931 resultados para Anti-oxidant activities
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The transition metal complexes of salicylhydrazone of anthranilhydrazide (H2L) were synthesised. The structures of metal complexes were characterized by various spectroscopic [IR, NMR, UV-Vis, EPR], thermal and other physicochemical methods. The single-crystal X-ray diffraction study of [Cu(HL)Cl]center dot H2O reveal its orthorhombic system with space group P2(1)2(1)2 and Z=4. The copper center has a distorted square planar geometry with ONO and Cl as the donor atoms. The ligand and its metal chelates have been screened for their antimicrobial and anti-tubercular activities using serial dilution method. Metal complexes in general have exhibited better antibacterial and antifungal activity than the free ligand and in few cases better than the standard used. Among the bacterial strains used, the complexes are highly potent against Gram-positive strains compared to Gram-negative. Anti-tubercular activity exhibited by the Co(II) complex is comparable with the standard used. (C) 2011 Elsevier B. V. All rights reserved.
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Heterogeneity in tumors has led to the development of combination therapies that enable enhanced cell death. Previously explored combination therapies mostly involved the use of bioactive molecules. In this work, we explored a non-conventional strategy of using carbon nanostructures (CNs) single walled carbon nanotube (SWNT) and graphene oxide (GO)] for potentiating the efficacy of a bioactive molecule paclitaxel (Tx)] for the treatment of lung cancer. The results demonstrated enhanced cell death following combination treatment of SWNT/GO and Tx indicating a synergistic effect. In addition, synergism was abrogated in the presence of an anti-oxidant, N-acetyl cysteine (NAC), and was therefore shown to be reactive oxygen species (ROS) dependent. It was further demonstrated using bromodeoxyuridine (BrdU) incorporation assay that treatment with CNs was associated with enhanced mitogen associated protein kinase (MAPK) activation that was ROS mediated. Hence, these results for the first time demonstrated the potential of SWNT/GO as co-therapeutic agents with Tx for the treatment of lung cancer.
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A prevalência da obesidade e da síndrome metabólica (SM) vem aumentando dramaticamente em jovens e está se tornando um problema de saúde pública na maioria dos países desenvolvidos e em desenvolvimento. Tanto a obesidade quanto a SM aumentam o número de pacientes expostos ao risco de doença cardiovascular. Estudos recentes mostram que uma redução na biodisponipilidade de óxido nítrico (NO) é um dos principais fatores que contribui para a ação deletéria da insulina nos vasos de pacientes adultos com obesidade e SM. O NO, potente vasodilatador e anti-agregante plaquetário, tem como precursor o aminoácido catiônico L-arginina que é transportado para o interior das plaquetas através do carreador y+L. Uma família de enzimas denominadas NO sintases (NOS) catalisa a oxidação da L-arginina em NO e L-citrulina e é composta de três isoformas: neuronal (nNOS), induzível (iNOS) e endotelial (eNOS). Os objetivos principais do presente estudo são de investigar diferentes etapas da via L-arginina-NO em plaquetas associando agregação plaquetária, concentração plasmática de L-arginina, estresse oxidativo, marcadores metabólicos, hormonais, clínicos e inflamatórios em pacientes adolescentes com obesidade e SM. Foram incluídos no estudo trinta adolescentes, sendo dez com obesidade, dez com SM, e dez controles saudáveis pareados por idade, sexo e classificação de Tanner (controles: n= 10, 15.6 0.7 anos; obesos: n= 10, 15 0.9 anos; SM: n= 10, 14.9 0.8 anos). O transporte de L-arginina (pmol/109céls/min) através do sistema y+L estava diminuído nos pacientes com SM (18.4 3.8) e obesidade (20.8 4.7), comparados aos controles (52.3 14.8). Houve uma correlação positiva do influxo de L-arginina via sistema y+L com os níveis de HDL-Colesterol. Por outro lado, foi encontrada uma correlação negativa do influxo de L-arginina com os níveis de insulina, os índices Homa IR, relacionado a RI, Homa Beta, relacionado a função da célula beta e também com os índices de Leptina. Em relação a produção de NO, a obesidade e a SM não afetaram a atividade e expressão das enzimas NOS. A atividade da superóxido dismutase (SOD), através da mensuração da inibição da auto-oxidação da adrenalina, mostrou diferença significativa nas plaquetas de pacientes com obesidade (4235 613,2 nMol/mg de proteína), quando comparada aos controles (1011 123,6 nmol/mg de proteína) e SM (1713 267,7 nmol/mg de proteína). A nível sistêmico, foi também evidenciada uma ativação desta enzima anti-oxidante no soro de pacientes obesos, em relação aos controles. A peroxidação lipídica avaliada pelas substâncias reativas ao ácido tiobarbitúrico (TBARS) estava inalterada no soro dos pacientes e controles. Estes resultados sugerem que o transporte de L-arginina diminuído nas plaquetas de adolescentes obesos e com SM pode ser um marcador precoce de disfunção plaquetária. A alteração desta via correlaciona-se com a resistência à insulina e hiperinsulinemia. A contribuição deste estudo e de fatores que possam ser precocemente identificados pode diminuir o risco cardiovascular na vida adulta desta população de pacientes.
