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

We studied the effect of dietary lipids on iron metabolism and lipid peroxidation during induced adjuvant arthritis and/or iron overload in rats. We compared a control diet containing corn oil and rapeseed oil with a diet devoid of polyunsaturated fatty acids containing only tripalmitin as lipids. Four subgroups of rats were used with each diet: without further treatment, with induction of adjuvant arthritis, with iron overload, and with induction of adjuvant arthritis and iron overload. The profile of fatty acids present in plasma and in microsomes changed in rats fed the tripalmitin diet. The level of tetra- and pentaunsaturated fatty acids was reduced, and the level of monounsaturated fatty acids and iron stores was increased with respect to control rats. Thus, ingestion of a tripalmitin diet reduced the substrate for lipid peroxidation, as shown by the decrease in thiobarbituric acid-reactive substances in plasma and conjugated dienes in hepatic microsomal fraction. Adjuvant arthritis and iron overload had a synergistic effect on lipid peroxidation and iron storage in liver. Further, in the hepatic microsomal fraction, tripalmitin reduced the levels of cytochrome P-450, and arthritis reduced the levels of cytochrome P-450 and Ca2+ sequestration. Our results suggest that rats fed tripalmitin showed a reduction of lipid peroxidation induced by inflammation or by iron overload, because of the lack of polyunsaturated fatty acids in the diet, although tripalmitin usually increases the iron stores in the body and causes hepatic alterations.
 ...
PMID:Dietary lipid and iron status modulate lipid peroxidation in rats with induced adjuvant arthritis. 761 10

A relationship between the production of interleukin 1 (IL-1) by macrophages from adjuvant-induced arthritic rats and cytochrome P-450-dependent hepatic microsomal monooxygenase was studied. The synthesis of IL-1 by splenic and peritoneal macrophages on day 17 postadjuvant treatment was not altered, but the hepatic cytochrome P-450 levels and monooxygenase activity were significantly decreased. Beta-carotene treatment of arthritic rats reduced hind paw swelling and concurrently stimulated the ability of macrophages to secrete IL-1 and increased the cytochrome P-450 levels and the activity of hepatic monooxygenase. The findings did not establish a definite relationship between the production of IL-1 by systemic macrophages on the one hand, and the hepatic cytochrome P-450 levels a and monooxygenase activity on the other hand. It thus appears that IL1 is unable to play a role of a mediator between the immune system and the hepatic cytochrome P-450-dependent monooxygenase system of rats with adjuvant-induced arthritis.
 ...
PMID:[The cytochrome P-450-dependent mono-oxygenase system of the liver and interleukin-1 production by the macrophages in adjuvant arthritis in rats under the influence of beta-carotene]. 778 97

Experimental arthritis and inflammation have been reported to reduce liver cytochrome P-450-dependent mono-oxygenase activities with subsequent impairment of drug metabolism. Interleukin-1 beta (IL-1) is among the proven mediators of both inflammation and P-450 decrease, although some paradoxical effects were sometimes reported in experimental models of arthritis. The aim of the present study was to evaluate the main liver drug-metabolizing isoenzymes during established collagen-induced arthritis in rats, and to investigate whether a systemic IL-1 treatment was able to mimic or sometimes to reverse the influence of the inflammatory process on these enzymes. Arthritis was induced on day 0 by type II collagen and a low dose (0.2 mg) of N-acetylmuramyl-L-alanyl-D-isoglutamine, and human recombinant IL-1 was administered s.c. at the daily dose of 0.02, 0.2 or 2.0 micrograms per arthritic rat, from day 21 to 25 and on day 28. Ethoxyresorufin-O-deethylation was depressed 6-fold in arthritic rat liver microsomes and the highest dosage of IL-1 potentiated this depression. Pentoxyresorufin-O-deethylation decreased by 50% in arthritic rat, a dose-dependent decrease being observed after IL-1 treatment. Progesterone 6 beta-hydroxylation and P-450 IIIA protein increased by 2-fold in both untreated arthritic rat liver microsomes and those treated by the lowest dose of IL-1. The two higher doses decreased this activity, vs. the dose, to reach the naive level. Lauric acid hydroxylation increased 2-fold in arthritic rat and was further potentiated by IL-1. UDP glucuronosyl transferase IA2 activity was increased 2-fold in arthritic rats, with subsequent decrease after 2.0 micrograms of IL-1.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Interleukin-1 beta differentially represses drug-metabolizing enzymes in arthritic female rats. 843 2

The effect of adjuvant-induced arthritis on hepatic microsomal glucuronidation was studied in the rat. Arthritis was induced by injection of Mycobacterium butyricum suspended in liquid paraffin. Vmax and the Michaelis-Menten constant values for the in vitro glucuronidation of R- and S-ketoprofen, acetaminophen, and diflunisal by liver microsomes obtained from control and adjuvant-induced arthritic rats were compared. In addition, uridine 5'-diphosphate-glucuronosyltransferase activity toward bilirubin and p-nitrophenol, as well as levels of cytochrome P-450 and beta-glucuronidase were determined in these microsomal preparations. Adjuvant-induced arthritis resulted in a significant reduction in hepatic cytochrome P-450 levels and in p-nitrophenol glucuronidation (5.65 +/- 0.40 versus 2.58 +/- 0.27 micromol.min/mg protein in control and arthritic rats, respectively, mean +/- S.E.M.). Glucuronidation of bilirubin and beta-glucuronidase activities in liver microsomes and in plasma were not affected by adjuvant-induced arthritis. Vmax (nmol/min/mg protein) for the formation of R-ketoprofen glucuronide, S-ketoprofen glucuronide, diflunisal phenolic glucuronide, and diflunisal acyl glucuronide was significantly decreased in arthritic rats (0.68 +/- 0.10, 0.77 +/- 0. 12, 0.044 +/- 0.005, 0.26 +/- 0.03, respectively) compared with control rats (1.45 +/- 0.04, 1.60 +/- 0.04, 0.087 +/- 0.008, 0.46 +/- 0.04, respectively). Glucuronidation of p-nitrophenol, ketoprofen and diflunisal, substrates which seem to be at least partly glucuronidated in the rat by isoenzymes of the UGT2B subfamily, was impaired in adjuvant-induced arthritis. Glucuronidation of bilirubin and acetaminophen, substrates of UGT1- isoenzymes, was not affected by adjuvant-induced arthritis. It seems, therefore, that adjuvant-induced arthritis in the rat leads to impaired glucuronidation of substrates of the UGT2B subfamily.
 ...
PMID:Glucuronidation of R- and S-ketoprofen, acetaminophen, and diflunisal by liver microsomes of adjuvant-induced arthritic rats. 988 6


<< Previous 1 2