1.A yeast bioassay for direct measurement of thyroid hormone disrupting effects in water without sample extraction, concentration, or sterilization.
Li J1, Ren S2, Han S2, Li N3. Chemosphere. 2014 Apr;100:139-45. doi: 10.1016/j.chemosphere.2013.11.054. Epub 2013 Dec 16.
The present study introduces an improved yeast bioassay for rapid yet sensitive evaluation of thyroid hormone disruption at the level of thyroid receptor (TR) in environmental water samples. This assay does not require water sample preparation and thus requires very little hands-on time. Based on different β-galactosidase substrates, two modified bioassays, a colorimetric bioassay and a chemiluminescent bioassay, were developed. The compounds tested included the known thyroid hormone 3,3',5-triiodo-l-thyronine (T3), the specific TR antagonist amiodarone hydrochloride (AH) and phthalate esters (PAEs), which potentially disrupt thyroid hormone signaling. The EC50 values for T3 were similar to those previously obtained using a 96-well plate bioassay. TR antagonism by AH was studied in the presence of 2.5 × 10(-7)M T3, and the concentration producing 20% of the maximum effect (RIC20) for AH was 3.1 × 10(-7)M and 7.8 × 10(-9)M for the colorimetric bioassay and chemiluminescent bioassay, respectively.
2.Antitumor actions of ruthenium(III)-based nitric oxide scavengers and nitric oxide synthase inhibitors.
Flitney FW1, Pritchard RJ, Kennovin GD, Bisland SK, Hirst DG, Fricker SP. Mol Cancer Ther. 2011 Sep;10(9):1571-80. doi: 10.1158/1535-7163.MCT-10-0840. Epub 2011 Jun 28.
The role of endogenous nitric oxide (NO) in the growth and vascularization of a rat carcinosarcoma (P22) has been investigated. Tumor-bearing animals were treated with (i) nitric oxide synthase (NOS) inhibitors, administered via the drinking water, including N(G)-nitro-l-arginine methyl ester (L-NAME), a nonisoform-selective inhibitor, and 2 others that target the inducible (NOS II) enzyme preferentially, namely 1-amino-2-hydroxyguanidine or N-[3-(aminomethyl)benzyl]acetamidine hydrochloride; or (ii) daily injections (intraperitoneally) of 2 Ru(III) polyaminocarboxylates, AMD6221 and AMD6245, both of which are effective NO scavengers. L-NAME, AMD6221, and AMD6245 reduced tumor growth by approximately 60% to 75% of control rates. Tumor sections stained with abs to CD-31/platelet endothelial cell adhesion molecule-1 or NOS III showed that this was associated with a marked reduction (60%-77%) of tumor microvascular densitiy (MVD). Tumors resumed growing promptly when treatment was discontinued, accompanied by partial or complete restoration of MVDs.
3.Sepsis worsening vascular hyporeactivity of the superior mesenteric artery in portal vein-ligated rats.
Liao WC1, Hou MC, Wang GJ, Yu KW, Lee FY, Lin HC, Lee SD. J Chin Med Assoc. 2010 Sep;73(9):462-70. doi: 10.1016/S1726-4901(10)70100-3.
BACKGROUND: Vascular hyporeactivity is observed in portal hypertensive animals and septic rats. The objective of this study was to investigate whether impairment of superior mesenteric artery vascular contractility in the portal hypertensive rat was further impaired after sepsis.
4.YC-1 stimulates the expression of gaseous monoxide-generating enzymes in vascular smooth muscle cells.
Liu XM1, Peyton KJ, Mendelev NN, Wang H, Tulis DA, Durante W. Mol Pharmacol. 2009 Jan;75(1):208-17. doi: 10.1124/mol.108.048314. Epub 2008 Oct 15.
The benzylindazole derivative 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1) is an allosteric stimulator of soluble guanylate cyclase (sGC) that sensitizes the enzyme to the gaseous ligands carbon monoxide (CO) and nitric oxide (NO). In this study, we examined whether YC-1 also promotes the production of these gaseous monoxides by stimulating the expression of the inducible isoforms of heme oxygenase (HO-1) and NO synthase (iNOS) in vascular smooth muscle cells (SMCs). YC-1 increased HO-1 mRNA, protein, and promoter activity and potentiated cytokine-mediated expression of iNOS protein and NO synthesis by SMCs. The induction of HO-1 by YC-1 was unchanged by the sGC inhibitor, 1H-(1,2,4)oxadiazolo[4,3-alpha]quinozalin-1-one (ODQ) or by the protein kinase G inhibitors (8R,9S,11S)-(-)-2-methyl-9-methoxyl-9-methoxycarbonyl-8-methyl-2,3,9,10-tetrahydro-8,11-epoxy-1H,8H,11H-2,7b,11a-triazadibenzo(a,g)cyclocta9(cde)trinen-1-one (KT 5823) and YGRKKRRQRRRPPLRKKKKKH-amide (DT-2) and was not duplicated by 8-bromo-cGMP or the NO-independent sGC stimulator 5-cyclopropyl-2[1-(2-fluorobenzyl)-1H-pyrazolo [3,4-b] pyridine-3-yl] pyrimidin-4-ylamine (BAY 41-2272).