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Despite advances in neonatal care, hypoxic-ischemic brain injury is still a serious clinical problem, which is responsible for many cases of perinatal mortality, cerebral palsy, motor impairment and cognitive deficits. Resveratrol, a natural polyphenol with important anti-oxidant and anti-inflammatory properties, is present in grapevines, peanuts and pomegranates. The aim of the present work was to evaluate the possible neuroprotective effect of resveratrol when administered before or immediately after a hypoxic-ischemic brain event in neonatal rats by analyzing brain damage, the mitochondrial status and long-term cognitive impairment. Our results indicate that pretreatment with resveratrol protects against brain damage, reducing infarct volume, preserving myelination and minimizing the astroglial reactive response. Moreover its neuroprotective effect was found to be long lasting, as behavioral outcomes were significantly improved at adulthood. We speculate that one of the mechanisms for this neuroprotection may be related to the maintenance of the mitochondrial inner membrane integrity and potential, and to the reduction of reactive oxygen species. Curiously, none of these protective features was observed when resveratrol was administered immediately after hypoxia-ischemia.
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Novos protótipos de fármacos estão constantemente a ser sintetizados e muitas estruturas cristalinas de outros ainda são desconhecidas. Tão importante quanto o planejamento e síntese de novos fármacos é a sua caracterização estrutural, uma vez que a sua estrutura (conformação) pode estar diretamente relacionada com a ação terapêutica. O uso da difração de raios X tem sido muito importante na determinação estrutural dos novos compostos sintetizados. Neste trabalho foi feita a determinação da estrutura de LASSBio-1755 com os dados de difração de raios X por policristais. Este composto foi sintetizado no Laboratório de Avaliação e Síntese de Substâncias Bioativas (LASSBio) da Universidade Federal do Rio de Janeiro. O composto LASSBio-1755 pertence a uma nova série de compostos cicloalquil-N-acilidrazônicos planejados para o desenvolvimento de protótipos com atividades antinociceptiva e anti-inflamatórios. Este composto cristalizou-se num sistema triclínico com grupo espacial (P ), com parâmetros de cela unitária a = 4,86647(9) Å, b = 9,3108(2) Å, c = 11,3402(2) Å, α = 106,649(1), β = 101,958(1), γ = 82,629(2) e V = 480,30(2) Å3. A estrutura cristalina de LASSBio-1755 consiste em duas fórmulas unitárias por cela unitária (Z = 2), acomodando uma molécula na unidade assimétrica (Z' = 1). O Método de Rietveld foi utilizado para refinar a estrutura cristalina e o indicador de qualidade do ajuste, bem como os fatores R foram, respectivamente: χ2 = 1,131, RBragg = 0,856%, Rwp =4,174% e o Rexp= 3,692%. As técnicas de calorimetria exploratória diferencial, termogravimetria e espectroscopia no infravermelho por transformada de Fourier também foram utilizadas para análise do composto LASSBio-1755 e os seus resultados corroboraram com os obtidos através da técnica de difração de raios X por policristais.
