Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The elimination and distribution of phenylbutazone after administration of a single intravenous dose of 25 mg/kg was investigated before and at different stages of adjuvant-induced arthritis in the same group of rats. In other groups which were studied concurrently, the cytochrome P-450 and b5 levels and ethylmorphine demethylation of liver microsomes were determined. Total plasma protein and albumin concentrations were monitored and the binding of phenylbutazone to plasma proteins was investigated. In the acute phase of adjuvant-induced arthritis, there was 1) a pronounced decrease in the elimination rate of phenylbutazone and 2) a marked increase in the apparent volume of distribution. The former could be explained by a reduced rate of hepatic biotransformation of phenylbutazone. A pronounced decrease in the microsomal cytochrome content and a slow rate of ethylmorphine demethylation is in agreement with this assumption. The latter appeared to be a result of the reduced binding capacity of the rat plasma due to the decrease in albumin concentration. The cytochrome content of liver microsomes and the plasma albumin concentration, however, were restored when arthritis reached its chronic phase. Consequently, an impairment of the elmination and distribution of phenylbutazone was no longer apparent.
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PMID:Elimination and distribution of phenylbutazone in rats during the course of adjuvant-induced arthritis. 127 Dec 89

Changes in the total cobalamin content and spectrum of individual forms of these vitamins in blood cells and plasma as well as the activities of enzymatic systems of xenobiotic metabolism in liver microsomes of rats with experimental adjuvant arthritis (AA) have been studied. The total cobalamin content in the blood plasma of rats with AA was increased in comparison with intact animals; however, leucocytes from AA rats were deficient in methylcobalamin (MeCbl). A correlation was found between the ratios of individual cobalamin forms and their total content which was differently expressed in experimental and control animals. The development of AA was associated with marked inhibition of the cytochrome P-450-dependent monooxygenase system of the liver and glutathione transferase. The possibility of correction of these disturbances by MeCbl is discussed.
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PMID:[Blood cobalamins and xenobiotic-metabolizing enzymes in rat liver in adjuvant arthritis]. 148 28

Differential metabolism of 25-hydroxyvitamin D3 (25(OH)D3) has been shown for macrophages and fibroblast-like cells (possibly synoviocytes) cultured for two to 50 days after isolation from the synovial fluid of 12 patients with various forms of inflammatory arthritis. Macrophages synthesised the active metabolite of vitamin D3, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the synthesis of which was increased by bacterial lipopolysaccharide, a known macrophage activating factor. In contrast, fibroblast-like cells formed 24, 25-dihydroxyvitamin D3 (24,25(OH)2D3), synthesis of which was stimulated by 1,25(OH)2D3 and inhibited by lipopolysaccharide. The synthesis of 1,25(OH)2D3 and 24,25(OH)2D3 by macrophages and fibroblast-like cells respectively was inhibited by ketoconazole, indicating that both hydroxylases are dependent on cytochrome P-450. Mean (SEM) synovial fluid and serum 25(OH)D3 concentrations were 16.7 (1.7) and 22.2 (2.6) ng/ml and those of 1,25(OH)2D3 were 29.4 (4.8) and 43.3 (4.0) pg/ml respectively. In most cases concentrations were lower in synovial fluid than in paired serum samples, but in two patients 1,25(OH)2D3 concentrations were greater in synovial fluid than in serum, suggesting local synthesis within the affected joints.
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PMID:Differential metabolism of 25-hydroxyvitamin D3 by cultured synovial fluid macrophages and fibroblast-like cells from patients with arthritis. 155 Apr 7

1. M. butyricum administration to rats induces arthritis and impairment in hepatic cytochrome P-450 activity. 2. This work was performed to verify if M. butyricum administrated to mice produces similar effects on cytochrome P-450 hepatic without involvement of articular lesions. 3. We also studied the role of arachidonate metabolites in the genesis and perpetuation of hepatic injury. 4. Intraperitoneal M. butyricum administration to mice increased sleeping time induced by pentobarbital and decreased both aminopyrine N-demethylase (AND) and aniline p-hydroxylase (APH) activities without producing articular inflammation. 5. Only preventative oral administration of indomethacin or dexamethasone during the week before M. butyricum injection avoided drug-metabolizing system alterations. 6. Our results suggest a possible link between arachidonate metabolites inhibited by indomethacin or dexamethasone and the genesis of cytochrome P-450 disfunction.
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PMID:Effect of Mycobacterium butyricum on the hepatic cytochrome P-450 system of the mouse: influence of anti-inflammatory drug. 167 74

Enzyme-inducing drugs such as phenobarbital (PB) increase serum concentrations of an acute-phase protein, alpha 1-acid glycoprotein (AGP), in man, dogs, and rats via an unknown mechanism. We studied the effects of PB on components of an acute inflammatory reaction in rats in order to determine if PB acts only on this biological marker of inflammation or is capable of altering the clinical course of inflammatory processes. Local carrageenan injection induces a similar time-dependent plantar edema and increases serum AGP levels in Sprague-Dawley (SD) and Dark Agouti (DA) rats. Pretreatment with PB for seven days modified neither parameter in SD rats while plantar edema was aggravated and serum AGP levels were increased in DA rats. The sedative-hypnotic properties of PB were not involved, since a single administration of this drug had no action in DA rats. On the other hand, chronic PB administration reduced the severity of an autoimmune disease, type II collagen-induced arthritis, in DA rats. These data indicate that PB, a potent inducer a cytochrome P-450-dependent enzymes, modifies the course of the inflammatory process. Preliminary results with macrophage transfer experiments suggest that this response to PB could be mediated by stimulated macrophages.
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PMID:Modification of inflammatory processes by phenobarbital in rats. 175 30

