{"id":"https://openalex.org/W2122733445","doi":"https://doi.org/10.1097/01.asn.0000077405.07888.07","title":"Oxidative Stress","display_name":"Oxidative Stress","publication_year":2003,"publication_date":"2003-08-01","ids":{"openalex":"https://openalex.org/W2122733445","doi":"https://doi.org/10.1097/01.asn.0000077405.07888.07","mag":"2122733445","pmid":"https://pubmed.ncbi.nlm.nih.gov/12874434"},"language":"en","primary_location":{"id":"doi:10.1097/01.asn.0000077405.07888.07","doi":"https://doi.org/10.1097/01.asn.0000077405.07888.07","is_oa":false,"landing_page_url":"https://doi.org/10.1097/01.asn.0000077405.07888.07","pdf_url":null,"source":{"id":"https://openalex.org/S115693375","display_name":"Journal of the American Society of Nephrology","issn_l":"1046-6673","issn":["1046-6673","1533-3450"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310315620","host_organization_name":"American Society of Nephrology","host_organization_lineage":["https://openalex.org/P4310315620"],"host_organization_lineage_names":["American Society of Nephrology"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of the American Society of Nephrology","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5013630779","display_name":"Tatsuya Kuroki","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1293231726","display_name":"Joslin Diabetes Center","ror":"https://ror.org/0280a3n32","country_code":"US","type":"facility","lineage":["https://openalex.org/I1293231726"]},{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Tatsuya Kuroki","raw_affiliation_strings":["Vascular Cell Biology and Complications, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA","Vascular Cell Biology and Complications, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Vascular Cell Biology and Complications, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA","institution_ids":["https://openalex.org/I1293231726","https://openalex.org/I136199984"]},{"raw_affiliation_string":"Vascular Cell Biology and Complications, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts","institution_ids":["https://openalex.org/I1293231726","https://openalex.org/I136199984"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5012723015","display_name":"Keiji Isshiki","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1293231726","display_name":"Joslin Diabetes Center","ror":"https://ror.org/0280a3n32","country_code":"US","type":"facility","lineage":["https://openalex.org/I1293231726"]},{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Keiji Isshiki","raw_affiliation_strings":["Vascular Cell Biology and Complications, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Vascular Cell Biology and Complications, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts","institution_ids":["https://openalex.org/I1293231726","https://openalex.org/I136199984"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5009528569","display_name":"George Liang King","orcid":"https://orcid.org/0000-0002-0335-5881","observed_orcids":["https://orcid.org/0000-0002-0335-5881"]},"institutions":[{"id":"https://openalex.org/I1293231726","display_name":"Joslin Diabetes Center","ror":"https://ror.org/0280a3n32","country_code":"US","type":"facility","lineage":["https://openalex.org/I1293231726"]},{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"George L. King","raw_affiliation_strings":["Vascular Cell Biology and Complications, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts","to Dr. George L. King, Vascular Cell Biology and Complications, Joslin Diabetes Center, Harvard Medical School, One Joslin Place, Boston, MA 02215. Phone: 617-732-2660; Fax: 617-732-2637; E-mail: [email\u00a0protected]","E-mail: [email\u00a0protected]","Fax: 617-732-2637","to Dr. George L. King, Vascular Cell Biology and Complications, Joslin Diabetes Center, Harvard Medical School, One Joslin Place, Boston, MA 02215. Phone: 617-732-2660"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Vascular Cell Biology and Complications, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts","institution_ids":["https://openalex.org/I1293231726","https://openalex.org/I136199984"]},{"raw_affiliation_string":"to