High glucose concentrations abolish the superoxide dismutase response of leukocytes to ascorbic acid or troglitazone in type 2 diabetes mellitus.
The hypoglycemic drug, troglitazone (TGZ) has antioxidant activity. Superoxide dismutase (SOD) removes superoxide produced by cells. We measured the response of SOD-like activity (deltaSOD) to ascorbic acid (AA) or TGZ using electron spin resonance at various glucose concentrations in polymorphonuclear leukocytes from 18 type 2 diabetic patients and 18 healthy controls. In control and diabetic subjects, ASOD in response to AA was dose-dependent (maximal effect at 100 ng/ml). Maximal response occurred 2 min after AA addition (50 ng/ml). In cells from diabetic patients, ASOD with 25 ng/ml AA was significantly less than for healthy controls. The deltaSOD with AA changed little at glucose concentration from 0 to 200 mg/dl. In patient and control cells, higher glucose concentrations (400 to 800 mg/dl) reduced ASOD with AA. Response patterns with TGZ resembled those with AA. deltaSOD with AA correlated positively with glycosylated hemoglobin A1c.


CONCLUSIONS
The present data suggest that an amerioration of blood glucose on high levels in diabetic patients plays an important role in an antioxidant efficacy of TGZ and AA on leukocytes in patients.
Inukai
Toshihiko
T
Department of Medicine, Koshigaya Hospital, Dokkyo University School of Medicine, Saitama, Japan. t-inukai@dokkyomed.ac.jp
Takanashi
Keishi
K
Tayama
Kazumi
K
Aso
Yoshimasa
Y
Takemura
Yoshihiro
Y
D000368:Aged; D000419:Albuminuria / Q000209:etiology; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D002839:Chromans / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000201:enzymology*; D003928:Diabetic Nephropathies / Q000473:pathology; D003930:Diabetic Retinopathy / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004578:Electron Spin Resonance Spectroscopy; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007962:Leukocytes / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D013482:Superoxide Dismutase / Q000096:biosynthesis*; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D000077288:Troglitazone
D000975:Antioxidants; D001205:Ascorbic Acid; D002839:Chromans; D005947:Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D013482:Superoxide Dismutase; D013844:Thiazoles; D045162:Thiazolidinediones; D000077288:Troglitazone