Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.17.3.2 (xanthine oxidase)
 8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We recently demonstrated that two new prenylflavanones, propolin A and propolin B, isolated and characterized from Taiwanese propolis, induced cytotoxicity effect in human melanoma A2058 cells and shows a strong capability to scavenge free radicals. In this study, propolin A effectively induced a cytotoxic effect on five different cancer cell lines. Similar results were obtained for propolin B. DNA flow cytometric analysis and DNA fragmentation ladder indicated that propolin A and propolin B actively induced apoptosis in A2058 cells. To address the mechanism of the apoptosis effect of propolin A and propolin B, we evaluated the apoptosis-related proteins in A2058 cells. The levels of procaspase-8, Bid, procaspase-3, DFF45, and PARP were decreased in dose- and time course-dependent manners. Furthermore, also found propolin A and propolin B was capable of releasing cytochrome c from mitochondria to cytosol. The findings suggest that propolin A and propolin B may activate a mitochondria-mediated apoptosis pathway. On the other hand, our data show that propolin B inhibitied xanthine oxidase activity more efficiently than propolin A or CAPE. However, CAPE suppressed ROS-induced DNA strand breakage more efficiently than propolin A or propolin B. All these results indicated that propolin A and propolin B may trigger apoptosis of A2058 cells through mitochondria-dependent pathways and also shown that propolin A and propolin B were strong antioxidants.
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PMID:Apoptosis of human melanoma cells induced by the novel compounds propolin A and propolin B from Taiwenese propolis. 1651 78

MK-801 was shown to be one of the most neurotoxic non-competitive NMDA receptor antagonists. It is known that repeated injection of MK-801 was proposed in an animal model in psychosis. The aims of this study are to investigate the contributing effect of oxidative stress in MK-801-induced experimental psychosis model, and to show that prevention of oxidative stress may improve prognosis. Furthermore, there is evidence that oxygen free radicals play an important role in the pathophysiology of schizophrenia. In this study, Wistar Albino rats were divided into three groups: 1st group: Control, 2nd group: MK-801, 3rd group: MK-801+CAPE (Caffeic acid phenethyl ester) group. MK-801 was given intraperitoneally at the dose of 0.5 mg/kg/day for 5 days. CAPE was given to the treatment group while exposed to MK-801. In control group, saline was given intraperitoneally at the same time. After 7 days, rats were killed by decapitation. Prefrontal cortex (PFC) of rats was removed for biochemical and histological analyses. As a result, malondialdehyde (MDA), protein carbonyl (PC), nitric oxide (NO) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and xanthine oxidase (XO) and adenosine deaminase (AD) enzyme activities were found to be increased significantly in prefrontal cortex (PFC) of MK-801 group (p<0.0001) compared to control group. In CAPE treated rats, prefrontal tissue MDA, PC, NO levels and, GSH-Px, XO, AD enzyme activities were significantly decreased when compared to MK-801 groups (p<0.0001) whereas catalase (CAT) enzyme activity was not changed. Moreover, in the light of microscopic examination of MK-801 groups, a great number of apoptotic cells were observed. CAPE treatment decreased the apoptotic cell count in PFC. The results of this study showed that MK-801-induced neurotoxicity caused oxidative stress in PFC of rats. This experimental study may also provide some evidences for the new treatment strategies with antioxidants in schizophrenia.
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PMID:Oxidative stress in prefrontal cortex of rat exposed to MK-801 and protective effects of CAPE. 1737 54

We employed the techniques of DNA relaxation, DPPH (1,1-diphenyl-2-picrylhydrazyl hydrate), and DMPO (5,5-dimethyl-1-pyrroline-N-oxide)-electron spin resonance (ESR), to study the effects of reactive oxygen species (ROS) suppression by 11 selected C6-C3 phenylpropanoid derivatives under oxidative conditions. We also investigated the effects of the derivatives on the inhibition of xanthine oxidase (XO) activity, and the structure-activity relationships (SARs) of these derivatives against XO activity were further examined using computer-aided molecular modeling. Caffeic acid was the most potent radical scavenger among the 11 test compounds. Our results suggest that the chemical structure and number of hydroxyl groups on the benzene ring of phenylpropanoids are correlated with the effects of ROS suppression. All test derivatives were competitive inhibitors of XO. The results of the structure-based molecular modeling exhibited interactions between phenylpropanoid derivatives and the molybdopterin region of XO. The para-hydroxyl of phenylpropanoid derivatives was pointed toward the guanidinium group of Arg 880. The phenylpropanoid derivatives containing the meta-or ortho-hydroxyl formed hydrogen bonds with Thr 1010. In addition, meta-hydroxyl formed hydrogen bonds with the peptide bond between the residues of Thr1010 and Phe1009. CAPE, the phenylenethyl ester of phenylpropanoids, had the highest affinity toward the binding site of XO, and we speculated that this was due to hydrophobic interactions of the phenylethyl ester with several hydrophobic residues surrounding the active site. The hypoxanthine/XO reaction in the DMPO-ESR technique was used to correlate the effects of these phenylpropanoid derivatives on enzyme inhibition and ROS suppression, and the results showed that caffeic acid and CAPE were the two most potent agents among the tested compounds. We further assessed the effects of the test compounds on living cells, and CAPE was the most potent agent for protecting cells against ROS-mediated damage among the tested phenylpropanoids.
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PMID:Structure-activity relationship of C6-C3 phenylpropanoids on xanthine oxidase-inhibiting and free radical-scavenging activities. 1796 25

Increased oxidative stress and associated high levels of free radical generation have been described to occur during the pathogeneses of various diseases in animal models. In the present work, we investigated the protective effects of the phenethyl ester of caffeic acid (CAPE), an active component of honeybee propolis, on tert-butyl hydroperoxide (t-BHP)-induced hepatotoxicity in a cultured HepG2 cell line and in rat liver. CAPE was found to significantly reduce t-BHP-induced oxidative injury in HepG2 cells, as determined by cell cytotoxicity, and lipid peroxidation and reactive oxygen species (ROS) levels in a dose-dependent manner. Furthermore, CAPE protected HepG2 cells against t-BHP-induced oxidative DNA damage, as determined by the Comet assay. Consistently, CAPE reduced hydroxyl radical-induced 2-deoxy-d-ribose degradation by ferric ion-nitrilotriacetic acid and H2O2, and also removed the superoxide anion generated by a xanthine/xanthine oxidase system. Our in vivo study showed that pretreatment with CAPE prior to the administration of t-BHP significantly and dose-dependently prevented increases in the serum levels of hepatic enzyme markers (alanine aminotransferase and aspartate aminotransferase) and reduced lipid peroxidation in rat liver. Moreover, histopathological evaluation of livers consistently revealed that CAPE reduced liver lesion induction by t-BHP. Taken together, these results suggest that the protective effects of CAPE against t-BHP-induced hepatotoxicity may, at least in part, be due to its ability to scavenge ROS and protect DNA from oxidative stress-induced damage.
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PMID:Protective effect of caffeic acid phenethyl ester on tert-butyl hydroperoxide-induced oxidative hepatotoxicity and DNA damage. 1848 57