Dr. George L. King, Vascular Cell Biology and Complications, Joslin Diabetes Center, Harvard Medical School, One Joslin Place, Boston, MA 02215. Phone: 617-732-2660; Fax: 617-732-2637; E-mail: [email\u00a0protected]","institution_ids":["https://openalex.org/I1293231726","https://openalex.org/I136199984"]},{"raw_affiliation_string":"E-mail: [email\u00a0protected]","institution_ids":[]},{"raw_affiliation_string":"Fax: 617-732-2637","institution_ids":[]},{"raw_affiliation_string":"to Dr. George L. King, Vascular Cell Biology and Complications, Joslin Diabetes Center, Harvard Medical School, One Joslin Place, Boston, MA 02215. Phone: 617-732-2660","institution_ids":["https://openalex.org/I1293231726","https://openalex.org/I136199984"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5009528569"],"corresponding_institution_ids":["https://openalex.org/I1293231726","https://openalex.org/I136199984"],"apc_list":null,"apc_paid":null,"fwci":3.4643,"has_fulltext":false,"cited_by_count":91,"citation_normalized_percentile":{"value":0.92479596,"is_in_top_1_percent":false,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":88,"max":99},"biblio":{"volume":"14","issue":"suppl_3","first_page":"S216","last_page":"S220"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10155","display_name":"Nitric Oxide and Endothelin Effects","score":0.7401999831199646,"subfield":{"id":"https://openalex.org/subfields/2737","display_name":"Physiology (medical)"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10155","display_name":"Nitric Oxide and Endothelin Effects","score":0.7401999831199646,"subfield":{"id":"https://openalex.org/subfields/2737","display_name":"Physiology (medical)"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10445","display_name":"Antioxidant Activity and Oxidative Stress","score":0.18490000069141388,"subfield":{"id":"https://openalex.org/subfields/2704","display_name":"Biochemistry (medical)"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11142","display_name":"Advanced Glycation End Products research","score":0.03790000081062317,"subfield":{"id":"https://openalex.org/subfields/1308","display_name":"Clinical Biochemistry"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/oxidative-stress","display_name":"oxidative stress","score":0.9980000257492065},{"id":"https://openalex.org/keywords/diabetes-mellitus","display_name":"diabetes mellitus","score":0.8600000143051147},{"id":"https://openalex.org/keywords/insulin-resistance","display_name":"insulin resistance","score":0.9990000128746033},{"id":"https://openalex.org/keywords/hyperglycemia","display_name":"hyperglycemia","score":0.9700000286102295},{"id":"https://openalex.org/keywords/vascular-complications","display_name":"vascular complications","score":0.5170000195503235},{"id":"https://openalex.org/keywords/diabetic-microvascular-disease","display_name":"diabetic microangiopathy","score":0.7590000033378601},{"id":"https://openalex.org/keywords/cardiovascular-complications","display_name":"cardiovascular complications","score":0.7049999833106995},{"id":"https://openalex.org/keywords/oxidant-production","display_name":"oxidant production","score":0.5979999899864197},{"id":"https://openalex.org/keywords/free-fatty-acids","display_name":"free fatty acids","score":0.6480000019073486},{"id":"https://openalex.org/keywords/dyslipidemia","display_name":"dyslipidemia","score":0.7670000195503235},{"id":"https://openalex.org/keywords/antioxidants","display_name":"antioxidants","score":0.5389999747276306},{"id":"https://openalex.org/keywords/3-nitrotyrosine","display_name":"nitrotyrosine","score":0.7940000295639038},{"id":"https://openalex.org/keywords/oxidized-ldl","display_name":"oxidized LDL","score":0.8190000057220459},{"id":"https://openalex.org/keywords/isoprostanes","display_name":"isoprostanes","score":0.8579999804496765},{"id":"https://openalex.org/keywords/lipid-peroxidation","display_name":"lipid peroxidation","score":0.7829999923706055},{"id":"https://openalex.org/keywords/superoxide-radicals","display_name":"superoxide","score":0.49900001287460327},{"id":"https://openalex.org/keywords/insulin-secretion","display_name":"insulin