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Coral bleaching is a significant contributor to the worldwide degradation of coral reefs and is indicative of the termination of symbiosis between the coral host and its symbiotic algae (dinoflagellate; Symbiodinium sp. complex), usually by expulsion or xenophagy (symbiophagy) of its dinoflagellates. Herein, we provide evidence that during the earliest stages of environmentally induced bleaching, heat stress and light stress generate distinctly different pathomorphological changes in the chloroplasts, while a combined heat- and light-stress exposure induces both pathomorphologies; suggesting that these stressors act on the dinoflagellate by different mechanisms. Within the first 48 hours of a heat stress (32°C) under low-light conditions, heat stress induced decomposition of thylakoid structures before observation of extensive oxidative damage; thus it is the disorganization of the thylakoids that creates the conditions allowing photo-oxidative-stress. Conversely, during the first 48 hours of a light stress (2007 µmoles m−2 s−1 PAR) at 25°C, condensation or fusion of multiple thylakoid lamellae occurred coincidently with levels of oxidative damage products, implying that photo-oxidative stress causes the structural membrane damage within the chloroplasts. Exposure to combined heat- and light-stresses induced both pathomorphologies, confirming that these stressors acted on the dinoflagellate via different mechanisms. Within 72 hours of exposure to heat and/or light stresses, homeostatic processes (e.g., heat-shock protein and anti-oxidant enzyme response) were evident in the remaining intact dinoflagellates, regardless of the initiating stressor. Understanding the sequence of events during bleaching when triggered by different environmental stressors is important for predicting both severity and consequences of coral bleaching
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下载PDF阅读器利用多种柱层析方法,从法落海(Angelica apaensis)95%乙醇提取物中分离得到8个化合物.经IR、MS、NMR等波谱数据鉴定为氧化前胡素(oxypeucedanin,1)、氧化前胡素水合物(oxypeucedanin hydrate,2)、异欧芹属乙素(isoimperatorin,3)、白当归脑(byakangelicin,4)、白当归素(byakangelicol,5)、3'-O-acetylhamaudol (6)、(+)-9(Z),17-octadecadiene-12,14-diyne-1,11,16-triol(7)和9,17-octadecadiene-12,14-diyne-1,11,16-triol,1-acetate(8),其中,化合物6-8是首次从该植物中分离得到.我们对所有得到的8个化合物进行抗HIV活性分析,化合物1具有明显的抗HIV活性,其抑制合胞体形成的半数有效浓度(EC50)为1.6 ms/L,治疗指数(TI)为17.59.
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AIM: To identify the anti-human immunodeficiency virus type 1 (HIV-1) activities of alpha-momorcharin ( alpha-MMC) from Momordica charantia in acutely and chronically infected lymphocytes. METHODS: The anti-HIV activities of alpha-MMC were examined by 1) the inhibition of syncytia formation induced by HIV-1 III B; 2) reduction of p24 core antigen expression level and decrease in numbers of HIV antigen positive cells in acutely and chronically infected cultures. The cytotoxic effects of alpha-MMC was tested by trypan blue dye exclusion or colorimetric MTT assay. RESULTS: alpha-MMC was found to obviously inhibit HIV-1 III B-inducing C8166 syncytia formation and markedly reduced both expression of p24 core antigen and the numbers of HIV antigen positive cells in acutely but not chronically HTV-1-infected culture. The median effective concentration (EC50) in these assays were 0.016, 0.07, and 0.32 mg.L-1, respectively. CONCLUSION: alpha-MMC is a unique component of momorcharin with anti-HIV activity, and markedly inhibited HIV-1 replication in acutely but not chronically HIV-1-infected T-lymphocytes.
