Spelling suggestions: "subject:"aristolochic acids"" "subject:"ristolochic acids""
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Chemistry of the aristolochic acids Part I. Isolation and structure elucidation of phenanthroic acid derivatives from Aristolochia indica L. ; Part II. Synthetic approaches to 1-nitro-10-phenanthroic acids as potential tumor inhibitors. /Merianos, John James, January 1966 (has links)
Thesis (Ph. D.)--University of Wisconsin--Madison, 1966. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.
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Histomorfološke, imunohistohemijske i biohemijske karakteristike oštećenja bubrega kod miševa u modelu toksične nefropatije izazvane aristolohičnom kiselinom I / Histolomorphological, immunohistochemical and biochemical characteristics of kidney injury in mouse model of aristolochic acid nephropathyMiljković Dejan 18 February 2019 (has links)
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5.4pt;mso-para-margin-top:0in;mso-para-margin-right:0in;mso-para-margin-bottom:10.0pt;mso-para-margin-left:0in;line-height:115%;mso-pagination:widow-orphan;font-size:11.0pt;font-family:"Calibri","sans-serif";mso-ascii-font-family:Calibri;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:"Times New Roman";mso-fareast-theme-font:minor-fareast;mso-hansi-font-family:Calibri;mso-hansi-theme-font:minor-latin;}</style><![endif]--></p><p class="MsoNormal" style="text-align:justify">Uvod: Aristolohična kiselina I je nefrotoksična i kancerogena supstanca koja je odgovorna za nefropatiju koja nastaje usled korišćenja herbalnih preparata i čajeva za mršavljenje. S obzirom da se ova supstanca može naći u korovskim biljkama, smatra se jednim od glavnih ekotoksikoloških uzroka za nastanak balkanske endemske nefropatije čiji definitivan uzrok još uvek nije otkriven. Toksičnost ove supstance je dokazana na brojnim animalnim modelima, međutim mehanizmi koji dovode do oštećenja bubrežnog parenhima još u potpunosti nisu razjašnjeni.<span style="mso-spacerun:yes"> </span>Cilj: Doktorska disertacija je koncipirana sa ciljem da se utvrdi uticaj toksičnog jedinjenja aristolohične kiseline I na histopatološke i imunohistohemijske karakteristike tubulointersticijuma i glomerula bubrega kod miševa, kao i na biohemijske parametre krvi i urina koji ukazuju na oštećenje bubrega. Materijal i metode: U ekperimentu je korišćeno 64 miša soja NMRI koji su podeljeni u tri grupe: eksperimentalna grupa (n=32) koja je dobijala aristolohičnu kiselinu I rastvorenu u polietilen glikolu (2,5% PEG 400) u dozi od 10 mg/kg telesne mase, negativna kontrolna grupa koja je dobijala 2,5% PEG 400 (n=16) i kontrolna grupa koja je dobijala fiziološki rastovor (n=16). Sve životinje su tretirane intraperitonealno svakodnevno tokom sedam dana. Tokom eksperimenta 8., 17., 29. i 59. dana sakupljan je dvadesetčetvoročasovni urin 8 životinja iz eksperimentalne grupe, 4 životinje iz negativne kontrolne i 4 životinje iz kontrolne grupe. Životinje su žrtvovane 9., 18., 30. i 60. dana, uzeta im je krv, dok su bubrezi posebno odvojeni radi histopatološke analize. Na bubrežnom tkivu sprovedene su histohemijske, imunohistohemijske i morfometrijske analize, dok su na uzorcima seruma i urina sprovedene biohemijske analize. Dobijeni rezultati su testirani adekvatnim statističkim metodama i prikazani su tabelarno i grafički. Rezultati: Nefrotoksin aristolohična kiselina I nakon 7 dana aplikacije izaziva značajno oštećenje bubrežnog parenhima. Pri aplikaciji 2,5% PEG 400 i fiziološkog rastvora ne dolazi do vidljivog oštećenja bubrežnog parenhima. Histopatološku sliku u ranoj fazi eksperimenta (9. i 18. dan) karakteriše akutna tubulska nekroza proksimalnih tubula. U kasnijoj fazi (30. i 60. dana) uočava se histopatološka slika hroničnog intersticijalnog nefritisa sa obilnim mononuklearnim ćelijskim infiltratima limfocitnog porekla kao i postojanje blage intersticijalne fibroze. Kod eksperimentalnih životinja je morfometrijskim metodama utvrđen veći stepen bubrežnog oštećenja tubulointersticijuma i smanjen broj podocita u glomerulu u odnosu na kontrolne grupe. Biohemijske analize kod većine eksperimentalnih životinja su pokazale veće koncentracije serumske uree nego kod kontrolnih grupa. Takođe je dokazana albuminurija u kasnijoj fazi eksperimenta koja je veća kod životinja izloženih aristolohičnoj kiselini I nego kod životinja iz kontrolnih grupa. Zaključak: Korišćenjem morfometrijskih metoda u okviru histopatoloških i imunohistohemijskih ispitivanja, uz adekvatne biohemijske analize, može se zaključiti da je aristolohična kiselina I izuzetno nefrotoksično jedinjenje koje izaziva izrazite<span style="mso-spacerun:yes"> </span>promene tubulointersticijuma i glomerula. Podaci ovog istraživanja predstavljaju polaznu osnovu za dalja istraživanja dijagnostike u ranoj fazi nefropatija izazvanih aristolohičnim kiselinama.