secretion","score":0.4699999988079071},{"id":"https://openalex.org/keywords/glycemic-control","display_name":"glycemic control","score":0.6019999980926514},{"id":"https://openalex.org/keywords/oxidative-stress-biomarkers","display_name":"oxidative stress biomarkers","score":0.4129999876022339}],"concepts":[{"id":"https://openalex.org/C2776151105","wikidata":"https://www.wikidata.org/wiki/Q898814","display_name":"Oxidative stress","level":2,"score":0.8527534008026123},{"id":"https://openalex.org/C555293320","wikidata":"https://www.wikidata.org/wiki/Q12206","display_name":"Diabetes mellitus","level":2,"score":0.7943252325057983},{"id":"https://openalex.org/C134018914","wikidata":"https://www.wikidata.org/wiki/Q162606","display_name":"Endocrinology","level":1,"score":0.6826780438423157},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.6791190505027771},{"id":"https://openalex.org/C2778096610","wikidata":"https://www.wikidata.org/wiki/Q1476525","display_name":"Dyslipidemia","level":3,"score":0.6708323955535889},{"id":"https://openalex.org/C2777391703","wikidata":"https://www.wikidata.org/wiki/Q1053470","display_name":"Insulin resistance","level":3,"score":0.6181985139846802},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.6056578159332275},{"id":"https://openalex.org/C2779306644","wikidata":"https://www.wikidata.org/wiki/Q2002370","display_name":"Insulin","level":2,"score":0.5914208889007568},{"id":"https://openalex.org/C2780473172","wikidata":"https://www.wikidata.org/wiki/Q5572518","display_name":"Glycemic","level":3,"score":0.5752485394477844},{"id":"https://openalex.org/C2780942790","wikidata":"https://www.wikidata.org/wiki/Q372016","display_name":"Pathogenesis","level":2,"score":0.42622315883636475}],"mesh":[{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000975","descriptor_name":"Antioxidants","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":false},{"descriptor_ui":"D001205","descriptor_name":"Ascorbic Acid","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":false},{"descriptor_ui":"D003920","descriptor_name":"Diabetes Mellitus","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":false},{"descriptor_ui":"D003920","descriptor_name":"Diabetes Mellitus","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D014810","descriptor_name":"Vitamin E","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":false},{"descriptor_ui":"D018384","descriptor_name":"Oxidative Stress","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D048909","descriptor_name":"Diabetes Complications","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true}],"locations_count":2,"locations":[{"id":"doi:10.1097/01.asn.0000077405.07888.07","doi":"https://doi.org/10.1097/01.asn.0000077405.07888.07","is_oa":false,"landing_page_url":"https://doi.org/10.1097/01.asn.0000077405.07888.07","pdf_url":null,"source":{"id":"https://openalex.org/S115693375","display_name":"Journal of the American Society of Nephrology","issn_l":"1046-6673","issn":["1046-6673","1533-3450"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310315620","host_organization_name":"American Society of Nephrology","host_organization_lineage":["https://openalex.org/P4310315620"],"host_organization_lineage_names":["American Society of Nephrology"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of the American Society of Nephrology","raw_type":"journal-article"},{"id":"pmid:12874434","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/12874434","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of the American Society of Nephrology : JASN","raw_type":"Journal Article"}],"best_oa_location":null,"sustainable_development_goals":[{"display_name":"Good health and well-being","score":0.98580002784729,"id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[{"id":"https://openalex.org/G196759250","display_name":null,"funder_award_id":"NEY05110","funder_id":"https://openalex.org/F4320337350","funder_display_name":"National Eye Institute"},{"id":"https://openalex.org/G2029774737","display_name":"ENDOTHELIN EFFECTS ON RETINAL CELLS AND BLOOD FLOW","funder_award_id":"R01EY009178","funder_id":"https://openalex.org/F4320337350","funder_display_name":"National