The DOI matches its Crossref record; 62 of the 63 references it cites were found in a registry or an index.
Hyperuricemia and xanthine oxidase in preeclampsia, revisited
Abstract
Hyperuricemia is associated with the severity of preeclampsia and with fetal outcome. Traditionally the high uric acid concentration in preeclampsia has been attributed soley to renal dysfunction. Preeclampsia is also characterized by increased free radical formation and elevated oxidative stress. Xanthine dehydrogenase/oxidase produces uric acid. Xanthine dehydrogenase/oxidase is present as two isoforms in vivo. Uric acid production is coupled with formation of reactive oxygen species when the enzyme is in the oxidase form. Several factors can increase the holoenzyme activity and the conversion of xanthine dehydrogenase/oxidase to its oxidase form. These factors include hypoxia-reperfusion, cytokines, and increased substrate availability (xanthine and hypoxanthine). Preeclampsia is characterized by hyperuricemia and signs of increased formation of reactive oxygen species and decreased levels of antioxidants. Preeclampsia is also characterized by shallow implantation, producing a relatively hypoxic maternal-fetal interface, and increased turnover of trophoblast tissue, which can result in higher xanthine and hypoxanthine concentrations and higher levels of circulating cytokines. These mechanisms can lead to increased production of uric acid and free radicals and contribute to the hyperuricemia and increased oxidative stress present in preeclampsia.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Gui et al.(75) suggested that metformin reduced the rate of gestational hypertension because of its effects on endothelial function and its decrease in the production of reactive oxygen species, the two mechanisms implicated in the pathophysiology of preeclampsia(84–94).”
From Metformin, the Aspirin of the 21st Century: Its Role in Gestational Diabetes Mellitus, Prevention of Preeclampsia and Cancer, and the Promotion of Longevity (2017) · cites this paper as [89]
In the citing paper
“Torbergsen et al. suggested that these women developed preeclampsia because their dysfunctional mitochondria could not meet the increased energy demands of pregnancy, and the failure of adequate cellular energy production led to an accumulation of ADP, which is able to mediate most of the changes seen in preeclampsia(89, 197)”
From Metformin, the Aspirin of the 21st Century: Its Role in Gestational Diabetes Mellitus, Prevention of Preeclampsia and Cancer, and the Promotion of Longevity (2017) · cites this paper as [89]
In the citing paper
“ADP is a vasoconstrictor, causes platelet aggregation, and breaks down to uric acid.”
From Metformin, the Aspirin of the 21st Century: Its Role in Gestational Diabetes Mellitus, Prevention of Preeclampsia and Cancer, and the Promotion of Longevity (2017) · cites this paper as [89]
Citations
Cites
Harrison's Principles of Internal Medicine.
(1988) · Annals of Internal Medicine · doi:10.7326/0003-4819-108-3-499_2 · Cited by 12,528
Oxygen-Derived Free Radicals in Postischemic Tissue Injury
Epstein, F. H., & McCord, J. M. (1985) · New England Journal of Medicine · doi:10.1056/nejm198501173120305 · Cited by 5,399
The Pathology of the Human Placenta
Benirschke, K., & Driscoll, S. G. (1967) · Springer eBooks · doi:10.1007/978-1-4612-9809-0 · Cited by 2,253
Xanthine oxidase as a source of free radical damage in myocardial ischemia
CHAMBERS, D., PARKS, D., PATTERSON, G., ROY, R., MCCORD, J., YOSHIDA, S., PARMLEY, L., & DOWNEY, J. (1985) · Journal of Molecular and Cellular Cardiology · doi:10.1016/s0022-2828(85)80017-1 · Cited by 672
Xanthine oxidase: biochemistry, distribution and physiology.
