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)

A number of immunomodulating agents of different origin have been shown to reduce liver injury of various etiologies. Immunostimulants like levamisole, BCG, a protein polysaccharide from myceria Coriolus vesicolor PS-K, a streptoccocal preparation OK-432 and immunomodulators like N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) and its analogs. Selective T-cell suppressors like the polypeptide cyclosporine A (CsA) and the macrolide FK 506 (tacrolimus) have also been claimed to possess hepatoprotrophic or hepatoprotective properties at low doses. The aim of this review article is to highlight the interplay between the administration of immunomodulating agents and the amelioration of hepatic injuries. Hepatic effects of exogenous immunomodulators are discussed with special focus on the most widely used immunosuppressive agents, CsA and tacrolimus. An important question exists as to whether these potential hepatoprotective effects are related mechanistically to the immune system or are working at different levels. Due to the differences in effects and modes of actions of various immunoactive substances presented herein, a common mechanism for their cytoprotective effects cannot be formulated at this stage. Levamisole and cyanidanol may protect cells against necrosis by acting as free radical scavengers. MDP and its analogs reduce carbon tetrachloride-elevated (CCl4) lipid peroxides and their protective effects are primarily on hepatic cytoplasmic membranes where lipid peroxidation and calcium homeostasis interact. MDP reduced CCl4-elevated calcium in both intact hepatocytes and in the post microsomal supernatant suggest that the influx of extracellular calcium across plasma membrane is affected. Elevations of intracellular calcium above a threshold are involved in: the stimulation of Ca2+-sensitive enzymes such as phospholipase A2, endonucleases and proteases, the conversion of xanthine dehydrogenase to xanthine oxidase and the formation of free radicals, all of which disturb biomembranes. MDP and its analogs, in a specific dose range, may act to maintain intracellular calcium within physiological ranges. Highly complex cellular signalling systems, including calcium, are involved in the explanation of the mechanism of the immunosuppressive effect of CsA and tacrolimus. The hepatoprotective effects of these selective immunosuppressive agents, however, are independent of the inhibition of T-cell activation. The cyclophilin and tacrolimus binding proteins of the mitochondria are the receptors for these compounds and play a key role in the regulation of mitochondrial permeability transition pores. CsA or tacrolimus inhibition of mitochondrial permeability transition pores does not require interaction with calcineurin, indicating a dissociation between immunosuppression and mitochondrial protection. The involvement of intracellular or intramitochondrial proteins in the modulation of mitochondrial permeability transition pores with the creation of a partially impermeable state for Ca2+ movement in drug-treated mitochondria and the dissociation of this effect from immunomodulatory actions potentially offers new and promising approaches for the development of new pharmacologicals targeted at therapeutic intervention. Clinical trials of these drugs as hepatoprotective agents are limited. Use of CsA in patients with primary biliary cirrhosis and autoimmune chronic hepatitis and in cirrhotic animal models produced by chronic administration of CCl4 have yielded encouraging results. It seems that this class of compounds may be of substantial benefit in liver protection against many pathological conditions where disturbance in mitochondrial function and in Ca2+ homeostasis appear to be prerequisites for cell injury.
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PMID:Immunopharmacologic agents in the amelioration of hepatic injuries. 973 Feb 49

The Chinese herbal medicine sho-saiko-to is a mixture of seven herbal components (Bupleurum root, Pinellia tuber, Scutellaria root, Jujube fruit, Ginseng root, Glycyrrhiza root and Ginger rhizome) that is widely administered to patients with chronic hepatitis in Japan. We assessed the effects of sho-saiko-to on the activity of cytochrome P450 (CYP) 1A2, CYP3A and xanthine oxidase (XO) in man. Twenty-six healthy subjects were studied to evaluate their baseline activity of CYP1A2 and XO by the respective urinary metabolic ratios of an 8-h urine sample after an oral 150-mg dose of caffeine and of CYP3A by a urinary excretion ratio of 6beta-hydroxycortisol (6beta-HC) to free cortisol (FC). Thereafter, the subjects received a twice-daily 2.5-g dose of sho-saiko-to for five days, and underwent the caffeine test on day 1 and day 5. The mean activity of CYP1A2 decreased by 16% on both day 1 and day 5 compared with the baseline (P=0.001). The mean activity of XO also significantly decreased by 25% on day 1 and 20% on day 5 (P<0.0001) compared with the baseline value. The activity of CYP3A tended to be lower on day 5 than the baseline (P=0.146). It is concluded that sho-saiko-to reduces CYP1A2 and XO activity in man.
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PMID:The in-vivo effects of sho-saiko-to, a traditional Chinese herbal medicine, on two cytochrome P450 enzymes (1A2 and 3A) and xanthine oxidase in man. 1471 67