<span style="mso-spacerun:yes"> </span></p> / <p>Introduction: Aristolochic acid I is a nephrotoxic and carcinogenic substance responsible for nephropathy caused by the use of herbal preparations and teas for slimminng regimen. Since this substance can be found in plants, it is considered one of the major ecotoxicological causes for the emergence of balkan endemic nephropathy whose definitive cause has not yet been revealed. The toxicity of this substance has been proven on numerous animal models, but pathophysiological mechanisms of kidney injury still remain unclear. Aim: The doctoral dissertation was designed to determine the influence of aristolochic acid on the histopathological and immunohistochemical characteristics of tubulointerstitium and glomerulus in mice, as well as the biochemical parameters of blood and urine that indicate kidney injury. Material and methods: For this study, 64 mouse of NMRI strain is used. They are divided into three groups: an experimental group (n=32) that received aristolochic acid I dissolved in polyethylene glycol (2.5% PEG 400) at a dose of 10 mg/kg of body weight, a negative control group that received 2.5% PEG 400 (n=16) and a control group that received only saline (n=16). All animals were treated intraperitoneally daily for seven days. During the experiment on the 8th, 17th, 29th and 59th day, twenty-four-hour urine was collected from 8 animals from the experimental group, 4 animals from the negative control and 4 animals from the control group. Animals were sacrificed on the 9th, 18th, 30th and 60th days, their blood was taken, while the kidneys were taken for histopathological analysis. Histochemical, immunohistochemical and morphometric analyzes were performed on renal tissue, while biochemical analyzes were performed on serum and urine samples. Obtained results were tested with adequate statistical methods and presented in a tables and graphs. Results: After 7 days of application nefrotoxin aristolochic acid I causes significant kidney injury. After application of 2.5% PEG 400 and saline, there was no visible damage to kidney parenchyma. Histopathological changes at the early stage of the experiment (9th and 18th day) were characterized by acute tubular necrosis of proximal tubules. At a later stage (30th and 60th day), chronic interstitial nephritis was observed in kidneys, with abundant mononuclear cell infiltrates in interstitium and presence of mild interstitial fibrosis. In experimental animals, a higher tubulointerstitial score of kidney injury and a decrease in the number of the podocytes in glomerulus were determined by morphometric methods, compared to the control groups. Biochemical analyzes in most experimental animals showed higher blood urea nitrogen concentrations than in control groups. High concentration of albumin in urine can be found in later stages of the experiment, and those concentrations were higher in animals exposed to aristolochic acid I than in animals from control groups. Conclusion: Using morphometric, histopathological and immunohistochemical methods, with adequate biochemical analysis, aristolochic acid I is proven to be an extremely nephrotoxic compound that causes drastic changes in tubulointerstitium and glomeruli of kidney parenhyma. Data from this study can be used for further research into early diagnosis of aristolochic acid nephropathy.</p>
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Studium metabolizmu karcinogenní a nefrotoxické přírodní látky aristolochové kyseliny II / Study of metabolism carcinogenic and nephrotoxic natural compound aristolochic acid IIMartináková, Lenka January 2019 (has links)
Aristolochic acids (AA) have been considered as toxicants of plants which were found in plants of the family Aristolochiaceae. The most abundant acids in mentioned plants are aristolochic acid I (AAI) and aristolochic acid II (AAII). AA have been considered as causes kidney disease called Aristolochic acid nephropathy (AAN). AAN was initially discovered in patients of one Belgian clinic in Brussels specialized on treatment of patients leading to a decrease in their body weight. The first name of this disease was Chinese herb nephropathy (CHN). Later, it was discovered that one component of herbal preparation was changed by a mistake with the Aristolochiaceae plant. The second type of renal disease caused by AA was discovered in populations of countries along the Danube river, called as Balkan endemic nephropathy (BEN), which was probably caused by the contamination of grains with plants containing AA. These renal diseases (AAN and BEN) are often associated with development of upper urothelial cancer (UUC). AA (AAI + AAII) in organisms are subject to biotransformation leading to its reductive activation or oxidative detoxification. Both cytosolic enzymes [NAD(P)H:quinone oxidoreductase] and microsomal enzymes [cytochromes P450, NADPH:cytochrome P450 reductase] participate in their reduction. The...