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C-Phycocyanin (C-PC) from blue-green algae has been reported to have various pharmacological characteristics, including antiinflammatory and anti-tumor activities. In this study, we expressed the beta-subunit of C-PC (ref to as C-POP) in Escherichia coli. We found that the recombinant C-PC/beta has anti-cancer properties. Under the treatment of 5 mu M of the recombinant C-PC/beta, four different cancer cell lines accrued high proliferation inhibition and apoptotic induction. Substantially, a lower response occurred in non-cancer cells. We investigated the mechanism by which C-PC/beta inhibits cancer cell proliferation and induces apoptosis. We found that the C-PC/beta interacts with membrane-associated beta-tubulin and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Under the treatment of the C-PC/beta, depolymerization of microtubules and actin-filaments were observed. The cells underwent apoptosis with an increase in caspase-3, and caspase-8 activities. The cell cycle was arrested at the G0/G1 phase under the treatment of C-PC/beta. In addition, the nuclear level of GAPDH decreased significantly. Decrease in the nuclear level of GAPDH prevents the cell cycle from entering into the S phase. Inhibition of cancer cell proliferation and induction of apoptosis may potentate the C-POP as a promising cancer prevention or therapy agent. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
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本论文对12个N-(取代苯磺酰)吲哚类化合物体外抗HIV活性进行了初步筛选,并选择其中活性最好的化合物N-(间硝基苯磺酰)-6-甲基吲哚,对其抗HIV 活性及作用机制进行深入研究。一、体外检测了12个N-(取代苯磺酰)吲哚类化合物对C8166和MT-4细胞的毒性、对HIV-1IIIB 感染C8166后诱导的合胞体形成的抑制及对HIV-1IIIB感染MT-4 细胞后的保护作用。结果发现多个化合物具有抑制HIV-1复制活性,特别是化合物N-(间硝基苯磺酰)-6-甲基吲哚,其对HIV-1IIIB诱导的合胞体形成的EC50和TI (Therapy index)值分别为0.26 μg/ml和543.78;对HIV-1IIIB急性感染的MT-4细胞也有很好的保护作用(TI值为104.23)。二、选择活性最强的化合物N-(间硝基苯磺酰)-6-甲基吲哚进行深入的抗 HIV活性研究。在细胞水平上,通过观察致感染细胞病变和HIV-1 p24抗原表达抑制实验(ELISA方法),采用3类多株HIV病毒株(实验株、临床分离株、耐药株)和3类多种细胞(人T淋巴细胞传代株、HIV-1慢性感染人T淋巴细胞株、人外周血单个核细胞)对化合物进行体外抗HIV活性进行系统评价,实验结果表明,化合物对不同来源的HIV-1病毒株都显示出很好抗HIV活性。同时,我们也研究了化合物抗HIV-2活性,发现该化合物并不能抑制HIV-2在C8166细胞中复制。三、在细胞毒性实验上,我们检测了N-(间硝基苯磺酰)-6-甲基吲哚对不同的细胞系和人外周血单个核细胞(PBMC)毒性作用,结果显示化合物的细胞毒性较低。四、在作用机制和靶点研究上,检测了化合物对感染与未感染细胞之间融合的抑制、对HIV-1急性感染C8166细胞及对HIV-1慢性感染H9细胞(H9/HIV-1IIIB)中病毒复制的阻断作用。结果显示,N-(间硝基苯磺酰)-6-甲基吲哚对急性感染细胞有很好抑制作用(EC50为0.52 μg/ml);但对感染与未感染细胞的融合(EC50为 46.40 μg/ml)和慢性感染H9细胞中病毒的复制没有抑制作用(EC50大于100 μg/ml)。提示化合物作用于HIV侵入细胞后到HIV DNA整合前这一阶段。其后对HIV-1逆转录酶活性的抑制情况进行了分析,发现N-(间硝基苯磺酰) -6-甲基吲哚对HIV-1逆转录酶(RT)有很好抑制作用。五、构效关系分析。我们对12 个N-(取代苯磺酰)吲哚类化合物进行了初步的构效关系研究,发现在N-benzenesulfonyl 环上连接一个吸电子基团(nitro group)比供电子基团(methyl group)有更强的抗HIV 活性,但当在indoles 环上连接吸电子基团(nitro group),抗HIV 活性反而受到抑制。以上实验数据显示N-(间硝基苯磺酰)-6-甲基吲哚是一个安全有效的抗 HIV-1 候选化合物,具有进一步研究价值。
