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Hydroxyethyl starch deferoxamine, a novel iron chelator, delays diabetes in BB rats. J Lab Clin Med 1994 Apr;123(4):556-60

Date

04/01/1994

Pubmed ID

7511676

Scopus ID

2-s2.0-0028406113   11 Citations

Abstract

Hydroxyl radicals (.OH) may contribute to beta cell death. Because iron catalyzes .OH production, we examined whether administration of a novel, long-acting iron chelator, hydroxyethyl starch-deferoxamine (HES-DFO) could prevent diabetes in spontaneously diabetic biobreeding (BB) rats. In our colony, a peripheral lymphocyte count (PBLC) < 4200 mm3 has an 88% positive predictive value for onset of diabetes mellitus (DM). Rats with PBLC < 4200 mm3 were randomized at 6 weeks of age to receive 50 mg/kg of HES-DFO (a high molecular weight hydroxyethyl starch-conjugated derivative of deferoxamine) or equimolar hydroxyethyl starch (HES) alone given intraperitoneally three times weekly until DM or 120 days of age. Administration of HES significantly decreased the incidence of IDDM to 57% as compared with the incidence of 87% in the lymphopenic unmanipulated BB rats in the colony (p < 0.01). Administration of HES-DFO further significantly decreased the incidence of IDDM to 31% as compared with the lymphopenic unmanipulated rats (p < 0.01). When analyzed by sex, 3 of 17 (18%) HES-DFO-treated males developed DM, versus 10 of 17 (58%) of HES-treated males (p < 0.05, chi square); 8 of 19 (42%) of HES-DFO-treated females developed DM, versus 11 of 20 (55%) HES-treated females (p = NS). There were no differences between the groups in (1) mean time of onset of DM, (2) serum iron levels at study entry and completion, (3) weekly hematocrits, (4) total lymphocyte counts; and (5) weekly weight gains.(ABSTRACT TRUNCATED AT 250 WORDS)

Author List

Roza AM, Slakey DP, Pieper GM, Van Ye TM, Moore-Hilton G, Komorowski RA, Johnson CP, Hedlund BE, Adams MB

Authors

Christopher P. Johnson MD Professor in the Surgery department at Medical College of Wisconsin
Allan M. Roza MD Professor in the Surgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Deferoxamine
Diabetes Mellitus, Type 1
Drug Administration Schedule
Female
Hematocrit
Hydroxyethyl Starch Derivatives
Iron
Leukocyte Count
Male
Predictive Value of Tests
Random Allocation
Rats
Rats, Inbred BB
jenkins-FCD Prod-478 d1509cf07a111124a2d122fd3df854cc0b993c00