Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.6.99.3 (diaphorase)
 5,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interferon and its inducers are known to depress drug biotransformation in vivo by decreasing the levels of cytochrome P-450 (P450) monooxygenase system in the liver. However, very little is known about the effects of interferon on P450 in extrahepatic tissues. In this study we investigated the effects of a recombinant human interferon-alpha (rhIFN-alpha) on aryl hydrocarbon hydroxylase (P450IAI) in cultured human peripheral lymphocytes (HPL). Non-induced and induced (3-methylcholanthrene) mitogen activated lymphocytes were used throughout the study. rhIFN-alpha maximally depressed AHH activity to approximately 58% of control after 24 hrs of incubation in both non-induced and induced lymphocytes. However, after 48 hrs of incubation with rhIFN-alpha, AHH activity had recovered to 86% of control in induced cells and 61% in non-induced cells. rhIFN-alpha had no significant effect on either NADH cytochrome c reductase activity or on viable lymphocyte cell count. This is the first demonstration that rhIFN-alpha can have a direct depressive effect on a P450 dependent monooxygenase system in HPL.
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PMID:Effects of recombinant human interferon alpha on aryl hydrocarbon hydroxylase activity in cultured human peripheral lymphocytes. 202 Feb 55

We have investigated a relationship between two detoxication systems, metabolic detoxication through the cytochrome P-450 (P-450) pathway and resistance to infection through interferon (IFN), in mice infected with influenza virus following exposure to coal dust (CD) and diesel exhaust (DE) particulates. Mice were exposed by inhalation to filtered air (FA; control), CD, or DE for 1 month and then inoculated intranasally (IN) with influenza virus. During infection, 7-ethoxycoumarin deethylase (7ECdeEt'ase) and ethylmorphine demethylase (EMdeMe'ase) (monooxygenases), and NADPH cytochrome c reductase (NADPH c red'ase) were measured in liver microsomes. Temporal patterns of enzyme activities were observed with control animals. EMdeMe'ase and NADPH c red'ase exhibited peak values at Day 4 postinfection (27.6 and 482 nmole/min/mg protein, respectively), compared to initial activities (9.1 and 307 nmole/min/mg protein, respectively). 7ECdeEt'ase activity decreased between Days 1-3 postvirus infection and thereafter returned to the original value (1.7 nmole/min/mg protein). When the mice were first exposed to CD or DE particulates for 1 month prior to influenza infection, changes in enzyme temporal patterns were observed. The increased EMdeMe'ase activity at Day 4 was not observed in mice exposed to CD and was reduced in mice exposed to DE. Preexposure to either particulate resulted in the abolition of the increased Day 4 activity of NADPH c red'ase. The 7ECdeEt'ase postinfection temporal pattern was not affected by a preexposure to either particulate. Estimates of the enzyme activities after the 1-month exposure to FA, CD, or DE but before virus infection indicated no changes due to particulate exposure alone. Under these conditions of particulate exposure and virus infection, serum IFN levels in the mice used in this study peaked at Days 4-5 and were unaffected by the 1-month preexposure to CD or DE (Hahon et al., (1985). The data suggest the relationship that exists between metabolic detoxication and resistance to infection in normal mice was altered during a short-term preexposure to CD or DE.
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PMID:Influenza virus-induced alterations of cytochrome P-450 enzyme activities following exposure of mice to coal and diesel particulates. 242 23

Treatment of mice and rats with polyriboinosinic acid-polyribocytidylic acid (poly I.C., 5 mg/kg i.p.), a potent interferon inducer, decreased hepatic cytochrome P-450 system content and activities without influencing P-450-independent xenobiotic metabolizing enzymes. Treatment with poly I.C. decreased the content of P-450 by 28% in mice (P less than 0.05) and 30% in rats (P less than 0.05) but did not alter the activity of cytochrome c reductase. With treatment of poly I.C., the activity of XO increased 87% in mice (P less than 0.01) and 30% in rats (P less than 0.01). Lipid peroxidation was enhanced by 82% in mice (P less than 0.01) and 95% in rats (P less than 0.05). These results raise the possibility that a part of the depression of P-450 system content and activities by poly I.C. might be caused by enhanced lipid peroxidation associated with increased activity of XO.
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PMID:Treatment with poly I.C. enhances lipid peroxidation and the activity of xanthine oxidase, and decreases hepatic P-450 content and activities in mice and rats. 375 66