Eye Institute"},{"id":"https://openalex.org/G4609448951","display_name":null,"funder_award_id":"EY9178","funder_id":"https://openalex.org/F4320337350","funder_display_name":"National Eye Institute"}],"funders":[{"id":"https://openalex.org/F4320337350","display_name":"National Eye Institute","ror":"https://ror.org/03wkg3b53"}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":57,"referenced_works":["https://openalex.org/W83982660","https://openalex.org/W110780456","https://openalex.org/W1730700156","https://openalex.org/W1810991871","https://openalex.org/W1889397447","https://openalex.org/W1927620573","https://openalex.org/W1964094408","https://openalex.org/W1965845739","https://openalex.org/W1966423289","https://openalex.org/W1967527336","https://openalex.org/W1979356762","https://openalex.org/W1984313459","https://openalex.org/W1990868483","https://openalex.org/W1992313261","https://openalex.org/W1998707239","https://openalex.org/W2002680144","https://openalex.org/W2013529909","https://openalex.org/W2017202031","https://openalex.org/W2017612549","https://openalex.org/W2019358675","https://openalex.org/W2021491454","https://openalex.org/W2021976026","https://openalex.org/W2027478328","https://openalex.org/W2040923416","https://openalex.org/W2043828707","https://openalex.org/W2044432372","https://openalex.org/W2044437167","https://openalex.org/W2052730040","https://openalex.org/W2052931215","https://openalex.org/W2056216652","https://openalex.org/W2057051427","https://openalex.org/W2059467226","https://openalex.org/W2061712054","https://openalex.org/W2062548885","https://openalex.org/W2067184340","https://openalex.org/W2075578721","https://openalex.org/W2079230681","https://openalex.org/W2083990676","https://openalex.org/W2084420923","https://openalex.org/W2086501877","https://openalex.org/W2090736145","https://openalex.org/W2093441969","https://openalex.org/W2100738935","https://openalex.org/W2102617416","https://openalex.org/W2103783819","https://openalex.org/W2108462699","https://openalex.org/W2109168147","https://openalex.org/W2115766950","https://openalex.org/W2117692592","https://openalex.org/W2120329951","https://openalex.org/W2124098523","https://openalex.org/W2128728937","https://openalex.org/W2134924827","https://openalex.org/W2137348715","https://openalex.org/W2155931459","https://openalex.org/W2167513859","https://openalex.org/W2420170690"],"related_works":["https://openalex.org/W2007370526","https://openalex.org/W107323290","https://openalex.org/W2043060401","https://openalex.org/W2013529909","https://openalex.org/W4379914276","https://openalex.org/W1976422365","https://openalex.org/W135382720","https://openalex.org/W7096497214","https://openalex.org/W1994201341","https://openalex.org/W2951650934"],"abstract_inverted_index":{"Oxidative":[0],"stress":[1,32,49,126,152,213,303,738,773,788,824,873,1019,1248,1263,1348,1665,1810,1837,1849,1880,1936],"is":[2,50,162,199,556,562,578,583,597,603,623,641,732,746,766,778,819,869,935,1013,1020,1104,1180,1818,1833,1920],"increased":[3,96,153,215,291,358,1820],"in":[4,47,71,81,97,107,127,154,169,179,185,216,241,273,277,292,328,341,370,374,403,539,625,660,669,676,681,697,703,706,739,752,774,786,796,802,808,828,847,886,921,930,943,1051,1054,1065,1115,1202,1206,1221,1241,1267,1327,1361,1412,1424,1439,1449,1472,1504,1528,1542,1623,1644,1646,1667,1704,1719,1744,1749,1774,1796,1857,1867,1878,1887,1899,1916,1942],"both":[5,24,310,626,803,854],"diabetic":[6,113,131,155,192,274,343,627,708,743,829,840,887,914,1035,1052,1087,1158,1207,1268,1280,1333,1380,1435,1473,1505,1532,1562,1593,1812,1845,1914,1943,1957],"and":[7,11,19,42,62,76,80,106,114,133,156,208,225,230,258,267,276,312,331,352,361,376,387,398,418,447,463,481,520,628,646,663,683,709,725,759,805,834,842,856,929,964,976,984,1000,1003,1037,1053,1073,1093,1109,1113,1122,1124,1135,1147,1212,1216,1258,1284,1306,1318,1329,1350,1356,1364,1389,1405,1429,1438,1456,1493,1573,1637,1671,1678,1689,1713,1754,1766,1924,1970],"insulin":[8,40,353,396,806,1871],"resistance":[9,354,807,1872],"states":[10,344,356,671,711],"may":[12,1153,1196,1320,1457,1588,1627,1685,1793,1838,1850,1947],"contribute":[13],"to":[14,36,53