT: We have previously reported that photoirradiation of retinyl palmitate (RP) in ethanol with UVA light results in the formation of photodecomposition products, including 5,6-epoxy-RP and anhydroretinol (AR). Photoirradiation in the presence of a lipid, methyl linoleate, induced lipid peroxidation, suggesting that reactive oxygen species (ROS) are formed. In the present study, we employ an electron spin resonance (ESR) spin trap technique to provide direct evidence as to whether or not photoirradiation of RP by UVA light produces ROS. Photoirradiation of RP by UVA in the presence of 2,2,6,6-tetramethylpiperidine (TEMP), a specific probe for singlet oxygen, resulted in the formation of TEMPO, indicating that singlet oxygen was generated. Both 5,5-dimethyl N-oxide pyrroline (DMPO) and 5-tert-butoxycarbonyl 5-methyl-1-pyrroline N-oxide (BMPO) are specific probes for superoxide. When photoirradiation of RP was conducted in the presence of the DMPO or BMPO, ESR signals for DMPO-*OOH or BMPO-*OOH were obtained. These results unambiguously confirmed the formation of superoxide radical anion. Consistent with a free radical mechanism, there was a near complete and time-dependent photodecomposition of RP and its photodecomposition products. ESR studies on the photoirradiation of 5,6-epoxy-RP and AR indicate that these compounds exhibit similar photosensitizing activities as RP under UVA light.
    Toxicology Letters 06/2006; 163(1):30-43. · 3.15 Impact Factor
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    ABSTRACT: Vitamin A (retinol) regulates many biological functions, including epidermal cell growth. Retinyl palmitate (RP) is the major esterified form of retinol and the predominant component of retinoids in the skin; however, how endogenous levels of RP and retinol in the skin are affected by the age of the animal remains unknown. Furthermore, the levels of retinol and RP in the various skin layers - the stratum corneum, epidermis and dermis of skin - have not been reported. In this paper, we report the development of a convenient method for separation of the skin from SKH-1 female mice into the stratum corneum, epidermis, and dermis and the determination of the levels of RP and retinol in the three fractions by HPLC analysis. The total quantities of RP and retinol from the stratum corneum, epidermis, and dermis are comparable to those extracted from the same amount of intact skin from the same mouse. There was an age-related effect on the levels of RP and retinol in the skin and liver of female mice. An age-related effect was also observed in the stratum corneum, epidermis, and dermis. The levels of RP and retinol were highest in the epidermis of 20-week-old mice, and decreased when the age increased to 60- and 68-weeks. The total amount of RP at 20 weeks of age was found to be 1.52 ng/mg skin, and decreased about 4-fold at 60- and 68-weeks of age. A similar trend was found for the effects of age on the levels of retinol.
    Toxicology and Industrial Health 05/2006; 22(3):103-12. · 1.56 Impact Factor
  • Mary D Boudreau, Frederick A Beland
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    ABSTRACT: Aloe barbadensis (Miller), Aloe vera, has a long history of use as a topical and oral therapeutic. The plant is the source of two products, gel and latex, which are obtained from its fleshy leaves. Aloe vera products contain multiple constituents with potential biological and toxicological activities, yet the active components elude definition. Ingestion of Aloe vera is associated with diarrhea, electrolyte imbalance, kidney dysfunction, and conventional drug interactions; episodes of contact dermatitis, erythema, and phototoxicity have been reported from topical applications. This review examines the botany, physical and chemical properties, and biological activities of the Aloe vera plant.
    Journal of Environmental Science and Health Part C 05/2006; 24(1):103-54. · 3.57 Impact Factor
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    ABSTRACT: Sunlight is a known human carcinogen. Many cosmetics contain retinoid-based compounds, such as retinyl palmitate (RP), either to protect the skin or to stimulate skin responses that will correct skin damaged by sunlight. However, little is known about the photodecomposition of some retinoids and the toxicity of these retinoids and their sunlight-induced photodecomposition products on skin. Thus, studies are required to test whether topical application of retinoids enhances the phototoxicity and photocarcinogenicity of sunlight and UV light. Mechanistic studies are needed to provide insight into the disposition of retinoids in vitro and on the skin, and to test thoroughly whether genotoxic damage by UV-induced radicals may participate in any toxicity of topically applied retinoids in the presence of UV light. This paper reports the update information and our experimental results on photostability, photoreactions, and phototoxicity of the natural retinoids including retinol (ROH), retinal, retinoid acid (RA), retinyl acetate, and RP (Figure 1).
    International journal of environmental research and public health 05/2005; 2(1):147-55. · 1.61 Impact Factor

Publication Stats

183 Citations
49.22 Total Impact Points

Institutions

  • 2005–2013
    • U.S. Food and Drug Administration
      • • Division of Biochemical Toxicology
      • • National Center for Toxicological Research
      Washington, D. C., DC, United States
  • 2006
    • U.S. Department of Health and Human Services
      Washington, Washington, D.C., United States