title: The differentiating effect of glimepiride and glibenclamide on paraoxonase 1 and platelet-activating factor acetylohydrolase activity.
abstract: OBJECTIVE
  The present study was designed to examine the effect of sulphonylureas, glimepiride (GM) and glibenclamide (GB), on paraoxonase 1 (PON1) and platelet activating factor acetylohydrolase (PAF-AH) activity in normal and streptozotocin (STZ)-induced (50 mg/kg) diabetic rats.
  
  
  METHODS
  In treated groups, glimepiride (0.1 mg/kg) or glibenclamide (2 mg/kg) was given orally for 4 weeks. A PON1 and PAF-AH activity were estimated by spectrophotometric method.
  
  
  RESULTS
  Hyperglycemia was accompanied by a significant decrease in plasma PON1 activity toward paraoxon (P < 0.001) and phenyl acetate (P < 0.01) and increase in plasma PAF-AH activity (P < 0.01). In STZ-induced diabetic rats the administration of both GM and GB had no effect on plasma PON1 activity but reversed elevated plasma PAF-AH activity (GM: P < 0.05, GB: P < 0.01). In non-diabetic rats after either GM or GB administration the decreased PON1 activity in the plasma was observed (GM: P < 0.001, GB: P < 0.05), but plasma PAF-AH activity remained unchanged. Both GM and GB had no effect on total plasma antioxidant capacity in diabetic and control treated groups. Additionally, both drugs increased PON1 activity toward phenyl acetate in the liver, in diabetic rats (GM: P < 0.05, GB:ns) as well as in non-diabetic rats (GM: P < 0.001, GB: P < 0.001), and reduced lipid peroxidation in the liver.
  
  
  CONCLUSIONS
  These results demonstrate that in streptozotocin-induced diabetic rats as well as in normal rats glimepiride and glibenclamide have no beneficial effects on circulating PON1 and PAF-AH activities, but both drugs increase PON1 activity in the liver.
authors.affiliation: Department of Pathophysiology, Medical University, ul Jaczewskiego 8, 20-090 Lublin, Poland. grazyna.wojcicka@am.lublin.pl
authors.forename: Grazyna
authors.initials: G
authors.lastname: Wójcicka
authors.forename: Anna
authors.initials: A
authors.lastname: Jamroz-Wiśniewska
authors.forename: Andrzej
authors.initials: A
authors.lastname: Marciniak
authors.forename: Ewelina
authors.initials: E
authors.lastname: Łowicka
authors.forename: Jerzy
authors.initials: J
authors.lastname: Bełtowski
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D043303:Aryldialkylphosphatase / Q000187:drug effects* / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000201:enzymology; D005905:Glyburide / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013053:Spectrophotometry; D013311:Streptozocin; D013453:Sulfonylurea Compounds / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D013311:Streptozocin; C057619:glimepiride; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D043303:Aryldialkylphosphatase; D005905:Glyburide