,101,121,165,221,247,338,408,606,821,907,937,989,1015,1029,1043,1059,1106,1130,1138,1156,1166,1191,1291,1345,1378,1410,1451,1549,1619,1630,1883,1896],"the":[15,54,122,128,146,167,173,180,195,242,322,325,329,342,362,380,393,428,486,499,529,540,557,637,693,698,707,715,734,740,748,769,794,825,863,881,898,911,941,1069,1139,1183,1357,1362,1385,1425,1480,1516,1529,1543,1556,1590,1668,1681,1803,1806,1822,1840,1858,1890,1980],"development":[16],"of":[17,25,39,90,104,124,130,145,202,211,264,301,318,324,357,364,382,384,395,427,445,449,465,488,494,501,507,531,544,559,567,620,639,695,717,736,742,755,771,839,900,913,927,940,951,970,1010,1034,1071,1086,1097,1118,1171,1185,1199,1227,1230,1246,1261,1279,1332,1370,1372,1375,1387,1419,1469,1491,1515,1531,1558,1566,1592,1616,1659,1699,1709,1771,1788,1808,1824,1844,1893,1902,1956,1966],"microvascular":[18,132,830,888,1533,1540,1745,1859],"cardiovascular":[20,109,134,797,1286,1535,1747,1797],"diseases":[21,1462,1536],"associated":[22,1358],"with":[23,232,279,485,932,1569,1721,1752,1769,1869,1953],"these":[26,454,1862],"syndromes":[27],"(1\u20134).":[28],"In":[29,137,234,320,491,652,687,947,1232,1608,1801],"addition,":[30,492,688,1609],"oxidative":[31,48,125,212,302,359,442,483,649,737,772,787,823,872,1018,1247,1262,1347,1664,1809,1836,1848,1879,1935],"has":[33,244,304,458,918,986,1421,1612],"been":[34,245,271,306,336,459,471,919,954,987,1049,1081,1128,1219,1289,1422,1476,1502,1565,1640],"suggested":[35],"cause":[37,498,1030],"abnormalities":[38,1170,1708],"secretion":[41],"actions":[43,1194,1201,1205],"(5,6).":[44],"The":[45,729,894,968,1368,1467],"increases":[46,168,402,659,702,785,1877],"probably":[51],"due":[52,407,1189],"abnormal":[55],"metabolic":[56,1169],"milieu":[57],"such":[58,437,504,720,972,994,1173,1249,1264,1443,1463,1662,1729],"as":[59,120,299,438,505,721,973,995,1174,1250,1265,1444,1464,1663,1730,1821],"hyperglycemia,":[60,385,401],"dyslipidemia,":[61],"elevated":[63,102,262,563,813],"free":[64],"fatty":[65],"acids":[66,1187],"(FFA),":[67],"which":[68,391,421,561,622,809,1626,1735],"commonly":[69],"occur":[70,433],"patients":[72,231,278,849,931,1720,1751,1868],"who":[73],"have":[74,270,285,333,470,526,656,953,1048,1080,1127,1218,1288,1313,1343,1458,1475,1501,1518,1564,1582,1639,1654],"diabetes":[75,177,280,351,375,804,928,1172,1724,1753],"less-than-perfect":[77],"glycemic":[78,1176,1204],"control":[79],"insulin-resistant":[82,115,157,377,629,670,710,848,1055],"state":[83],"(7\u201310).":[84],"There":[85],"are":[86,95,214,290,355,366,379,392,406,477,762,800,844,1063,1188,1382,1483,1603,1864,1928],"a":[87,200,315,592,877,1007,1101,1225,1599,1705,1854,1884,1939,1976],"great":[88,1008],"deal":[89,1009],"evidence":[91,295,348,782,1012,1585,1804,1906],"that":[92,204,287,350,473,528,550,581,658,768,784,799,871,1017,1151,1315,1520,1586,1656,1695,1782,1815,1835,1907],"oxidant":[93,151,249,288,371,404,585,634,704,1816],"productions":[94,289,405,487,635,861],"vascular":[98,182,218,226,236,541,677,923,1036,1072,1307,1359,1492],"cells":[99,219,313,332,542,1448,1673],"exposed":[100,220],"levels":[103,224,240,263,323,534,662,694,1028],"glucose":[105,223,239,431,533,722,1027,1621,1825],"various":[108,326],"tissues":[110,227,678,685],"derived":[111,478,1433],"from":[112,228,479,714,726,862,1434,1598,1979],"states.":[116],"However,":[117,523,817,1161,1726,1847,1904],"controversy":[118],"exists":[119,349],"role":[123,827,885,1807,1856,1941],"pathogenesis":[129,741],"complications":[135,1159,1381,1563,1660,1813,1860,1863,1915],"(11).":[136],"this":[138,495,753,944],"article,":[139],"we":[140,1693],"briefly":[141],"provide":[142,1910],"an":[143,598,1021,1613],"overview":[144],"following":[147],"questions:":[148],"(1)":[149],"Is":[150],"states?":[158],"(2)":[159],"What":[160],"mechanisms":[161,1369],"hyperglycemia":[163,582,673,811,855,1352],"using":[164,1224,1340,1574,1579],"produce":[166],"oxidants?":[170],"(3)":[171],"Are":[172],"oxidants":[174,365,424,476],"induced":[175,1353],"by":[176,434,564,587,892,1025,1963],"involved":[178],"specific":[181],"pathologies":[183,838,1530],"observed":[184,373,801,846],"clinical":[186,294,1553,1648,1918],"diabetes?":[187],"(4)":[188],"Can":[189