Disease relevance of trientine

• The use of trientine in preventing the effects of interrupting penicillamine therapy in Wilson's disease [1].
• Trien is an effective cupruretic drug in primary biliary cirrhosis, but its use is limited by the occurrence of side effects that occurred in all 4 patients [2].
• We recently showed that treatment with the Cu(II)-selective chelator, trientine, alleviates heart failure in diabetic rats, improves left ventricular hypertrophy in humans with type 2 diabetes, and increases urinary Cu excretion in both diabetic rats and humans compared with nondiabetic control subjects [3].
• For initial therapy of patients with liver disease, we use a combination of zinc and trientine [4].
• The copper-chelating agent, trientine, suppresses tumor development and angiogenesis in the murine hepatocellular carcinoma cells [5].

High impact information on trientine

• A 20% reduction in sciatic nerve motor conduction velocity after 2 mo diabetes was 90% ameliorated by 2 wk of treatment with deferoxamine or trientine [6].
• We investigated whether chronic treatment with deferoxamine and trientine, transition metal chelating agents which can prevent autoxidation, could correct nerve conduction and blood flow changes in streptozotocin-diabetic rats [6].
• In most of the patients the toxic symptoms which forced a change of therapy were reversed on trien therapy; however, elastosis perforans did not seem to benefit, and two patients with penicillamine-induced systemic lupus erythematosus were not helped by the change [7].
• In the long-term administration of trientine, the incidence of hepatic cell carcinoma (HCC) in the treated rats was 67 percent that of the untreated LEC rats, and the number of HCCs per rat in the treated group was 0.7 +/- 0.5, being significantly lower as compared with 4.7 +/- 3.5 in the untreated rats [8].
• Trientine caused the Cu balance to become negative in diabetic subjects through elevated urinary Cu losses and suppressed elevated EC-SOD [3].

Chemical compound and disease context of trientine

• Twenty patients with Wilson's disease in whom severe penicillamine intolerance developed have been managed with the orally active chelating agent trientine dihydrochloride (trien) [7].
• SH-SY5Y neuroblastoma cells were cultured for up to three serial passages in the presence of the copper chelator triethylene tetramine (Trien) [9].
• OBJECTIVE: To compare tetrathiomolybdate and trientine in treating patients with the neurologic presentation of Wilson disease for the frequency of neurologic worsening, adverse effects, and degree of neurologic recovery [10].
• The efficacy of trientine or ascorbate alone compared to that of the combined treatment with these two agents in familial amyotrophic lateral sclerosis model mice [11].
• Treatment of Wilson disease has progressed from chelation therapy using D-penicillamine and trientine to the more recent use of zinc and finally to the establishment of liver transplantation as an urgent but excellent modality for fulminant presentation [12].

Biological context of trientine

• Kinetics of copper(II)--glycylglycyl-L-histidine reactions. Acid decomposition and proton-assisted nucleophilic displacement by triethylenetetramine [13].
• These results suggested that Cu plays a pivotal role in tumor development and angiogenesis in the murine HCC cells, and Cu-chelators, especially trientine, could inhibit angiogenesis and enhance apoptosis in the tumor with consequent suppression of the tumor growth in vivo [5].
• Trientine treatment resulted in a marked suppression of neovascularization and increase of apoptosis in the tumor, whereas tumor cell proliferation itself was not altered [5].
• They were synthesized in nonaqueous media from triethylenetetramine (TT) by monoalkylation of a primary amino group, followed by exhaustive carboxymethylation of the remaining amino groups using ethyl bromoacetate and subsequent alkaline hydrolysis of the ester [14].
• However, TETA and TEPA produced significant increases in the amount of UDS activity, and thus were considered positive in inducing primary DNA damage in this assay [15].

