Combination treatment of vitamin C and desferrioxamine suppresses glomerular superoxide and prostaglandin E production in diabetic rats.
OBJECTIVE
Increased oxidative stress may contribute to the development of diabetic nephropathy. Conversely, it has been proposed that enhanced glomerular production of prostaglandin E(2) (PGE(2)) may be the cause of glomerular hyperfiltration in streptozotocin (STZ)-induced diabetic rats. As the role of superoxide anion (O(2-)) production in early diabetic nephropathy is not fully understood, we investigated the effect of vitamin C and desferrioxamine treatment on glomerular O(2-) and PGE(2) production in diabetic rats.


METHODS
STZ-induced diabetic rats were given drinking water containing 1 g/l of vitamin C and desferrioxamine for 10 days, and glomerular O(2-) production, glomerular PGE(2) synthesis and creatinine clearance were examined.


RESULTS
Glomerular O(2-) production increased in untreated diabetic rats compared to non-diabetic controls (142.2 +/- 12.4 vs. 65.4 +/- 3.6 counts/mg protein/min). Treatment with vitamin C and desferrioxamine significantly decreased glomerular O(2-) production (93.7 +/- 6.7 counts/mg protein/min). Glomerular PGE(2) synthesis and creatinine clearance were significantly increased in untreated diabetic rats compared to controls and PGE(2) synthesis was reduced and creatinine clearance tended to decrease by the treatment.


CONCLUSIONS
Our results demonstrated that vitamin C and desferrioxamine suppressed the enhanced glomerular O(2-) production with subsequent decrease in PGE(2) production. Antioxidant therapy may be beneficial in preventing the development of diabetic nephropathy.
Iino
K
K
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyusyu University, Fukuoka 812-8582, Japan. iinok@jcom.home.ne.jp
Iwase
M
M
Sonoki
K
K
Yoshinari
M
M
Iida
M
M
D000818:Animals; D001205:Ascorbic Acid / Q000008:administration & dosage*; D003676:Deferoxamine / Q000008:administration & dosage*; D003864:Depression, Chemical; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism*; D015232:Dinoprostone / Q000096:biosynthesis*; D007502:Iron Chelating Agents / Q000008:administration & dosage*; D007678:Kidney Glomerulus / Q000378:metabolism*; D008163:Luminescent Measurements; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism*
D007502:Iron Chelating Agents; D013481:Superoxides; D003676:Deferoxamine; D015232:Dinoprostone; D001205:Ascorbic Acid