Parks, D. A., & Granger, D. N. (1986) · PubMed · Cited by 638
Lipid peroxidation in pregnancy: New perspectives on preeclampsia
Hubel, C. A., Roberts, J. M., Taylor, R. N., Musci, T. J., Rogers, G. M., & McLaughlin, M. K. (1989) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(89)90778-3 · Cited by 445
Self-citationLocalization of xanthine oxidase in mammary-gland epithelium and capillary endothelium
Jarasch, E.-D., Gründ, C., Bruder, G., Heid, H., Keenan, T. W., & Franke, W. W. (1981) · Cell · doi:10.1016/0092-8674(81)90232-4 · Cited by 440
Roberts, J. M., Taylor, R. N., & Goldfien, A. (1991) · American Journal of Hypertension · doi:10.1093/ajh/4.8.700 · Cited by 389
Self-citationThe Role of Oxygen Radicals in Human Disease, with Particular Reference to the Vascular System
Halliwell, B. B. (2009) · Haemostasis · doi:10.1159/000216921 · Cited by 358
EMBOLISM TO THE LUNGS BY TROPHOBLAST
Attwood, H. D., & Park, W. W. (1961) · BJOG An International Journal of Obstetrics & Gynaecology · doi:10.1111/j.1471-0528.1961.tb02778.x · Cited by 267
PLASMA-URATE MEASUREMENTS IN PREDICTING FETAL DEATH IN HYPERTENSIVE PREGNANCY
Redman, C. W. G., Beilin, L. J., Bonnar, J., & Wilkinson, R. H. (1976) · The Lancet · doi:10.1016/s0140-6736(76)93024-5 · Cited by 264
Mediator‐induced activation of xanthine oxidase in endothelial cells
Friedl, H. P., Till, G. O., Ryan, U. S., & Ward, P. A. (1989) · The FASEB Journal · doi:10.1096/fasebj.3.13.2806779 · Cited by 218
Hypoxanthine as a Measurement of Hypoxia
Saugstad, O. D. (1975) · Pediatric Research · doi:10.1203/00006450-197504000-00002 · Cited by 218
Binding of human xanthine oxidase to sulphated glycosaminoglycans on the endothelial-cell surface
Adachi, T., Fukushima, T., Usami, Y., & Hirano, K. (1993) · Biochemical Journal · doi:10.1042/bj2890523 · Cited by 213
Trophoblast deportation in pre‐eclamptic pregnancy
Chua, S., WILKINS, T., SARGENT, I. L., & Redman, C. W. G. (1991) · BJOG An International Journal of Obstetrics & Gynaecology · doi:10.1111/j.1471-0528.1991.tb15334.x · Cited by 188
Circulating xanthine oxidase: potential mediator of ischemic injury
Yokoyama, Y., Beckman, J. S., Beckman, T. K., Wheat, J. K., Cash, T., Freeman, B. Α., & Parks, D. A. (1990) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1990.258.4.g564 · Cited by 188
Lipid Peroxidation in Pregnancy
Walsh, S. W. (1994) · Hypertension in Pregnancy · doi:10.3109/10641959409084168 · Cited by 176
A STUDY OF THE VESSELS OF THE PLACENTAL BED IN NORMOTENSIVE AND HYPERTENSIVE WOMEN
Dixon, H. G., & Robertson, W. B. (1958) · BJOG An International Journal of Obstetrics & Gynaecology · doi:10.1111/j.1471-0528.1958.tb08876.x · Cited by 172
Sera antioxidant activity in uncomplicated and preeclamptic pregnancies
Davidge, S. T., Hubel, C. A., Brayden, R. D., Capeless, E. C., & McLaughlin, M. K. (1993) · International Journal of Gynecology & Obstetrics · doi:10.1016/0020-7292(93)90421-r · Cited by 163
Self-citationDupont, G. P., Huecksteadt, T. P., Marshall, B. C., Ryan, U. S., Michael, J. R., & Hoidal, J. R. (1992) · Journal of Clinical Investigation · doi:10.1172/jci115563 · Cited by 136
Xanthine oxidase activity in the circulation of rats following hemorrhagic shock
Tan, S., Yokoyama, Y., Dickens, E., Cash, T., Freeman, B. Α., & Parks, D. A. (1993) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(93)90040-2 · Cited by 134
[78] Oxygen-derived free radicals in reperfusion injury
Sussman, M. S., & Bulkley, G. B. (1990) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(90)86170-z · Cited by 122
