Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The experiments on rats have shown that alpha-tocopherol and lidocaine pretreatment leads to a decrease in the level of ischemic cell necrosis in the liver. The volume of cell necrosis in the liver was significantly decreased (more than threefold) in the case of drug pretreatment. The combination of alpha-tocopherol with lidocaine fully prevented the decrease in N-dimethylation of amidopyrine and cytochrome P-450 and b5 concentration, and the development of destructive alterations of cytoplasmic reticulum in the unaffected rat hepatocytes. alpha-Tocopherol and lidocaine pretreatment was effective for the retention of the depression of microsomal monooxygenases by phenobarbital in remote periods after acute hepatic ischemia.
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PMID:[Prevention, using alpha-tocopherol and lidocaine, of damage to the monooxygenase system activity and ultrastructure of hepatocytes following acute ischemia of the liver]. 368 56

In experiments on rats it was shown that the liver ischemia produces a decrease of the maximal rate of amidopyrine and aniline hydroxylation in microsomes on the 3rd day of the postischemic period. A considerable depth of aniline metabolism inhibition following hepatic ischemia is related to reduced affinity of cytochrome P-450 to substrates of type II. On the 3rd and 14th days of the postischemic period the Michaelis constant and the constant of spectral dissociation for aniline significantly exceeded the given kinetic parameters in control animals. Administration of alpha-tocopherol in combination with lidocaine prevented a decrease of the rate of amidopyrine N-demethylation, the concentrations of cytochromes P-450, b5 and prevented a reduction of cytochrome P-450 affinity to aniline.
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PMID:[Prevention of ischemic damage to the liver monooxygenase system with lidocaine and alpha-tocopherol]. 369 83

Hind-limb ischemia secondary to infrarenal aortic ligation in the rat was evaluated as a traumatic injury model for the study of the effects of trauma on the two major hepatic microsomal drug-oxidizing enzyme systems. Ischemic injury resulted in a significant decrease in hepatic cytochrome P-450 content and FAD-containing monooxygenase activity. Bilateral lower leg fracture was used as a dissimilar traumatic injury model in order to confirm these results and produced similar effects on these enzyme systems. Both forms of injury appeared to be of only moderate severity, and neither injury caused significant histopathological changes in the liver. Moreover, both injuries caused only mild hepatic damage as indicated by relatively modest elevations in glutamic-pyruvic transaminase levels. The observed reductions of cytochrome P-450 content with both forms of model injury were paralleled by decreases in the in vivo metabolism of antipyrine. Thus, it appears that trauma may have a significant, and possibly selective, effect on hepatic drug metabolism, suggesting that careful monitoring and/or dosage adjustment may be in order in some cases of post-traumatic drug therapy. Moreover, the ischemic injury produced by infrarenal aortic ligation in the rat appears to be a suitable small mammal injury model for the further study of the effects of trauma on the various hepatic drug-metabolizing enzyme systems.
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PMID:Effects of model traumatic injury on hepatic drug metabolism in the rat. I. In vivo antipyrine metabolism. 614 Jan 33

A previously validated small mammal trauma model, hind-limb ischemia secondary to infrarenal aortic ligation in the rat, was utilized to further investigate the effects of traumatic injury on hepatic drug metabolism in vivo. The pharmacokinetic sequelae of the previously observed post-traumatic decrease in cytochrome P-450 content were demonstrated, using hexobarbital and zoxazolamine as model cytochrome P-450-oxidized drugs. Sleeping times after ip or iv administration of these drugs was prolonged by model injury. Longer sleeping times appeared to be caused by a slower elimination of the drugs from the bloodstream rather than to an increased sensitivity to their central nervous system effects or to an alteration in plasma protein-binding. Detailed pharmacokinetic analyses by the two-compartmental open system model revealed that the major alteration in post-traumatic drug metabolism was decreased in vivo elimination rather than a shift in distribution. These studies further confirm the pharmacokinetic utility of this convenient small mammal trauma model in the study of post-traumatic derangements in hepatic drug metabolism and emphasize the toxicologic importance of these derangements.
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PMID:Effects of model traumatic injury on hepatic drug metabolism in the rat. II. In vivo metabolism of hexobarbital and zoxazolamine. 614 8

A previously validated small mammal trauma model, hind-limb ischemia secondary to infrarenal aortic ligation in the rat, was utilized to further investigate the effects of traumatic injury on the hepatic cytochromes P-450. In vitro drug metabolism studies with hexobarbital and zoxazolamine as substrates confirmed the post-traumatic depression of the cytochrome P-450-catalyzed oxidation of these drugs which was suggested by previous in vivo pharmacokinetic studies. Enzyme kinetic studies revealed diminished Vmax values with no change in Km, a finding which would seem to concur with the previously demonstrated decrease in hepatic cytochrome P-450 content after model trauma. Moreover, a battery of in vitro microsomal monooxygenase assays demonstrated that model trauma exerted a differential effect on various hepatic cytochrome P-450 isoenzymes. This phenomenon was confirmed by anion-exchange HPLC of solubilized hepatic microsomal hemoproteins. One of the most interesting aspects of this selective effect on cytochrome P-450 subtypes was the relative induction of cytochrome P-448 content and activity, in contrast to the variable decrease seen with cytochrome P-450 activities. The potential in vivo sequelae of this differential influence were suggested by changes observed in the urinary metabolic profile of antipyrine after model trauma.
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PMID:Effects of model traumatic injury on hepatic drug metabolism in the rat. III. Differential responses of cytochrome P-450 subpopulations. 614 9

