Disease relevance of trolox

• The hypersensitivity of the Q-deficient mutant can be rescued by the addition of butylated hydroxytoluene, alpha-tocopherol, or trolox, an aqueous soluble vitamin E analog [1].
• Furthermore, the combination of As(2)O(3) and trolox shows potential specificity for tumor cells, suggesting it may not increase the toxicity associated with As(2)O(3) monotherapy in vivo [2].
• We found that trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid), a widely known antioxidant, enhances As(2)O(3)-mediated apoptosis in APL, myeloma, and breast cancer cells [2].
• In both a global and partial model of hepatic ischemia-reperfusion in rats, infusion of Trolox (7.5 to 10 mumol/kg body weight) just before reflow reduced by greater than 80% the liver necrosis sustained in untreated (no Trolox) control rats [3].
• Antioxidants, including bovine liver catalase, bovine erythrocyte CuZn-SOD, sodium selenite and Trolox, a water soluble vitamin E analogue, as well as hypoxia, inhibited dexamethasone-induced apoptosis [4].

High impact information on trolox

• Treatment with As(2)O(3) and trolox increased intracellular oxidative stress, as evidenced by heme oxygenase-1 (HO-1) protein levels, c-Jun terminal kinase (JNK) activation, and protein and lipid oxidation [2].
• The synergistic effects of trolox may be specific to As(2)O(3), as trolox does not add to toxicity induced by other chemotherapeutic drugs [2].
• Trolox selectively enhances arsenic-mediated oxidative stress and apoptosis in APL and other malignant cell lines [2].
• There was release of mitochondrial cytochrome c into the cytosol and activation of caspase 3, which were prevented by cyclosporine, diallylsulfide, and Trolox [5].
• Trolox inhibits apoptosis in irradiated MOLT-4 lymphocytes [6].

Chemical compound and disease context of trolox

• This injury was accompanied by marked lipid peroxidation, and was strongly inhibited by hypoxia, by the antioxidants trolox, butylated hydroxytoluene and N-acetylcysteine and by the membrane-permeable iron chelators 2,2'-dipyridyl, 1,10-phenanthroline, LK 614, LK 616 and deferoxamine [7].
• A series of new compounds that contain lipoic acid and trolox connected through spacers were synthesized and examined for their antioxidant activity and their protective effects against reperfusion arrhythmias in isolated heart preparations [8].
• The antioxidants, Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid, a water soluble analog of vitamin E) and ascorbic acid (AA), protect the heart from ischemia-reperfusion injury [9].
• Antioxidants such as trolox or N-acetyl cysteine prevented this synergistic toxicity of SAMe plus AA or SAMe plus BSO, respectively [10].
• One mM WR 2721, 10 microM U83836E, and 5 microM trolox C reduced formation of malondialdehyde during hypoxia/reoxygenation to 53 +/- 7, 51 +/- 10 and 48 +/- 6%, respectively (P < 0.05 each, versus control) [11].

Biological context of trolox

• Levels of DNA fragmentation in cells not treated with trolox were directly related to both radiation dose and time postirradiation [6].
• In primary rat hepatocytes exposed to xanthine oxidase-hypoxanthine, lactosylphenyl Trolox prolonged cell survival better than did Trolox, mannitol or ascorbate [12].
• The treatment with Trolox C, in fact, almost completely prevented both liver necrosis and lipid peroxidation, while not changing at all the extent of the covalent binding of bromobenzene metabolites to liver protein [13].
• Also, increasing the pretreatment time of Trolox decreased the rate of cell death following UVB [14].
• Thus the marked difference between the rate and efficiency of ascorbate generation by dihydrolipoate as compared with GSH appears to account for the different kinetics by which these thiol antioxidants influence ascorbate-dependent Trolox recycling [15].

Anatomical context of trolox

• Here we examined the possible cytoprotective effect of Trolox in cultured hepatocytes and in the rat liver [3].
• Our results show the following: 1) E2 and Trolox attenuated the neurotoxicity mediated by A beta and H2O2 as measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assays, quantification of apoptotic cells, and morphological studies of the integrity of the neurite network [16].
• alpha-Tocopherol and trolox block the early intracellular events (TBARS and calcium rises) elicited by oxidized low density lipoproteins in cultured endothelial cells [17].
• On the other hand, diphenyleneiodonium and resiniferatoxin, inhibitors of plasma membrane oxidases, protected primary human fibroblasts against UVA, as potently as the lipid peroxidation chain breaker Trolox [18].
• The antioxidant activity of Trolox during peroxidation of membranes determined by measurements of the absolute rate constant for inhibition of oxygen uptake, kinh, was found to vary with the membrane surface charge that is controlled by variation in pH [19].

Associations of trolox with other chemical compounds

• In cultured rat hepatocytes, 0.5 to 16 mmol/L Trolox (with optimum between 1 to 2 mmol/L) was observed to prolong the survival of cells exposed to oxyradicals generated with xanthine oxidase-hypoxanthine [3].
• N-Acetyl-l-cysteine (NAC) but not other antioxidants, such as the vitamin E analog trolox and epigallocatechin-3-gallate, enhanced hypoxia-induced caspase-3 activation and apoptosis [20].
• Antioxidants, pyrrolidine dithiocarbamate, N-acetyl-L-cystein, and trolox effectively inhibited HG-induced NF-kappaB activation in MC [21].
• If the striatal tissue was incubated in either Trolox (alpha-tocopherol) or alpha-phenyl-n-tert-butyl nitrone (PBN) prior to OS, the negative effects of NO. and H2O2 were reversed in both age groups [22].
• Male Sprague-Dawley rats were fed either a vitamin E and selenium deficient diet, a diet supplemented with vitamin E and selenium, or a diet supplemented with vitamin E, selenium, trolox C, ascorbic acid palmitate, acetylcysteine, Beta-carotene, canthaxanthin, coenzyme Q0, coenzyme Q10, and (+)-catechin [23].

Gene context of trolox

• Trolox did not significantly affect UVB-induced phosphorylation of EGFR [14].
• NAC and Trolox also ameliorated AA-mediated Erk1/2 and p38 MAPK activation, suggesting that this activation is associated with ROS and oxidative stress [24].
• The fall in membrane potential was prevented by trolox and diallylsulfide, suggesting damage to the mitochondria by CYP2E1-derived reactive oxygen species [25].
• In addition, we found that both the water-soluble Vitamin E derivative, Trolox, and the green tea constituent, (-)-epigallocatechin gallate (EGCG), diminished AAPH-induced COX-2 expression and p38 activation [26].
• The expression of BCL-2 and BAX, which would occur downstream from p53, was not changed by irradiation and Trolox treatment [27].
• Ectopic overexpression of c-Fos rescued the inhibition of osteoclastogenesis by Trolox in bone marrow macrophages [28].

Analytical, diagnostic and therapeutic context of trolox

• Trolox protects rat hepatocytes against oxyradical damage and the ischemic rat liver from reperfusion injury [3].
• Rats were administered 625 microg/kg Trolox C, or vehicle, by intraperitoneal injection on alternate days for the duration of the exposure [29].
• Moreover, 20S proteasome activity in the diaphragm was elevated in the mechanical ventilation animals (+76%); Trolox treatment attenuated this mechanical ventilation-induced rise in protease activity [30].
• Gas chromatography analysis confirmed that effective myocardial levels of Trolox were attained [31].
• We have studied the effectiveness of intraperitoneal injection of Trolox C in an animal model of ROP [29].

References