Distribution of xanthine dehydrogenase and oxidase activities in human and rabbit tissues
Wajner, M., & HARKNESS, R. A. (1989) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/0304-4165(89)90031-7 · Cited by 115
THE URIC ACID CONTENT OF MATERNAL AND FETAL BLOOD
Slemons, J. M., & Bogert, L. J. (1917) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)86658-3 · Cited by 104
Chesley, L. C., & Williams, L. O. (1945) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(45)90138-4 · Cited by 95
Boyle, J. A., Campbell, S. C., Duncan, A. M., Greig, W. R., & Buchanan, W. W. (1966) · Journal of Clinical Pathology · doi:10.1136/jcp.19.5.501 · Cited by 93
Hassoun, P. M., Yu, F., Shedd, A. L., Zulueta, J. J., Thannickal, V. J., Lanzillo, J. J., & Fanburg, B. L. (1994) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.1994.266.2.l163 · Cited by 86
Uotila, J. T., Kirkkola, A.-L., Rorarius, M. G. F., Tuimala, R. J., & Metsä‐Ketelä, T. (1994) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(94)90058-2 · Cited by 84
Effect of allopurinol in renal ischemia.
Vasko, K. A., DeWall, R. A., & Am, R. (1972) · PubMed · Cited by 80
MacKenzie, I. Z. (1974) · The Lancet · doi:10.1016/s0140-6736(74)91719-x · Cited by 77
Purine and pyrimidine metabolism in man
Peters, G. J., ABREU, R. A. D., Gennip, A. H., Belle, H. V., & den Berghe, G. V. (1993) · Pharmacy World & Science · doi:10.1007/bf02297668 · Cited by 76
Super oxide and ischemia : Conversion of xanthine dehydrogenase to xanthine oxidase
Roy, R. (1983) · Medical Entomology and Zoology · Cited by 72
Role of xanthine oxidase and reactive oxygen intermediates in LPS- and TNF-induced pulmonary edema.
Faggioni, R., Gatti, S., Demitri, M. T., Delgado, R., Echtenacher, B., Gnocchi, P., Heremans, H., & Ghezzi, P. (1994) · PubMed · Cited by 66
O’Connor, M. C., HARKNESS, R. A., Simmonds, R. J., & Hytten, F. E. (1981) · BJOG An International Journal of Obstetrics & Gynaecology · doi:10.1111/j.1471-0528.1981.tb01001.x · Cited by 65
Endothelial cell activation as a pathogenetic factor in preeclampsia.
Roberts, J. M., Taylor, R. N., & Goldfien, A. (1991) · PubMed · Cited by 58
Self-citationUric acid and endogenous creatinine clearance studies in normal pregnancy and toxemias of pregnancy
Hayashi, T. T. (1956) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(56)90582-8 · Cited by 55
Interferons induce xanthine dehydrogenase gene expression in L929 cells
Francesco Falciani, B., Ghezzi, P., Terao, M., Cazzaniga, G., & Garattini, E. (1992) · Biochemical Journal · doi:10.1042/bj2851001 · Cited by 54
Role of oxygen radicals in tourniquet-related ischemia-reperfusion injury of human patients
Friedl, H. P., Till, G. O., Trentz, O., & Ward, P. A. (1991) · Journal of Molecular Medicine · doi:10.1007/bf01645168 · Cited by 53
High levels of xanthine oxidoreductase in rat endothelial, epithelial and connective tissue cells
Kooij, A., Bosch, K. S., Frederiks, W. M., & Noorden, C. J. F. V. (1992) · Virchows Archiv B Cell Pathology Including Molecular Pathology · doi:10.1007/bf02899676 · Cited by 51
Selective effects of preeclamptic sera on human endothelial cell procoagulant protein expression
Taylor, R. N., Casal, D., Jones, L. A., Varma, M., Martin, J. N., Jr., & Roberts, J. M. (1991) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(91)90019-n · Cited by 47
Self-citationTHE VALUE OF BLOOD URIC ACID LEVELS IN TOXAEMIA OF PREGNANCY
Lancet, M., & Fisher, I. L. (1956) · BJOG An International Journal of Obstetrics & Gynaecology · doi:10.1111/j.1471-0528.1956.tb05447.x · Cited by 46
Localisation of xanthine oxidase to synovial endothelium.
