{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T06:11:47Z","timestamp":1775801507536,"version":"3.50.1"},"reference-count":25,"publisher":"American Diabetes Association","issue":"7","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2005,7,1]]},"abstract":"<jats:p>OBJECTIVE\u2014Defective intracellular antioxidant enzyme production (IAP) has been demonstrated in adults with diabetic nephropathy. The objective of this study was to evaluate the effects of irbesartan, an angiotensin II receptor antagonist, on IAP in adolescents and young adults with type 1 diabetes and early signs of retinopathy and nephropathy.<\/jats:p>\n               <jats:p>RESEARCH DESIGN AND METHODS\u2014This prospective, matched case-control study was conducted between November 2001 and December 2002 among 14 type 1 diabetic patients with early signs of angiopathy (ages 14\u201321 years), 11 type 1 diabetic patients without angiopathy (ages 12\u201322 years), and 10 healthy volunteers (ages 16\u201322 years). Skin fibroblasts were obtained by skin biopsies from the anterior part of the forearm and cultured in Dulbecco\u2019s modified Eagle\u2019s medium. The activity and mRNA expression of CuZn superoxide dismutase (CuZnSOD), Mn superoxide dismutase (MnSOD), catalase (CAT), and glutathione peroxidase (GPX) were measured before and after 6 months of treatment with irbesartan (150 mg\/day); on both occasions, antioxidant enzyme activity was evaluated at different glucose concentrations (5 and 22 mmol\/l).<\/jats:p>\n               <jats:p>RESULTS\u2014At a normal glucose concentration (5 mmol\/l), the activity and mRNA expression of CuZnSOD (0.50 \u00b1 0.21 units\/mg protein, 4.4 \u00b1 1.5 mRNA\/glyceraldehyde-3-phosphate dehydrogenase), MnSOD (0.26 \u00b1 0.04 units\/mg protein, 0.08 \u00b1 0.07 mRNA), CAT (0.32 \u00b1 0.08 units\/mg protein, 4.8 \u00b1 1.3 mRNA), and GPX (0.53 \u00b1 0.09 units\/mg protein, 2.2 \u00b1 0.9 mRNA) were not different among the three groups (only values of diabetic subjects with angiopathy are shown). At high glucose concentrations, the activity and mRNA expression of CuZnSOD increased similarly in all groups (diabetic subjects with angiopathy: 0.93 \u00b1 0.26 units\/mg protein, 9.4 \u00b1 2.1 mRNA); that of CAT and GPX increased in only control subjects and diabetic subjects without angiopathy (diabetic subjects with angiopathy: 0.33 \u00b1 0.09 units\/mg protein and 5.0 \u00b1 1.4 mRNA; 0.54 \u00b1 0.10 units\/mg protein and 2.3 \u00b1 1.0 mRNA, respectively). MnSOD did not change in any group. Treatment with irbesartan in adolescents with diabetic angiopathy was able to restore CAT and GPX activity and mRNA expression after exposure to high glucose concentrations. Markers of oxidative stress (serum malondialdehyde, fluorescent products of lipid peroxidation, monocyte chemoattractant protein-1, and 8-isoprostanes prostaglandin F2\u03b1) were significantly reduced after treatment with irbesartan.<\/jats:p>\n               <jats:p>CONCLUSIONS\u2014Adolescents and young adults with early signs of diabetic angiopathy have defective intracellular antioxidant enzyme production and activity. Treatment with irbesartan can substantially improve the activity and production of these enzymes in skin fibroblasts.<\/jats:p>","DOI":"10.2337\/diacare.28.7.1690","type":"journal-article","created":{"date-parts":[[2007,3,5]],"date-time":"2007-03-05T22:51:27Z","timestamp":1173135087000},"page":"1690-1697","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":34,"title":["Effects of Irbesartan on Intracellular Antioxidant Enzyme Expression and Activity in Adolescents and Young Adults With Early Diabetic Angiopathy"],"prefix":"10.2337","volume":"28","author":[{"given":"Francesco","family":"Chiarelli","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Chieti, Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniele","family":"Di Marzio","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Chieti, Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Santilli","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Chieti, Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelika","family":"Mohn","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Chieti, Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annalisa","family":"Blasetti","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Chieti, Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Cipollone","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Chieti, Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Mezzetti","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Chieti, Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto","family":"Verrotti","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Chieti, Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1167","reference":[{"key":"2022031218301763400_R1","unstructured":"Ceriello A, Giugliano D: Oxidative stress and diabetic complications. 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