title: The paraoxonase 1 (PON1), platelet-activating factor acetylohydrolase (PAF-AH) and dimethylarginine dimethylaminohydrolase (DDAH) activity in the metformin treated normal and diabetic rats.
abstract: Antidiabetic agents per se, apart from their glucose-lowering effect, can have an important impact on modifying the cardiovascular risk. The present study was undertaken to determine whether the known cardio-protective effects of metformin are linked to its potential ability to affect activities of HDL's paraoxonase (PON1) and platelet activating factor acetylohydrolase (PAF-AH) or via its interaction with the asymmetric dimethylarginine (ADMA)- dimethylarginine dimethylaminohydrolase (DDAH) axis. Normal and streptozotocin (STZ)-induced diabetic rats were treated with metformin (300mg/kg; 4 weeks). The activity of PON1, PAF-AH and DDAH were measured spectrophotometrically. The plasma ADMA level was determined by ELISA method. In STZ-induced diabetic rats the long-term administration of metformin normalized reduced PON1 activity assayed toward paraoxon (+42.5%, P<0.05), phenyl acetate (+22.35%, P<0.05) and γ-decanolactone (+108.0%, P<0.01), without affecting elevated PAF-AH activity in the plasma. Moreover, metformin increased DDAH activity in the renal cortex (+38.24%, P<0.01). Additionally metformin administration caused the increase in PON1 activity in the liver (+29.2%, P<0.01) accompanied by the reduction in the lipid peroxidation (-59.8%, P<0.001). Similarly, in non-diabetic treated rats the increase in liver PON1 activity was observed toward both paraoxon (+80.19%, P<0.001) and phenyl acetate (+29.3%, P<0.05), respectively. The present study has demonstrated that insulin-sensitizer metformin is important for preserving antioxidant HDL function in diabetes. Metformin might also exert its effect against diabetic complications by improving DDAH activity in the kidney and increasing PON1 activity in the liver.
authors.affiliation: Department of Pathophysiology, Medical University of Lublin, ul. Jaczewskiego 8b, 20-090 Lublin, Poland. Electronic address: grazyna.wojcicka@umlub.pl.
authors.forename: Grażyna
authors.initials: G
authors.lastname: Wójcicka
authors.affiliation: Department of Neurology, Medical University of Lublin, ul. Jaczewskiego 8, 20-090 Lublin, Poland. Electronic address: anna.jamroz@umlub.pl.
authors.forename: Anna
authors.initials: A
authors.lastname: Jamroz-Wiśniewska
authors.affiliation: Department of Pharmacology, Medical University of Lublin, ul. Chodźki 4a, 20-093 Lublin, Poland. Electronic address: grazyna.czechowska@umlub.pl.
authors.forename: Grażyna
authors.initials: G
authors.lastname: Czechowska
authors.affiliation: Department of Pathophysiology, Medical University of Lublin, ul. Jaczewskiego 8b, 20-090 Lublin, Poland. Electronic address: agnieszka.korolczuk@umlub.pl.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Korolczuk
authors.affiliation: Department of Pharmacology, Medical University of Lublin, ul. Chodźki 4a, 20-093 Lublin, Poland. Electronic address: sebastian.marciniak@umlub.pl.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Marciniak
authors.affiliation: Department of Pathophysiology, Medical University of Lublin, ul. Jaczewskiego 8b, 20-090 Lublin, Poland. Electronic address: jerzy.beltowski@umlub.pl.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Bełtowski
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000378:metabolism*; D000581:Amidohydrolases / Q000378:metabolism*; D000818:Animals; D043303:Aryldialkylphosphatase / Q000097:blood / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000201:enzymology* / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008687:Metformin / Q000494:pharmacology* / Q000627:therapeutic use; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014443:Tyrosine / Q000031:analogs & derivatives / Q000097:blood
chemical_list: D007004:Hypoglycemic Agents; C002744:3-nitrotyrosine; D014443:Tyrosine; D008687:Metformin; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D043303:Aryldialkylphosphatase; D000581:Amidohydrolases; C059999:dimethylargininase
keywords: Asymmetric dimethylarginine; Dimethylarginine dimethylaminohydrolase; Metformin; Paraoxonase 1; Platelet activating factor acetylohydrolase