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Phycobiliprotein is a photosynthetic antenna pigment found in cyanobacteria, rhodophytes, cryptophytes and certain dinoflagellates, which has been found to have anti-oxidative and anti-tumour activities. In this paper, a recombinant allophycocyanin (rAPC) had been expressed in Escherichia coli for anti-tumour effect. E. coli cells were cultured using glucose fed-batch method to achieve high cell densities. The biomass of rAPC was up to 3.52 g/L broth. The rAPC was purified from soluble E. coli cell lysate employing hydrophobic interaction chromatographic (HIC) method developed at the bench scale using 20 mL column. The process was performed at the pilot scale using 500 mL column for evaluation of scale-up. An amylose affinity column was used to improve the purity of final product in pilot scale purification. The purification process resulted in greater than 98% pure product and yielded up to 2.0 g/kg wet cells at the bench scale and 1.2 g/kg wet cells at the pilot scale. Peptide mapping was used to prove the identity of rAPC purified from bench scale and pilot scale process. Purified rAPC at the pilot scale was found to have remarkable inhibition on S-180 carcinoma in mice. (c) 2005 Elsevier Ltd. All rights reserved.
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坛紫菜(Porphyra haitanensis),属红藻门(Rhodophyta),红毛菜科(Bangiacease)紫菜属(Porphyra),是我国大规模养殖的重要经济海藻之一,主要产于我国南方沿海如福建、广东、浙江等地。紫菜作为中药,具有“补肾养心,利水消肿”的功效,实验室前期所作的工作表明,坛紫菜多糖具有良好的抗衰老作用。分子量对多糖生物活性有重大影响,本文以福建沿海的坛紫菜为原料,对坛紫菜多糖(P)的降解方法和该紫菜多糖的抗衰老活性与分子量的关系展开了研究。 本论文首次将植物生长发育过程中发生的抗坏血酸和过氧化氢反应体系应用于坛紫菜多糖的降解。抗坏血酸和过氧化氢的浓度及两者的比例是该降解方法的主要影响因素。采用该法制备了分子量分别为50、30、13、8.2和2.7 kD 的P1、P2、 P3、P4和P5五种产品。其中P1、P2和P3产品的红外图谱与原料多糖的红外图谱一致,表明这两种多糖的化学结构在降解过程中并未发生改变,而P4和P5样品的红外图谱显示该样品中出现了少量的羧基。 本论文还首次对各产物进行了抗氧化、免疫调节、抗疲劳、延长寿命、抗老年痴呆等活性的筛选与研究,具体结果如下: 采用化学法对五种降解多糖和原料多糖的抗氧化活性进行研究。结果表明分子量对坛紫菜多糖清除各种自由基能力的影响是不同的。降解之后,坛紫菜多糖清除超氧阴离子的能力有所下降,与金属离子的螯合能力几乎全部丧失,但是多糖清除羟基自由基的能力变化甚微。降解之后,坛紫菜多糖清除有机自由基的能力和还原能力显著提高,随分子量的降低这两种能力明显加强,其中P4样品清除有机自由基能力最强,而分子量最小的P5样品还原能力最突出。 通过测定T、B淋巴细胞增殖率考察了五种降解多糖和原料多糖的免疫调节作用。研究表明:不同分子量坛紫菜多糖均具有免疫调节作用,可显著促进小鼠脾脏T淋巴细胞增殖,显著抑制小鼠脾脏B淋巴细胞增殖。P2和P4样品效果强于其它降解产品和原料。 通过测定小鼠游泳和爬杆时间考察了三种降解多糖P1、P2、P4和原料多糖的耐疲劳作用。研究表明:坛紫菜多糖降解产品耐疲劳作用要优于原料多糖P。P1、P2和P4通过提高小鼠肝糖原储备从而达到显著延长小鼠爬杆时间和负重游泳时间的功效。 通过测定D. melanogaster果蝇寿命、热耐受时间和性活力考察了三种降解多糖P1、P2、P4和原料多糖对寿命及生命活力的影响。研究表明:分子量对坛紫菜多糖对果蝇的寿命和生命活力有很大影响。降解使坛紫菜原料多糖P对果蝇的延长寿命和提高生命活力作用得到加强。在果蝇正常代谢状态下,降解产品中分子量较大的P1和P2作用更显著,而在热应激状态下,降解产品中分子量较小的P4作用更突出。 采用小鼠侧脑室注射Aβ1-40致痴呆模型考察了样品P1改善认知功能的作用。研究表明:P1通过降低皮层和海马组织乙酰胆碱酯酶活性,显著提高乙酰胆碱转移酶的活性,有效改善痴呆小鼠的认知能力,使之水迷宫游泳时间缩短,使避暗潜伏期延长。 为探讨P1样品改善小鼠认知功能的作用机制,本文采用Aβ25-35损伤神经母细胞瘤株SH-SY5Y模型对P1样品的神经细胞的保护作用进行了研究。结果显示低浓度下P1对该损伤模型具有显著保护作用,高浓度下表现出显著的抑制作用。 本文的研究表明坛紫菜多糖在降解之后生物活性得到显著改善。分子量对坛紫菜多糖活性影响很大。总的看来,在体外实验中,分子量越低其体外抗氧化活性和免疫调节作用越显著,但是,在体内实验中,降解产品中分子量最大的P1样品能更有效地改善小鼠疲劳程度、延长果蝇的寿命及热耐受时间,P1样品还能显著改善痴呆小鼠记忆功能。不同分子量坛紫菜多糖体内和体外生物活性的这种差异还需要进行深入研究。