Anatomical context of trientine

• In addition, with a myeloid leukemic cell line (HL-60), triethylenetetramine inhibited SOD without causing significant GSH oxidation [16].
• Reversal treatment (4 weeks untreated diabetes, 4 weeks trientine) did not effect endothelium-dependent relaxation compared with aortas from rats with 4 weeks of diabetes, however, there was a 22.5 +/- 6.2% improvement compared with 8 weeks of diabetes [17].
• Ca uptake in rat liver mitochondria is accelerated by various aminoglucoside antibiotics and, to a lesser degree, by triethylenetetramine and by protamine [18].
• Treatment of the rat gastric fundus with the inhibitors of Cu/Zn SOD, diethyldithiocarbamate (DETC, 1 mM for 2 h) or triethylenetetramine (TETA, 100 microM for 2 h) had no effect on the relaxations to NANC nerve stimulation (1-8 Hz), NO (0.03-3 microM) or on those to ATP (10 microM) [19].
• Here we describe a highly reproducible in vivo model, in which hepatocytes are induced in the pancreas of adult rats that were maintained on copper-deficient diet containing a relatively non-toxic copper-chelating agent, triethylenetetramine tetrahydrochloride (0.6% w/w) for 7-9 weeks and then returned to normal rat chow [20].

Associations of trientine with other chemical compounds

• Equilibrium constants were determined by competition versus three different low molecular weight chelating agents: nitrilotriacetic acid, ethylenediamine-N,N'-diacetic acid, and triethylenetetramine [21].
• A possible shift from a ROS-mediated mutational spectrum to a spontaneous mutational spectrum by TRIEN further indicates that reactive oxygen species play an important role in bleomycin mutagenesis in mammalian cells [22].
• The affinity degree of BSA was higher than CEA for the EDA, HEDA and DETA columns, whereas the affinity degree of CEA was higher than BSA for the TETA column [23].
• A reducible poly(amido ethylenimine) (SS-PAEI) synthesized by addition copolymerization of triethylenetetramine and cystamine bis-acrylamide (poly(TETA/CBA)) was used as a carrier for small interference RNA (siRNA) [24].
• The bpy ligand is nearly planar in the X-ray structures of the complexes with (L)4 = (NH3)(4), triethylenetetraamine (trien), and 1,4,7,10-tetraazacyclododecane ([12]aneN4) [25].

Gene context of trientine

• We tested the copper chelators trientine, penicillamine, and bathophenanthroline for their ability to mobilize brain Abeta as measured against our benchmark compound bathocuproine (BC) [26].
• A combination regimen of trientine and methotrexate exerted the most potent tumoricidal effect and led to 'tumor dormancy.' The combination of these agents also resulted in a marked suppression of the angiogenic factors, in particular the vascular endothelial growth factor and interleukin-8, and an increase of apoptosis in the tumor [27].
• The production of IL-8 from the tumor was suppressed by trientine [28].
• Penicillamine has efficacy in rheumatoid arthritis and trientine has efficacy in diabetic neuropathy and diabetic heart disease [29].
• The copper chelator trientine has an antiangiogenic effect against hepatocellular carcinoma, possibly through inhibition of interleukin-8 production [28].

Analytical, diagnostic and therapeutic context of trientine

• We examined the effects of trientine on the spontaneous development of hepatitis and hepatic tumors, by its short-term and long-term administration to Long-Evans cinnamon (LEC) rats with an accumulation of copper in the liver, as animal models of Wilson's disease [8].
• Chelation therapy with penicillamine and trientine remain effective treatment for most symptomatic hepatic and neurologic Wilson disease [30].
• Trientine suppressed the growth of xenograft tumors significantly [28].
• The 67Ga and 68Ga complexes of H3[(5-MeOsal)3 TAME] and the bis(salicylaldimine) of triethylenetetramine were prepared and characterized by paper chromatography and electrophoresis [31].
• Triethylenetetramine (L(4)) was used as a tetradentate blocking ligand that, after complexation with Ni(II), leaves two sites ready for ligation with tricyanomethanide [32].

References