],"antioxidants":[190,327,952,971,1047,1062,1894,1908,1927,1946],"ameliorate":[191],"complications?":[193],"For":[194,400,1336],"first":[196],"question,":[197],"there":[198],"wealth":[201],"reports":[203,284,655,1312],"many":[205,949,965,1031,1244,1274],"protein,":[206],"lipid,":[207],"DNA":[209],"markers":[210,1033,1096,1260,1278,1490,1658,1666],"cultured":[217,235,922],"high":[222,532,1026,1373,1511,1697],"animals":[229,275,1208,1269,1334,1436,1474,1506],"diabetes.":[233,1119,1231,1903],"cells,":[237,1625],"elevating":[238],"media":[243],"shown":[246,337,1129,1314,1519],"increase":[248,514,552,633,859,1620],"production":[250,363,586,705,1817],"including":[251,832,956,1296],"gluco-oxidants,":[252],"glycated":[253,419,521],"compounds,":[254],"oxidized":[255,1110],"LDL,":[256],"superoxidants,":[257],"nitrotyrosine":[259],"(7,12\u201315).":[260],"Similarly,":[261,1650],"isoprostanes,":[265,1254],"8-hydroxydeoxyguanosine,":[266],"lipid":[268,1251,1390],"peroxides":[269],"reported":[272,527,988,1082,1290,1344,1423,1503,1655,1694],"(14\u201317).":[281],"Although":[282,757],"numerous":[283,1222],"substantiated":[286],"diabetes,":[293,851,1874],"for":[296,610,614,793,1460,1930],"tissue":[297,776,779],"damage":[298,777],"results":[300,394,1079,1468],"not":[305,334,674,763,880,1604,1740,1851,1865],"clearly":[307,747,1819],"demonstrated":[308,657],"because":[309,601,636,836,1861],"plasma":[311,330,699,1255],"contain":[314],"large":[316,1600,1727,1917],"reserve":[317],"antioxidants.":[319],"fact,":[321,653],"consistently":[335],"be":[339,423,667,790,875,905,1154,1292,1628,1717,1794,1852,1897,1948],"decreased":[340],"(18\u201320).":[345],"Nevertheless,":[346],"substantial":[347],"stress,":[360],"significantly":[367],"increased.":[368],"Increases":[369],"production,":[372],"states,":[378,630],"products":[381],"metabolisms":[383,546],"FFA,":[386,621],"other":[388,524,1094,1168,1440,1453,1461,1954],"metabolites":[389,719],"(2,8\u201310),":[390],"deficiency":[397],"resistance.":[399],"multiple":[409,588,615,718,727,1046,1830],"processes.":[410],"Glucose":[411],"can":[412,422,432,535,551,632,666,691,712,858,904,1401,1716,1909],"undergo":[413],"nonenzymatic":[414],"reactions":[415],"forming":[416],"gluco-oxidants":[417],"products,":[420],"(20,21).":[425],"Metabolisms":[426],"excessive":[429],"intracellular":[430],"several":[435,1452,1647,1756],"processes":[436],"aldose":[439,517],"reductase,":[440],"mitochondrial":[441,461,482,545,648,864],"phosphorylation,":[443],"activation":[444,464,500,506,558,1355],"oxidases,":[446],"alteration":[448],"NADPH/NADP":[450],"ratios":[451],"(7,22\u201324).":[452],"Among":[453],"possibilities,":[455],"recent":[456,654],"focus":[457],"on":[460,643,733,1083,1555,1561,1805,1811,1913],"metabolism":[462,530,638,716,865,1828],"NADPH":[466,537,553],"oxidases":[467],"(7,24).":[468],"Suggestions":[469],"made":[472],"most":[474,749,1552,1651],"glucose-induced":[475,565],"glycolysis":[480],"phosphorylation":[484,650],"superoxide":[489,860,1102,1388],"(7).":[490],"byproducts":[493],"process":[496,1843],"will":[497,1523],"signaling":[502],"cascades":[503],"protein":[508],"kinase":[509,1404],"C":[510,975,1112,1121,1211,1215,1235,1317,1636,1677],"(PKC),":[511],"hexosamine":[512],"productions,":[513],"flux":[515],"via":[516,570,1829],"reductase":[518],"(AR),":[519],"products.":[522],"authors":[525],"activate":[536,1402],"oxidase":[538,554],"independent":[543],"(24).":[547,575],"One":[548],"mechanism":[549],"activity":[555],"PKC,":[560],"elevation":[566,619],"diacylglycerol":[568],"(DAG)":[569],"de":[571],"novo":[572],"synthesis":[573],"pathway":[574,1023],"Thus,":[576,701,867,1006,1178,1922],"it":[577,602,765,818,868,1152,1179,1587],"very":[579,791,1570],"likely":[580,767,1834],"increasing":[584,1253],"pathways":[589],"rather":[590],"than":[591,613],"single":[593],"dominant":[594],"route.":[595],"This":[596,745,916,1416,1959],"important":[599,750,792,1022],"distinction":[600],"much":[604],"simpler":[605],"design":[607],"therapeutic":[608],"agents":[609],"one":[611],"target":[612],"pathways.":[616,728,1831],"Besides":[617,1271,1384],"glucose,":[618],"present":[624,1898],"also":[631,680,1881],"FFA":[640,689