Stevens, C. R., Benboubetra, M., Harrison, R., Sahinoglu, T., Smith, E., & Blake, D. R. (1991) · Annals of the Rheumatic Diseases · doi:10.1136/ard.50.11.760 · Cited by 42
CORD PLASMA HYPOXANTHINE AS A MEASURE OF FOETAL ASPHYXIA
Thiringer, K. (1983) · Acta Paediatrica · doi:10.1111/j.1651-2227.1983.tb09703.x · Cited by 42
Hyperuricemia in pre-eclampsia
Fadel, H. E., Northrop, G., & Misenhimer, H. R. (1976) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(76)90786-9 · Cited by 40
Hällgren, R., Niklasson, F., Terént, A., Akerblom, A., & Widerlöv, E. (1983) · Stroke · doi:10.1161/01.str.14.3.382 · Cited by 39
Hypoxanthine: a marker for asphyxia.
Pietz, J., Guttenberg, N. A., & Gluck, L. (1988) · PubMed · Cited by 37
CLINICAL RELEVANCE OF COAGULATION AND RENAL CHANGES IN PRE-ECLAMPSIA
Dunlop, W., Landon, M. J., Hill, L. M., Oxley, A., & Jones, P. M. (1978) · The Lancet · doi:10.1016/s0140-6736(78)92944-6 · Cited by 35
Liedholm, H., Montán, S., & Åberg, A. (1984) · Acta Obstetricia Et Gynecologica Scandinavica · doi:10.3109/00016348409157122 · Cited by 32
Metabolism of uric acid in normal and toxemic pregnancy.
Lm, H. (1978) · PubMed · Cited by 29
Gallery, E. D. M., & Gyory, A. Z. (1979) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/0028-2243(79)90039-x · Cited by 28
AN EVALUATION OF THE SERUM URIC ACID LEVEL IN PREGNANCY
McFarlane, C. N. (1963) · BJOG An International Journal of Obstetrics & Gynaecology · doi:10.1111/j.1471-0528.1963.tb04180.x · Cited by 28
O’Connor, M. C., HARKNESS, R. A., Simmonds, R. J., & Hytten, F. E. (1981) · BJOG An International Journal of Obstetrics & Gynaecology · doi:10.1111/j.1471-0528.1981.tb01000.x · Cited by 25
Metabolism of Uric Acid in Normal and Toxemic Pregnancy
Hill, L. M. (1979) · Obstetrical & Gynecological Survey · doi:10.1097/00006254-197907010-00008 · Cited by 23
Metabolism of Uric Acid in Normal and Pathologic Pregnancy
Beaufils, M., Uzan, S., Donsimoni, R., Brault, D., & Colau, J. C. (2015) · Contributions to nephrology · doi:10.1159/000396023 · Cited by 23
Maguire, M. H., Szabó, I., Slégel, P., & King, C. R. (1992) · Journal of Chromatography B Biomedical Sciences and Applications · doi:10.1016/0378-4347(92)80152-g · Cited by 22
Maguire, M. H., Westermeyer, F. A., & King, C. R. (1986) · Journal of Chromatography B Biomedical Sciences and Applications · doi:10.1016/s0378-4347(00)83624-5 · Cited by 21
The Metabolism of Urate in Pre-Eclampsia
SEITCHIK, J. N. (1956) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(16)37509-3 · Cited by 21
Purine nucleotide catabolism in placenta
Hayashi, T. T., Baldridge, R. C., Olmsted, P. S., & Kimmel, D. L. (1964) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(64)90504-6 · Cited by 19
Tubulointerstitial Diseases of the Kidney
Truong, L. D., & Eknoyan, G. (1998) · Pathology Case Reviews · doi:10.1097/00132583-199807000-00004 · Cited by 19
Transplacental passage of nucleotides, nucleosides, and bases
Hayashi, T. T., & Garvey, B. I. (1968) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(68)90406-7 · Cited by 16
Serum uric acid in pre-eclampsia and eclampsia.