Hepatic microsomal estrogen metabolism was analyzed in the (New Zealand black x New Zealand white)F1 ([NZB x NZW]F1) murine model of systemic lupus erythematosus. Both the estrogen 2-hydroxylase activity (per mg microsomal protein) and the hepatic cytochrome P-450 content were higher in premorbid (NZB x NZW)F1 mice, as compared with similarly aged nonautoimmune mice. However, these differences were not associated with alterations in the relative formation of the 2-hydroxylated and the 16 alpha-hydroxylated metabolites. The development of overt nephritis was associated with a decrease in estrogen metabolic activity, but not with any alteration in the distribution of estrogen metabolites. Thus, estrogen metabolism was not altered in premorbid (NZB x NZW)F1 mice in a manner that would result in abnormal retention of hormonally active metabolites.
Arthritis Rheum 1990 Jan
PMID:Estrogen metabolism in the (New Zealand black x New Zealand white)F1 murine model of systemic lupus erythematosus. 230 61

Oxidative metabolism in patients with systemic lupus erythematosus (SLE) was studied using the antihypertensive drug, debrisoquine. The metabolism of this drug to its principal metabolite, 4-hydroxydebrisoquine, is catalyzed by a discrete isozyme of cytochrome P-450. The extent of this reaction exhibits genetic polymorphism, with 2 phenotypes, "poor metabolizers" and "extensive metabolizers," discernible in the normal population. We observed the poor metabolizer debrisoquine phenotype in 9 of 42 patients with idiopathic SLE (21%), in contrast with 12 of 147 healthy volunteers (8%), which is a significant difference in frequency (P less than 0.04). These data provide further evidence for altered oxidative metabolism in SLE and support the concept that genetic differences in oxidative metabolism of endogenous compounds, such as sex steroid hormones, or of xenobiotics might influence susceptibility to SLE.
Arthritis Rheum 1986 Jul
PMID:Altered distribution of debrisoquine oxidation phenotypes in patients with systemic lupus erythematosus. 374

1. Adjuvant-induced arthritis in rats is accompanied by a loss of activity of the drug-metabolizing enzyme system and a decrease in hepatic cytochrome P-450. 2. Arthritic rats have normal serum and liver cholesterol concentrations. 3. The rate of biogenesis of cholesterol in vivo and in vitro from either [(14)C]acetate or [(14)C]mevalonate in arthritic rats was the same as or greater than that found in control rats. 4. Treatment of rats with carbon disulphide (1ml/kg) resulted in a loss of drug-metabolizing-enzyme activity and increased cholesterol biogenesis. 5. The activity of cholesterol 7alpha-hydroxylase in adjuvant-induced arthritic rats did not differ significantly from that in control rats. 6. Rats fed with cholestyramine had an elevated hepatic cholesterol 7alpha-hydroxylase activity, but neither the concentration of cytochrome P-450 nor the activity of the drug-hydroxylating enzyme, aminopyrine demethylase, was affected. 7. The relationships between drug hydroxylation and cholesterol metabolism are discussed.
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PMID:The role of cytochrome P-450 in cholesterol biogenesis and catabolism. 508 88

The ability of honeybee venom to suppress Mycobacterium butyricum-induced arthritis was studied in Lewis rats. Bee venom, 2 mg.kg-1.day-1 for 24 days, suppressed but did not abolish the primary and secondary inflammatory responses to the adjuvant as monitored by decreases in the swelling of the left and right hind paws and adjuvant-induced arthritis on heme metabolism were also examined. Bee venom or adjuvant had no effect on hepatic delta-aminolevulinic acid synthase, porphyrin content, or ferrochelatase activity. However, with both treatments cytochrome P-450 and the associated enzymic activities of ethylmorphine N-demethylase and benzo[a]pyrene hydroxylase were depressed markedly. In contrast, both treatments caused several-fold enhancement of hepatic microsomal heme oxygenase activity. Adjuvant-treated rats receiving bee venom showed changes in heme metabolism which were of a magnitude similar to those observed when either agent was administered to the experimental animals. Although the bee venom appears to suppress adjuvant-induced arthritis to a greater extent in female than in male rats, the alterations in heme metabolism were similar in bee venom-treated male and female rats. The observed changes in heme metabolism elicited by the venom or by the adjuvant are strongly suggestive of perturbations of the immune system causing alterations in hepatic microsomal enzymes.
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PMID:Effect of honeybee (Apis mellifera) venom on the course of adjuvant-induced arthritis and depression of drug metabolism in the rat. 617 21

Hexobarbital sleeping time was prolonged and ethylmorphine N-demethylation was inhibited after a single dosage or seven administration of 6-SAI to old rats. These effects were independent of the development of arthritis. Changes in cytochrome P-450 concentration after 6-SAI treatment were insignificant and thus not responsible for the decrease in drug metabolism. In vitro 6-SAI inhibited ethylmorphine N-demethylation; the inhibition was of a mixed type. 6-SAI bound to cytochrome P-450 and induced a type II spectrum. The magnitude of hexobarbital-induced type I spectral changes was diminished by 6-SAI. It is concluded that 6-SAI inhibits cytochrome P-450-dependent drug metabolism by binding to cytochrome P-450.
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PMID:Drug metabolism in rats with arthritis induced by 6-sulfanilamidoindazole (6-SAI). 734 Apr 65


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