Effect of the new thiazolidinedione-pioglitazone on the development of oxidative stress in liver and kidney of diabetic rabbits

Department of Medicinal Chemistry, Faculty of Pharmacy, Medical University of Lublin, Chodźki Str 6, 20-093 Lublin, Poland.
Life Sciences (Impact Factor: 2.3). 01/2004; 74(5):553-62. DOI: 10.1016/j.lfs.2003.03.004
Source: PubMed

ABSTRACT Impaired homeostasis under diabetic conditions is connected with the increased production of free radicals and deficiency of antioxidative systems. The aim of this study was to analyze the effect of new oral antidiabetic drug-pioglitazone on activity of antioxidant factors and lipid peroxidation in vivo. The liver and kidney of alloxan-induced diabetic rabbits were examined after 4 and 8 weeks of treatment. After 4 weeks of diabetes the superoxide dismutase (Cu,Zn-SOD) activity in the liver was diminished while the catalase (CAT) activity and the level of ascorbic acid (AA) were elevated in comparison with the control group. Pioglitazone treatment during 4 weeks decreased the catalase activity in relation to the control diabetic animals. After 8 weeks of diabetes the CAT activity in the liver was elevated in comparison with the control group. Pioglitazone treatment during 8 weeks decreased the CAT activity and the level of lipid peroxidation products (LPO), and increased the Cu,Zn-SOD activity in relation to control diabetic animals. After 4 weeks of diabetes in the kidney the Cu,Zn-SOD activity and the level of ascorbic acid (AA) were diminished while the CAT activity and the LPO level were elevated in comparison with the control group. Pioglitazone treatment during 4 weeks increased the AA and decreased the LPO levels in relation to non-treated diabetic animals. After 8 weeks of disease the Cu,Zn-SOD activity in the kidney was diminished in comparison with the control group. Pioglitazone during 8 weeks decreased the LPO level in relation to non-treated diabetic animals. This study shows that diabetic animals undergo an important oxidative stress, which is partially corrected by pioglitazone treatment.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Glitazones rank now among the most used hypoglycemic agents in patients with type-2 diabetes. This systematic review focuses on the cardiovascular and renal outcomes in chronic kidney disease (CKD) patients treated with these drugs. Data from randomized clinical trials and a meta-analysis indicate that glitazones (particularly rosiglitazone) may increase the risk of myocardial infarction, heart failure and cardiovascular death in type-2 diabetics. Observational studies looking at survival and cardiovascular outcomes in diabetic patients with kidney failure show controversial results. Studies in experimental models and clinical studies suggest that glitazones may have favorable effects on renal disease progression, because these drugs coherently reduce urinary albumin excretion and proteinuria in diabetic and non-diabetic nephropathies. No clinical trial based on clinical end-points like kidney failure has until now tested the effect of glitazones on the evolution of chronic renal failure in these patients. Whether the use of glitazones has a positive or a negative impact upon major cardiovascular and renal outcomes in diabetic patients remains an open, unanswered question. Specific studies are needed to assess the efficacy and safety of glitazones in a high risk population like type-2 diabetics with chronic kidney disease.
    Nutrition, metabolism, and cardiovascular diseases: NMCD 03/2012; 22(3):167-75. DOI:10.1016/j.numecd.2011.11.005 · 3.88 Impact Factor
  • Source
    Nutrition Metabolism and Cardiovascular Diseases 03/2012; · 3.88 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Baicalin, a herb-derived flavonoid compound, has beneficial activities, including the modulation of oxidative stress and inflammation. Nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ) is a ligand-activated transcription factor that plays an important role in regulating nuclear factor-κB (NF-κB)-induced age-related inflammation. We investigated the anti-inflammatory action of baicalin, which depends on its ability to activate PPARγ, and subsequently to suppress NF-κB. We examined baicalin-treated kidney tissue from 24-month-old Fischer 344 aged rats (10 or 20 mg/kg/day for 10 days) and baicalin-fed mice (10 mg/kg/day for 3 days) for in vivo investigations, and used endothelial YPEN-1 cells for in vitro studies. In the baicalin-fed aged rats, there was a marked enhancement of both nuclear protein levels and DNA binding activity of PPARγ, and a decreased expression of NF-κB target genes (VCAM-1, IL-1β, and IL-6) compared with non-baicalin-fed aged rats. Furthermore, to confirm the anti-inflammatory action of PPARγ activated by baicalin, we used lipopolysaccharide (LPS)-treated cells and mice. The results showed that baicalin induced PPARγ-selective activation in YPEN-1 cells, and that the effects of baicalin were blocked by the PPARγ receptor antagonist, GW9662. In addition, baicalin treatment prevented RS generation, NF-κB activation and the expression of pro-inflammatory genes, whereas it increased PPARγ expression in LPS-treated cells and mouse kidney. Our data suggest that baicalin-induced PPARγ expression reduced age-related inflammation through blocking pro-inflammatory NF-κB activation. These results indicate that baicalin is a novel PPARγ activator and that this agent may have the potential to minimize inflammation.
    Biogerontology 10/2011; 13(2):133-45. DOI:10.1007/s10522-011-9361-4 · 3.01 Impact Factor