It is established, that alpha-tocopherol and pioglitazone in concentration up to 100 microM did not change the rat thymocytes viability while troglitazone and alpha-tocopherol with a short side chain up to 6 atoms of carbon (alpha-tocopherol C6) have the expressed cytotoxic effect. This is the first report demonstrating that troglitazone and alpha-tocopherol C6, unlike a-tocopherol and pioglitazone substantially inhibited the activity of NAD(P)H:quinone oxidoreductase (DT-diaphorase) and this effect is increased with specific DT-diaphorase inhibitor, dicoumarol. Based on these observations, we generalize that cytotoxic action of troglitazone and alpha-tocopherol C6 is connected with the presence in their structure of chroman ring with a lateral chain modified in relation to alpha-tocopherol and is mediated by inhibition of DT-diaphorase, a detoxifying enzyme of xenobiotics.
Download full-text PDF |
Source |
|---|
Publication Analysis
Top Keywords
Similar Publications
15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) protects neurons from oxidative death via an Nrf2 astrocyte-specific mechanism independent of PPARγ.
J Neurochem
February 2013
The Burke Medical Research Institute, Department of Neurology and Neuroscience, Weill Medical College of Cornell University, White Plains, NY 10605, USA.
Astrocytes are critical for the antioxidant support of neurons. Recently, we demonstrated that low level hydrogen peroxide (H(2) O(2) ) facilitates astrocyte-dependent neuroprotection independent of the antioxidant transcription factor Nrf2, leaving the identity of the endogenous astrocytic Nrf2 activator to question. In this study, we show that an endogenous electrophile, 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), non-cell autonomously protects neurons from death induced by depletion of the major antioxidant glutathione.
View Article and Find Full Text PDFIt is established, that alpha-tocopherol and pioglitazone in concentration up to 100 microM did not change the rat thymocytes viability while troglitazone and alpha-tocopherol with a short side chain up to 6 atoms of carbon (alpha-tocopherol C6) have the expressed cytotoxic effect. This is the first report demonstrating that troglitazone and alpha-tocopherol C6, unlike a-tocopherol and pioglitazone substantially inhibited the activity of NAD(P)H:quinone oxidoreductase (DT-diaphorase) and this effect is increased with specific DT-diaphorase inhibitor, dicoumarol. Based on these observations, we generalize that cytotoxic action of troglitazone and alpha-tocopherol C6 is connected with the presence in their structure of chroman ring with a lateral chain modified in relation to alpha-tocopherol and is mediated by inhibition of DT-diaphorase, a detoxifying enzyme of xenobiotics.
View Article and Find Full Text PDFDifferential modulation of farnesoid X receptor signaling pathway by the thiazolidinediones.
J Pharmacol Exp Ther
July 2009
Department of Biomedical and Pharmaceutical Sciences, Center for Pharmacogenomics and Molecular Therapy, College of Pharmacy, University of Rhode Island, 41 Lower College Rd., Kingston, RI 02881, USA.
Thiazolidinediones (TZD), including troglitazone, rosiglitazone, and pioglitazone, are agonists of peroxisome proliferator-activated receptor (PPAR)-gamma and belong to a class of insulin-sensitizing drugs for type 2 diabetes mellitus. However, member-specific, PPARgamma-independent activities and toxicity have been reported, especially for troglitazone. Currently, the underlying mechanisms are not fully understood.
View Article and Find Full Text PDFAlpha-tocopherol modulates human umbilical vein endothelial cell expression of Cu/Zn superoxide dismutase and catalase and lipid peroxidation.
Nutr Res
October 2008
Department of Nutrition and Environmental Sciences and Health Graduate Program, University of Nevada, Reno, NV 89557, USA.
Recent studies suggest the potential of alpha-tocopherol as a gene regulator, possibly through peroxisome proliferator-activated receptor gamma (PPARgamma) activation due to the structural similarity of alpha-tocopherol to a PPARgamma ligand, troglitazone. Other investigators have suggested that a link exists between induction of the antioxidant enzymes Cu/Zn superoxide dismutase (SOD) and catalase and PPARgamma activation. This study was designed to examine whether alpha-tocopherol modulates expression of Cu/Zn SOD and catalase in human umbilical vein endothelial cells through redox-sensitive transcription factors, PPARgamma, and nuclear factor-kappaB (NF-kappaB).
View Article and Find Full Text PDFPhosphorylated troglitazone activates PPARgamma and inhibits vascular smooth muscle cell proliferation and proteoglycan synthesis.
J Cardiovasc Pharmacol
March 2008
Cell Biology of Diabetes Laboratory, Baker Heart Research Institute, Melbourne, Australia.
Phosphorylation of alpha-tocopherol produces an entity with enhanced antiatherogenic properties. Troglitazone, an alpha-tocopherol derivative of a 2,4-thiazolidinedione nucleus, is an antidiabetic agent that shows fatal idiosyncratic hepatotoxicity, a property not shared by later agents. We investigated the effects of phosphorylation of troglitazone (to yield "phosphoglitazone") on the biochemical pharmacologic properties of troglitazone.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!