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Apport de la chromatographie de partage centrifuge à l'étude phytochimique de 3 plantes utilisées en médecine traditionnelle soudanaise / The contribution of centrifugal partition chromatography to the phytochemical study of three plants used in traditional Sudanese medicineAlamin, Abdelgadir 09 December 2016 (has links)
Ce travail de thèse est une contribution à l’étude phytochimique par Chromatographie de Partage Centrifuge (CPC), de trois plantes utilisées en médecine traditionnelle au Soudan : Aristolochia bracteolata (plante entière), Ziziphus spina-christi (feuilles) et Hydnora abyssinica (rhizomes). Ce travail a permis de mettre au point trois méthodologies de purification par CPC, applicables au fractionnement des acides aristolochiques, des flavonoïdes ou des proanthocyanidols (PAC). Dans ce contexte, la première partie de ce manuscrit est consacrée aux notions générales portant sur la CPC. La deuxième partie porte sur l’étude d’Aristolochia bracteolata. Cette plante est utilisée en médecine traditionnelle, malgré la présence d'acides aristolochiques qui confèrent une néphrotoxicité élevée. Ce travail a permis de mettre au point une méthode innovante pour l’isolement et la purification, avec un très haut niveau de pureté, des acides aristolochiques I, II et IIIa à partir d’un extrait brut, en une étape par CPC en mode d’échange d’ions forts (SIX-CPC). L’acide aristolochique IIIa n’avait jamais été décrit dans cette plante auparavant. Ces résultats ont fait l’objet d’une publication en 2015 dans Separation and Purification Technology. Dans la troisième partie de cette thèse, la CPC a été appliquée à l’isolement de flavonosides présents dans Z. spina-christi. Nous appuyant sur l’expérience du laboratoire dans l’extraction par CPC des flavonosides du Ginkgo biloba, nous proposons une méthodologie de purification utilisant les systèmes de solvant biphasiques EtOAc/n-BuOH/MeOH/H2O et EtOAc/n-BuOH/H2O à différents ratios en fonction de la polarité des flavonosides. Dans la dernière partie, l’étude phytochimique de Hydnora abyssinica a mis en évidence la présence de PACs, polymères de hauts poids moléculaires de flavanols. La méthodologie de fractionnement CPC, précédée d’un pré-fractionnement sur résine LH-20, a permis l’isolement pour la première fois dans cette plante de la katsumadine et du rhodioloside. / This work was a contribution to the phytochemical study of three Sudanese medicinal plants: Aristolochia bracteolata (Whole plant), Ziziphus spina-christi (Leaves) and Hydnora abyssinica (Rhizomes). The specificity of this research program was to emphasize the application of Centrifugal Partition Chromatography (CPC) for the fractionation of these plants. Three specific CPC methodologies were developed for the purification of either aristolochic acids, flavonoids or proanthocyanidins (PACs). In this context, the first part of this manuscript was devoted to the presentation of the CPC methodology. The second part focused on the fractionation of crude extract of Aristolochia bracteolata. This plant is used in traditional medicine, in spite of the presence of aristolochic acids that confer a high nephrotoxicity. In this work was developed an innovating procedure for the isolation and purification in high purity of aristolochic acids I, II and IIIa, in one step from crude extract, using Strong Ions eXchange CPC (SIX-CPC). These results were published in 2015 in Separation and Purification Technology. In the third part, the flavonosides present in Z. spina-christi were isolated using CPC, either in normal or reverse elution mode, using two phases solvent systems EtOAc/n-BuOH/MeOH/H2O or EtOAc/n-BuOH/H2O with different ratios. In the last part, the phytochemical study of Hydnora abyssinica led to the fractionation of PACs, polymers of high molecular weight of flavanols. The CPC fractionation methodology, preceded by LH-20 resin pre-fractionation, allowed the isolation of katsumadine and rhodioloside.
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