Protective effects of a PPARgamma agonist pioglitazone on anti-oxidative system in testis of diabetic rabbits.

In the present study, modulation of oxidative stress by pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARgamma) agonist, was examined in testis of alloxan-induced diabetic rabbits. In diabetic animals, an increase in the activity of anti-oxidative enzymes: superoxide dismutase (Cu,Zn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione reductase (GSSG-R), and in the level of glutathione (GSH) but a decrease in the level of ascorbic acid (AA) were observed. These effects were accompanied by a significant increase in testicular lipid and protein oxidation. Pioglitazone affected the activity of Cu,Zn-SOD, normalized the activity of CAT, the level of AA as well as the levels of LPO and PCG without having any significant effect on blood glucose level.

Interleukin-6 and oxidative stress in plasma of alloxan-induced diabetic rabbits after pioglitazone treatment.

There is evidence that oxidative stress might be implicated in promoting a state of systemic inflammation in diabetic patients. Understanding the role of reactive oxygen species in the inflammatory response in diabetes becomes essential in finding preventive treatments. Pioglitazone is a new oral antidiabetic agent with potent antioxidant and anti-inflammatory properties. The drug is a high affinity ligand of peroxisome proliferator-activated receptor gamma. This receptor seems to be involved in the control of inflammation by modulating the production of inflammatory mediators. In the present study, the changes in some markers of enhanced oxidative stress and in the level of pro-inflammatory interleukin-6 (IL-6) were examined in plasma of diabetic rabbits after 4 and 8 weeks of pioglitazone treatment. Ascorbic acid (AA) concentration and total antioxidant status (TAS) in plasma of diabetic animals were diminished and significantly elevated after pioglitazone treatment (p < 0.05). Protein carbonyl groups (PCG) content and IL-6 concentration were elevated in plasma of diabetic animals and significantly diminished after pioglitazone treatment. The results obtained in the present study confirm the relations of cytokine systems with oxidative stress in plasma of diabetic subjects. They also suggest the antioxidative and antinflammatory properties of pioglitazone.

Oxidative stress in kidney and liver of alloxan-induced diabetic rabbits: effect of repaglinide.

The aim of this study was to analyse the effect of the new oral antidiabetic drug repaglinide on antioxidant factors and lipid peroxidation in tissues of alloxan-induced diabetic rabbits after 4 and 8 weeks treatment. The activity of superoxide dismutase (diabetic vs. control values, mean+/-S.E.M., p<0.05) in diabetic kidney was diminished (1.5+/-0.2 vs. 2.8+/-0.3 and 1.8+/-0.1 vs. 2.9+/-0.3 U/mg protein) and significantly increased after 8 weeks of repaglinide treatment (2.4+/-0.2 U/mg protein). Catalase activity was significantly increased in diabetic liver (67.5+/-3.6 vs. 39.7+/-5.6 and 62.3+/-2.7 vs. 52.6+/-5.3 micromol H(2)O(2)/min/mg protein) and normalised by repaglinide (49.2+/-4.0 and 41.2+/-3.8 micromol H(2)O(2)/min/mg protein). In diabetic kidney the level of ascorbic acid was diminished after 4 weeks (1.5+/-0.1 vs. 3.0+/-0.1 micromol/g tissue) and increased after the drug treatment (2.0+/-0.2 micromol/g tissue). In diabetic kidney the level of lipid peroxidation products was elevated (33.3+/-2.4 vs. 23.7+/-2.4 and 29.5+/-3.1 vs. 18.2+/-0.8 nmol/g tissue) and diminished by repaglinide (10.3+/-1.4 and 13.3+/-3.0 nmol/g tissue). This study shows that oxidative stress in diabetic tissues is partly corrected by repaglinide. The drug does not affect glucose concentration and its antioxidative effect is not secondary to its action on hyperglycaemia. This study suggests an additional advantage of repaglinide which contributes to its effectiveness in therapy.

Differences in antioxidant status in skeletal muscle tissue in experimental diabetes.

BACKGROUND: It has been suggested that oxidative stress may play an important role in pathogenesis of diabetic complications. The present study was designed to evaluate the oxidative stress-related parameters in alloxan (A)-induced long-term diabetes in rabbits. METHODS: After 3, 6 and 12 weeks of diabetes, activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R) and concentrations of ascorbic acid (AA) and free sulfhydryl compounds (SH) were measured in skeletal muscle of diabetic rabbits and the normal control subjects. The products of lipid peroxidation (MDA) were also estimated. RESULTS: In our tests, the muscle SOD activity, SH and AA concentrations were significantly reduced. CAT activity increased significantly at all time intervals. GSH-Px activity decreased after 3 weeks and then remained at the control level. GSSG-R activity decreased progressively at 3rd and 6th week and then significantly increased. MDA level increased initially, dropped below baseline after 6 weeks and then remained at the level of the control group. CONCLUSIONS: The changes observed in the present experiment suggest a significant imbalance in antioxidative system in the skeletal muscle of rabbits with alloxan-induced diabetes. Such study may lead to therapeutic approaches for limiting the damage from oxidation reactions and preventing the diabetic complications.

High-performance liquid chromatographic assay of trandolapril in capsules.

Rapid, simple and accurate chromatographic (HPLC) method for the determination of trandolapril was elaborated. Samples were chromatographed on a LiChrosorb RP-18 column and the mobile phase was acetonitrile -0.067 M phosphate buffer pH 2.7 (7:3, v/v). The UV detection at 220 nm and benazepril as an internal standard were used. The method was tested for linearity (over the range 4-20 micrograms.ml-1), precision and accuracy and was successfully applied for the quantitative determination of trandolapril in capsules.

High-performance liquid chromatographic assay of dilazep in plasma after solid-phase extraction.

A new, simple and accurate high-performance liquid chromatography method is presented for measuring dilazep in plasma, using a reversed-phase technique and UV absorption at 267 nm. Dilazep and papaverine (the internal standard) added to plasma were successfully isolated using a solid-phase extraction procedure (CN cartridges). The method was linear between 2.5-12.5 micrograms ml-1. Over the tested concentration range the intra-day coefficient of variation for replicate analyses of plasma ranged from 2.38 to 5.27% (the day-to-day CV ranged from 2.52 to 7.99%). The detection limit for the analysis of dilazep in plasma was 50 ng with 20 microliters injection.

Determination of amiodarone in tablets and plasma by high-performance liquid chromatography.

A method is described for measuring amiodarone in human plasma and tablets using a LiChrosorb RP-18 column, a mobile phase methanol-acetonitrile-phosphate buffer pH 2.6 (80:15:5, v/v) and UV detection at 254 nm. Another antiarrhythmic drug - aprindine was used as an internal standard (i.s.).

Thin-layer chromatographic analysis of some benzofuran derivatives in human plasma.

Benzofuran derivatives: amiodarone, benziodarone, benzbromarone and benzarone, extracted from plasma, were separated by TLC method on silica gel by ascending and horizontal developments, using suitable mobile phases. The substances were identified by reaction with potassium permanganate solution, either by Dragendorff (modified after Amelink) or Sonnenschein reagents (up to the amounts of 250 ng of amiodarone and benzarone and 500 ng of benziodarone and benzbromarone).

Chromatographic analysis (TLC) aprindine and nadoxolol in human plasma.

Aprindine and nadoxolol extracted from plasma were separated by TLC method on silica gel by ascending technique on 5 x 20 cm and 2.5 x 7.5 cm microscopic slides and also by horizontal development, using suitable mobile phases. The substances were identified by reaction with Kiefer reagent (up to the amount 100 ng of aprindine and 300 ng of nadoxolol).