Fadel, H. E., Ms, S., Mahran, M., el-Din, D. S., & el-Mahallawi, M. N. (1969) · PubMed · Cited by 14
Significance of uric acid clearance in preeciampsia
Yoshimura, A., Ideura, T., Iwasaki, S., & Koshikawa, S. (1990) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(90)90953-5 · Cited by 11
Research works printed but not linked: 1
- Uotila, 1992, Plasma peroxyl radical tapping capacity in severe preeclamspia is strongly related to uric acid, Clin Exp Hypertens Pregnancy, B11-71
Cited by
Sorted by citations
Is There a Pathogenetic Role for Uric Acid in Hypertension and Cardiovascular and Renal Disease?
Johnson, R. J., Kang, D., Feig, D. I., Kivlighn, S. D., Kanellis, J., Watanabe, S., Tuttle, K. R., Rodríguez‐Iturbe, B., Herrera-Acosta, J., & Mazzali, M. (2003) · Hypertension · doi:10.1161/01.hyp.0000069700.62727.c5 · Cited by 1,354
Etiology and pathogenesis of preeclampsia: Current concepts
Dekker, G., & Sibai, B. M. (1998) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(98)70160-7 · Cited by 760
Oxidative Stress in the Pathogenesis of Preeclampsia
Hubel, C. A. (1999) · Proceedings of The Society for Experimental Biology and Medicine · doi:10.1046/j.1525-1373.1999.d01-139.x · Cited by 681
Self-citationBurton, G. J., Yung, H.-W., Cindrova-Davies, T., & Charnock-Jones, D. S. (2009) · Placenta · doi:10.1016/j.placenta.2008.11.003 · Cited by 502
Endothelial dysfunction and preeclampsia: role of oxidative stress
Sanchez-Aranguren, L. C., Prada, C. E., Riaño-Medina, C. E., & López, M. (2014) · Frontiers in Physiology · doi:10.3389/fphys.2014.00372 · Cited by 446
Metadata
- Authors
- Many, A., Hubel, C. A., & Roberts, J. M.
- Affiliations
- Magee-Womens Research Institute (US)
- Venue
- American Journal of Obstetrics and Gynecology
- Publisher
- Elsevier BV
- Published
- 1996-01
- Volume
- 174
- Issue
- 1
- Pages
- 288-291
- ISSN
- 0002-9378 (ISSN-L)
- OpenAlex
- W2139903790
- Cited by
- 187
- References
- 63
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 4 · 2022: 8 · 2021: 2 · 2020: 4 · 2019: 2 · 2018: 7 · 2017: 6 · 2016: 8 · 2015: 8 · 2014: 16 · 2013: 6 · 2012: 8
- FWCI
- 2.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Obstetrics and Gynecology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P01HD030367, 1 PO1 HD 30367-01, 1 PO1 HD 30367-02)
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Health Sciences › Medicine › Nephrology › Gout, Hyperuricemia, Uric Acid
- Health Sciences › Medicine › Clinical Neurology › Neurological Complications and Syndromes
- Keywords
- hyperuricemia, xanthine oxidase, xanthine dehydrogenase, preeclampsia, oxidative stress, reactive oxygen species, uric acid formation, trophoblast, maternal-fetal interface, hypoxia-reperfusion, cytokines, implantation depth, fetal outcomes
- MeSH terms
- Female, Humans, Kidney, Pre-Eclampsia, Pregnancy, Uric Acid, Xanthine Dehydrogenase, Xanthine Oxidase
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