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Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas
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Sinapic acid (SA) is a nutraceutical with known anti-oxidant, anti-microbial, anti-inflammatory, anti-cancer, and anti-anxiety properties. Novel co-crystals of SA were prepared with co-formers belonging to the category of GRAS [isonicotinic acid (INC), nicotinamide (NIA)], non-GRAS [4-pyridinecarbonitrile (PYC)], and active pharmaceutical ingredients (APIs) [6-propyl-2-thiouracil (PTU)] list of compounds. Structural study based on the X-ray crystal structures revealed the intermolecular hydrogen-bonded interactions and molecular packing. The crystal structure of sinapic acid shows the anticipated acid-acid homodimer along with discrete hydrogen bonds between the acid carbonyl and the phenolic moiety. The robust acid-acid homodimer appears to be very stable and is retained in the structures of two co-crystals (SA[middle dot]NIA and SA[middle dot]PYC). In these cases, co-crystallization occurs via intermolecular phenol O-H[three dots, centered]Naromatic hydrogen bonds between the co-formers. In the SA[middle dot]PTU[middle dot]2MeCN co-crystal the acid-acid homodimer gives way to the anticipated acid-amide heterodimer, with the phenolic moiety of SA hydrogen-bonded to acetonitrile. Attempts at obtaining the desolvated co-crystal led to lattice breakdown, thus highlighting the importance of acetonitrile in the formation of the co-crystal. Among the co-crystals examined, SA[middle dot]INC (5 weeks), SA[middle dot]NIA (8 weeks) and SA[middle dot]PYC (5 weeks) were found to be stable under accelerated humidity conditions (40 [degree]C, 75% RH), whereas SA[middle dot]PTU[middle dot]2MeCN decomposed after one week into individual components due to solvent loss.
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Measures of prevention and control against polycyclic aromatic hydrocarbons (PAHs) focus on an official food control, a code of best practice to reduce PAHs levels by controlling industry and in the development of a chemopreventive strategy. Regulation (EU) 835/2011 establishes maximum levels of PAHs for each food group. In addition, Regulations (EU) 333/2007 and 836/2011 set up the methods of sampling and analysis for its official control. Scientific studies prove that the chemopreventive strategy is effective against these genotoxic compounds effects. Most chemopreventive compounds studied with proven protective effects against PAHs are found in fruit and vegetables.