Type I interferon receptor (IFNAR) has been involved in the progression of chronic hepatitis B (CHB). Oxidative stress is also associated with hepatitis B virus (HBV) infection and might contribute to the structure and function of protein synthesis including the IFNAR family. This study was aimed to determine the possible associations between oxidative stress and peripheral IFNAR expression in chronic HBV infection. Fifty-four CHB patients and 31 liver cirrhosis (LC) patients were consecutively collected, as well as 11 healthy subjects as controls. Expression levels of IFNAR1 and IFNAR2 in peripheral blood lymphocytes and monocytes were measured by flow cytometry. IFNAR1 and IFNAR2c mRNA were detected by real-time reverse transcription-polymerase chain reaction. Levels of plasma-soluble IFNAR and oxidative stress parameters, including xanthine oxidase (XOD), malondialdehyde (MDA), glutathione (GSH), glutathione S-transferase (GST), and glutathione peroxidase (GSH-Px) were detected by enzyme linked immunosorbent assay (ELISA). The frequencies of IFNAR1 and IFNAR2 in lymphocytes and monocytes were significantly increased in CHB and LC patients than in healthy controls. Expression levels of IFNAR1 and IFNAR2c mRNA and plasma-soluble IFNAR level in CHB and LC patients were upregulated compared with healthy controls. Mean fluorescence intensity (MFI) of IFNAR2 in monocytes of CHB patients was higher than that in LC patients. Levels of plasma XOD, MDA, and GST were significantly increased in CHB and LC patients compared with healthy controls. Meanwhile, GSH and GSH-Px in CHB and LC patients were decreased than that in healthy controls. Furthermore, plasma MDA, GSH, and GST levels in CHB patients were higher than that in LC patients. In CHB patients, plasma GST level was negatively correlated with MFI of IFNAR2 in lymphocytes. Our results suggested that oxidative stress play an important role in the regulation of IFNAR in chronic HBV infection.
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PMID:Peripheral type I interferon receptor correlated with oxidative stress in chronic hepatitis B virus infection. 2366 46

Jia-wei-xiao-yao-san (JWXYS) is a traditional Chinese herbal medicine that is widely used to treat neuropsychological disorders. Only a few of the hepatoprotective effects of JWXYS have been studied. The aim of this study was to investigate the hepatoprotective effects of JWXYS on dimethylnitrosamine- (DMN-) induced chronic hepatitis and hepatic fibrosis in rats and to clarify the mechanism through which JWXYS exerts these effects. After the rats were treated with DMN for 3 weeks, serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) levels were significantly elevated, whereas the albumin level decreased. Although DMN was continually administered, after the 3 doses of JWXYS were orally administered, the SGOT and SGPT levels significantly decreased and the albumin level was significantly elevated. In addition, JWXYS treatment prevented liver fibrosis induced by DMN. JWXYS exhibited superoxide-dismutase-like activity and dose-dependently inhibited DMN-induced lipid peroxidation and xanthine oxidase activity in the liver of rats. Our findings suggest that JWXYS exerts antifibrotic effects against DMN-induced chronic hepatic injury. The possible mechanism is at least partially attributable to the ability of JWXYS to inhibit reactive-oxygen-species-induced membrane lipid peroxidation.
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PMID:A Chinese herbal medicine, jia-wei-xiao-yao-san, prevents dimethylnitrosamine-induced hepatic fibrosis in rats. 2499 53