,724,814,857,1827],"dependent":[642],"\u03b2-hydroxylation,":[644],"acetyl-CoA,":[645],"uncouple":[647],"(8\u201310,25,26).":[651],"malondialdehyde":[661,1256],"NF-kB":[664,1266],"expression":[665],"detected":[668],"without":[672,850,1873],"only":[675,1190,1870,1938,1950],"but":[679,879,1479],"muscle":[682,1447,1624],"adipose":[684],"(10,27).":[686],"infusion":[690],"reduce":[692],"glutathione":[696],"(27).":[700],"originate":[713],"or":[723,812,883,909,1067,1195,1236,1240,1276,1294,1324,1399,1432,1487,1510,1525,1534,1643,1746,1791,1826],"third":[730],"question":[731,751,896,917],"importance":[735,770],"complications.":[744,915,1495,1846,1958],"field":[754],"investigations.":[756],"clear":[758],"direct":[760],"answers":[761],"available,":[764],"causing":[775],"specific.":[780],"Clinical":[781,1546],"suggests":[783,1814],"could":[789,874],"acceleration":[795],"risks":[798],"either":[810,1238,1508],"exist":[815,1882],"(1,2).":[816],"difficult":[820],"assign":[822],"lead":[826,882],"complications,":[831,1944],"nephropathy":[833],"retinopathy,":[835,1090,1281],"classical":[837],"retina":[841,1328,1363,1544],"glomeruli":[843,1366],"rarely":[845],"even":[852,1285,1321,1875],"though":[853,1876],"(2,7,8,25).":[866],"possible":[870],"playing":[876,1853],"supportive":[878,1011,1780,1905],"initiation":[884],"diseases.":[889],"Therapeutic":[890],"Trials":[891],"Antioxidants":[893,1770],"last":[895],"raises":[897],"issue":[899],"whether":[901,1061,1182],"antioxidant":[902,1193,1470,1521,1632,1683],"treatments":[903,1560],"effective":[906,1064,1155],"prevent":[908,990,1322,1379,1524],"delay":[910,1526],"onset":[912,1070],"tested":[920],"cell,":[924],"animal":[925,1116,1228,1550,1900],"models":[926,1117,1229,1901],"diabetes(28\u201333).":[933],"It":[934,1832],"impossible":[936],"review":[938],"all":[939],"literature":[942],"brief":[945],"overview.":[946],"general,":[948,1233],"types":[950,1442],"studied,":[955],"vitamin":[957,959,1234,1337,1376,1392,1700,1783],"C,":[958],"E,":[960,977,1338,1393],"\u03b2-carotene,":[961],"lipoic":[962,978],"acids,":[963],"others":[966,985],"(28\u201337).":[967],"addition":[969],"vitamins":[974,1111,1316,1676],"acid,":[979,1100],"antioxidative":[980,1559],"enzymes,":[981],"taurine,":[982],"acetylcystein,":[983],"hyperglycemia-induced":[991],"biologic":[992],"changes":[993,1085,1326,1486,1527,1541],"cytokine":[996],"induction,":[997],"matrix":[998],"synthesis,":[999],"cellular":[1001,1259],"growth":[1002,1454],"turnover":[1004],"(36\u201342).":[1005],"available":[1014,1606],"suggest":[1016],"activated":[1024],"surrogate":[1032,1095,1489,1576],"neurologic":[1038,1074,1494],"pathologies.":[1039],"Animal":[1040],"Studies":[1041,1547,1578],"Similar":[1042,1548],"cell-cultured":[1044],"studies,":[1045,1551,1652,1728,1761],"studied":[1050],"animals,":[1056],"mostly":[1057,1477],"rodents,":[1058],"determine":[1060],"preventing":[1066],"delaying":[1068],"functions":[1075],"(2,26,28,30,33\u201335,37,38,40,41).":[1076],"Again,":[1077],"favorable":[1078],"early":[1084,1275,1485,1538,1575,1657],"nephropathy,":[1088,1282],"neuropathy,":[1089,1283],"endothelial":[1091,1303,1687],"dysfunction,":[1092],"atherosclerosis.":[1098],"\u03b1-Lipoic":[1099],"scavenger,":[1103],"needed":[1105,1929],"regenerate":[1107],"glutatheine":[1108],"E":[1114,1123,1213,1217,1237,1319,1377,1638,1679,1701,1784],"Vitamins":[1120,1210,1214,1635],"\u03b1-lipoic":[1125,1162,1186,1580,1610],"acid":[1126,1163,1581,1611],"improve":[1131,1589,1686],"nerve":[1132,1299],"conduction":[1133,1300],"velocity":[1134],"blood":[1136,1297,1711],"flow":[1137,1712],"peripheral":[1140,1330],"nerves,":[1141],"retinal":[1142,1710],"leukocyte":[1143],"adhesions,":[1144],"cataract":[1145],"formation,":[1146],"mesangial":[1148],"expansion,":[1149],"suggesting":[1150],"treat":[1157],"(33,38,40\u201344).":[1160],"was":[1164,1961],"able":[1165,1618],"normalize":[1167,1346],"improved":[1175],"control.":[1177],"unclear":[1181],"effects":[1184,1500,1557,1892,1912],"its":[1192,1200,1631],"mediate":[1197],"some":[1198],"improving":[1203],"(37).":[1209],"characterized":[1220],"studies":[1223,1339,1517,1554],"variety":[1226],"individually":[1239,1642],"combination