One-hour ischemia followed by rat liver reoxygenation brings about the accumulation of endogenous products of lipid peroxidation (LPO) and deterioration of the monooxygenase system (the drop of cytochrome P-450 content, amidopyrine N-demethylase and NADP X H cytochrome reductase activity). Application of the antioxidant ionol inhibited LPO and protected the monooxygenase system from reoxygenation but not from ischemic injuries. Phenobarbital alone and combined with ionol did not protect the monooxygenase system from ischemic and reoxygenation injuries but provided the retention of high absolute indicators of the system. Ionol and its combination with phenobarbital also increased the survival of rats with ischemized liver.
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PMID:[Protective action of antioxidants and microsomal monooxygenase inducers in ischemic and reoxygenation damage to the liver]. 683 Oct 14

If 60 min long ischemia of a liver tissue lobe occurred after feeding of rats with oil emulsion of alpha-tocopherol at a dose of 50 mg/kg within 12 hrs during 2 days, the "ischemic" decrease in metabolism of amidopyrine and aniline, in content of cytochrome P-450 and activity of initial and middle steps of NADPH-dependent redox chain as well as intensification of ascorbate-dependent peroxidation of membrane lipids were prevented in endoplasmic reticulum of hepatocytes. The protective effect of alpha-tocopherol on these xenobiotics metabolism is apparently related to an increase in catalytic activity of cytochrome P-450, to the enzyme antioxidant and membrane-stabilizing properties.
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PMID:[Effect of alpha-tocopherol on the hydroxylating system and lipid peroxidation in membranes of endoplasmic reticulum from ischemic rat liver]. 683 66

Local disturbance of liver circulation for 40 minutes did not lead to any substantial changes in the hydroxylation system of microsomes of the ischemized area. 60-, 120- and 180-minute circulation distress causes a progressing decrease in amidopyrine and aniline metabolism, diminution of the content of cytochrome P-450 in the microsomes, and of the activity of NADP.H-ferricytochrome-c-reductase, NADP.H-neotetrazolium-reductase and NADP.H-oxidase. After 120-minute ischemia hydrophobic properties of the microsomal membranes were found to be decreased.
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PMID:[Changes in the enzyme activity of the hydroxylating system of the rat liver endoplasmic reticulum in ischemia]. 705 83

The content of endogenous lipid peroxidation products and variations in mixed function oxygenases were examined in liver microsomes of rats exposed to thermal ischemia of varying duration (15, 30, 60 and 120 min). The development of ischemic injury was accompanied by the accumulation of lipid hydroperoxides and Schiff's base, by the lowering of the content of cytochrome P-450 and diminution of the activity of NADPH-cytochrome P-450 reductase. The maximum changes were demonstrated 2 hours after ischemia. The presence of a reverse correlation between the content of lipid peroxidation products and the content of cytochrome P-450 was recorded.
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PMID:[Lipid peroxidation and damage to the mixed function oxidase system in membranes of the endoplasmic reticulum in the presence of liver ischemia]. 729 45

Presently we describe, for the first time, induction of microsomal heme oxygenase-1 (HO-1) mRNA and protein in response to ischemia/reperfusion and therefore define HO-1 as stress protein in the kidney. Specifically, Northern blot analysis of kidneys of rats subjected to bilateral ischemia for 30 min revealed an increase of 8- to 10-fold in the level of 1.8 Kb HO-1 mRNA 6 hr after reperfusion. The increase in transcript level was maintained when assessed after 24 hr. The levels of 1.3 and 1.9 Kb transcripts for the second isozyme of HO, HO-2, were decreased at both time points. The increase in HO-1 mRNA was reflected in HO-1 protein level, as judged by Western blot analysis and at the level of activity as judged by the rate of bilirubin formation. An absence of change in adrenal HO-1 mRNA level subsequent to renal ischemia/reperfusion suggested that the induction of kidney HO-1 did not reflect a generalized response of the rat organs to stress; rather, it was a target organ specific response. Moreover, in kidneys subjected to ischemia 6 and 24 hr after reperfusion, significant increases in the cellular content of heme were observed; heme is a known inducer of HO-1 synthesis. Ischemia/reperfusion also adversely affected concentration of cytochrome P-450 in both mitochondrial and the microsomal fractions of the kidney. We suggest that increase in tissue heme levels may be a significant factor in damage caused by ischemia/reperfusion to renal tissue, whereby the metalloporphyrin promotes oxygen-free radical formation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Induction of kidney heme oxygenase-1 (HSP32) mRNA and protein by ischemia/reperfusion: possible role of heme as both promotor of tissue damage and regulator of HSP32. 842 44


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