title: Effects of two oral antidiabetics, pioglitazone and repaglinide, on aconitase inactivation, inflammation and oxidative/nitrosative stress in tissues under alloxan-induced hyperglycemia.
abstract: Pathological changes identified in different tissues in hyperglycemic state are undoubtedly connected with increased oxidative/nitrosative stress and inflammation. In our study myeloperoxidase (MPO), nitrotyrosine and lipid peroxidation were enhanced in the heart and lung of alloxan-treated hyperglycemic animals. Additionally, pulmonary aconitase was inhibited. In the testis the changes occurred as an increase of MPO and lipid peroxidation, and as a decrease of aconitase. The effects of two different antidiabetics, the peroxisome proliferator activated receptor gamma (PPARγ) agonist, pioglitazone, and a short acting insulin secretagogue, repaglinide, on the mentioned parameters, were investigated and compared. The insulin deficient alloxan-induced hyperglycemic animals were used to differentiate a direct anti-oxidative effect of the drugs from secondary effects mediated via increased insulin sensitivity or secretion. Pioglitazone acted by normalization of pulmonary and testicular aconitase, normalization of pulmonary and cardiac nitrotyrosine, reduction of pulmonary and testicular MPO, and by reduction of lipid peroxidation in all tissues examined. Repaglinide prevented oxidative changes by normalization of aconitase activity in the lung and testis, and by reduction of lipid peroxidation and nitrotyrosine in the heart and lung. At the same time, no effect of this drug on MPO was observed. Finally, principal component analysis was performed to explore and visualize similarities and differences of the results obtained for the both drugs.
authors.forename: Anna
authors.initials: A
authors.lastname: Gumieniczek
authors.forename: Lukasz
authors.initials: L
authors.lastname: Komsta
authors.forename: Marita Rachid
authors.initials: MR
authors.lastname: Chehab
mesh_terms: D000154:Aconitate Hydratase / Q000378:metabolism*; D000284:Administration, Oral; D000496:Alloxan / Q000009:adverse effects*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002219:Carbamates / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004789:Enzyme Activation / Q000187:drug effects; D006943:Hyperglycemia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy; D007328:Insulin / Q000097:blood; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D000077205:Pioglitazone; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D011817:Rabbits; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D001786:Blood Glucose; D002219:Carbamates; D007004:Hypoglycemic Agents; D007328:Insulin; D010880:Piperidines; D026361:Reactive Nitrogen Species; D045162:Thiazolidinediones; C072379:repaglinide; D000496:Alloxan; D000154:Aconitate Hydratase; D000077205:Pioglitazone