":[1242,1645],"normalized":[1243,1718],"parameters":[1245,1349],"peroxidation,":[1252,1391],"(MDA),":[1257],"(28,33,38,40\u201345).":[1270],"biochemical":[1272],"changes,":[1273],"functional":[1277],"disease":[1287],"prevented":[1293],"reversed,":[1295],"flow,":[1298],"velocity,":[1301],"permeability,":[1302],"dysfunctions,":[1304],"albuminuria,":[1305],"contractility":[1308],"(40).":[1309],"A":[1310],"few":[1311,1514,1571],"late":[1323],"pathology":[1325],"nerves":[1331],"(28,42).":[1335],"supra-antioxidant":[1341],"doses":[1342,1374,1684,1698,1787],"inhibit":[1351],"DAG/PKC":[1354],"dysfunctions":[1360,1688],"renal":[1365,1427,1714],"(42,44).":[1367],"action":[1371],"unclear.":[1383],"neutralization":[1386],"especially":[1394],"d-\u03b1-tocopherol,":[1395],"at":[1396,1507,1680,1696,1785],"50":[1397],"\u03bcM":[1398],"higher":[1400,1786],"DAG":[1403,1407],"decrease":[1406,1411],"level,":[1408],"leading":[1409,1855],"PKC":[1413],"activities":[1414],"(42).":[1415],"unusual":[1417],"effect":[1418],"d-\u03b1-tocopherol":[1420],"retina,":[1426],"glomeruli,":[1428],"macrophages":[1430],"isolated":[1431],"(42,45)":[1437],"cell":[1441],"aortic":[1445],"smooth":[1446],"response":[1450],"factors":[1455],"implications":[1459],"atherosclerosis":[1465],"(46\u201349).":[1466],"treatment":[1471,1522,1955],"positive,":[1478],"end":[1481],"points":[1482],"usually":[1484],"potential":[1488],"No":[1496],"significant":[1497],"untoward":[1498],"side":[1499],"low":[1509],"doses.":[1512],"Very":[1513],"except":[1537],"nonproliferative":[1539],"(28).":[1545],"short":[1567],"duration,":[1568],"people,":[1572],"markers.":[1577],"provided":[1583,1779],"suggestive":[1584],"symptoms":[1591],"polyneuropathy,":[1594],"but,":[1595],"again,":[1596,1653],"data":[1597],"controlled":[1601],"study":[1602,1960],"yet":[1605],"(34,50).":[1607],"additional":[1614],"property":[1615],"being":[1617],"transport":[1622],"related":[1629],"properties":[1633],"(37,51).":[1634],"used":[1641,1736],"studies.":[1649,1932],"improved,":[1661],"plasma,":[1669],"urine,":[1670],"circulating":[1672],"(52).":[1674],"Functionally,":[1675],"usual":[1682],"microalbuminuria":[1690],"(43,53).":[1691],"Previously,":[1692],"(1800":[1702],"IU/d)":[1703],"placebo-controlled":[1706],"trial,":[1707],"hyperfiltration":[1715],"type":[1722],"1":[1723],"(33).":[1725],"Heart":[1731,1763],"Outcomes":[1732],"Prevention":[1733,1768],"Evaluation,":[1734],"400":[1737],"IU/d,":[1738],"did":[1739],"find":[1741],"any":[1742],"benefit":[1743],"events":[1748,1798],">3000":[1750],"after":[1755],"years":[1757],"(54).":[1758],"Two":[1759],"smaller":[1760],"Cambridge":[1762],"Antioxidant":[1764],"Study":[1765],"Secondary":[1767],"Cardiovascular":[1772],"Disease":[1773,1777],"End-Stage":[1775],"Renal":[1776],"(SPACE),":[1778],"evidences":[1781],"600":[1789],"mg/d":[1790],"greater":[1792],"helpful":[1795,1949],"(55,56).":[1799],"Summary":[1800],"summary,":[1802],"result":[1823],"accelerate":[1839],"basic":[1841],"pathogenic":[1842],"evident":[1866],"similar":[1885],"extent":[1886],"both.":[1888],"Conversely,":[1889],"beneficial":[1891,1911],"seem":[1895],"trials":[1919],"lacking.":[1921],"new":[1923],"more":[1925],"powerful":[1926],"future":[1931],"Alternatively,":[1933],"if":[1934],"plays":[1937],"supporting":[1940],"then":[1945],"when":[1951],"paired":[1952],"supported":[1962],"National":[1964],"Institutes":[1965],"Health":[1967],"Grants":[1968],"NEY05110":[1969],"EY9178.":[1971],"Dr.":[1972],"Keiji":[1973],"Isshiki":[1974],"received":[1975],"mentor":[1977],"fellowship":[1978],"American":[1981],"Diabetes":[1982],"Association.":[1983]},"counts_by_year":[{"year":2025,"cited_by_count":1},{"year":2024,"cited_by_count":2},{"year":2023,"cited_by_count":2},{"year":2022,"cited_by_count":1},{"year":2021,"cited_by_count":2},{"year":2020,"cited_by_count":2},{"year":2019,"cited_by_count":2},{"year":2018,"cited_by_count":1},{"year":2017,"cited_by_count":4},{"year":2016,"cited_by_count":3},{"year":2015,"cited_by_count":5},{"year":2014,"cited_by_count":1},{"year":2013,"cited_by_count":5},{"year":2012,"cited_by_count":13}],"updated_date":"2026-11-05T12:25:35.769452","created_date":"2016-06-24T00:00:00"}