Interferon inducers, poly I:poly C, endotoxin, hepatic RNA, and Tilorone, were administered to rats at different time points in relation to the onset of hyperoxic exposure (O2 greater than 97%). All interferon inducers tested significantly reduced the mortality of rats when compared with the control groups. In hyperoxia alone, malondialdehyde, a product of lipid peroxidation, was significantly increased and the microsomal enzyme NADPH cytochrome c reductase decreased as measured in the whole lung. With the administration of either endotoxin or poly I:poly C these two parameters remained within the range of control values. These data suggest that the administration of interferon inducers protects against hyperoxic microsomal damage. After the administration of these interferon inducers with or without hyperoxia the increased activity of heme oxygenase and marked reduction of the heme content of microsomes were demonstrated. Since cytochrome P-450 and b5 are the major hemoproteins of microsomes and the known source of oxygen-free radical generation, the results obtained in this study appear to indicate that the depression of the hemoprotein of microsomes by the administration of interferon inducers may be largely responsible for the protective effects of these agents against hyperoxia.
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PMID:Protective effect of interferon inducers against hyperoxic pulmonary damage. 654 2

A lambda cDNA library prepared from polyadenylated RNA isolated from Daudi cells was differentially screened to isolate cDNAs that recognize mRNA whose levels are reduced following interferon (IFN) treatment. Southern blot and DNA sequence analysis of 20 cDNA clones that were isolated revealed that they represented mitochondrially encoded mRNAs for the following proteins: cytochrome c oxidase subunits II and III, ATPase 6, cytochrome b, and subunit 1 of the NADH dehydrogenase. Northern blot analysis employing these cDNAs and oligonucleotides generated to the remaining mitochondrially encoded mRNAs demonstrated that IFN-alpha treatment of Daudi cells mediates a time-dependent suppression of the level of all of the mitochondrially encoded mRNAs. Study of this IFN-mediated effect reveals that: (i) the suppression of the level of these mRNAs is dependent on protein synthesis, (ii) it can be observed to occur prior to any detectable effect on thymidine incorporation, (iii) the degree of suppression correlates with the sensitivity of the cells to the anticellular action of IFN, and (iv) the suppression of the level of these RNAs appears to result from an effect on the level of transcription rather than on the stability of these mRNAs. A study of the level of cellular respiration in IFN-treated Daudi cells reveals a clear suppression 3 h following IFN treatment.
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PMID:Suppression of mitochondrial mRNA levels and mitochondrial function in cells responding to the anticellular action of interferon. 751 85

We showed previously that type I interferon causes a down-regulation of mitochondrial gene expression. We show here that IFN treatment leads to functional impairment of mitochondria. Western blot analysis indicated that interferon treatment reduces the steady-state level of cytochrome b in murine L-929 cells. Interferon produced a reduction in cytochrome c oxidase and NADH-cytochrome c reductase activities of isolated mitochondria as well as inhibiting electron transport in isolated mitochondria and in intact cells. Several mitochondrial mRNAs are affected by interferon treatment in human Daudi lymphoblastoid cells, which are highly sensitive to the antiproliferative effects of interferon. Electron transport in Daudi cells was also inhibited by interferon both in intact cells and isolated mitochondria with a dose response identical to that for the antiproliferative response. In contrast, a Daudi strain resistant to the antiproliferative effects of interferon showed no down-regulation of mRNA expression and no inhibition of electron transport. Possibly as a consequence of the inhibitory effect on mitochondrial gene expression, treatment with interferon causes a reduction in cellular ATP levels. The inhibition of cellular growth by interferon may thus be partly a consequence of a reduction in cellular ATP levels.
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PMID:Inhibition of mitochondrial function by interferon. 866 94

Effect of 6-MFA (sixth mycelial fraction of acetone), an interferon inducer obtained from fungus A. ochraceus on hepatic mixed function oxidase system (MFO) of rat has been investigated. Treatment with 6-MFA, 100 mg/kg/day, ip for 1-5 days to adult rats inhibited significantly the different indices of MFO system, viz. hepatic cytochrome P-450, cytochrome b5 content, cytochrome c reductase, aminopyrine-N-demethylase and acetanilide hydroxylase activities. Similar treatment for 3 days in young growing rats significantly inhibited MFO system's components except acetanilide hydroxylase activity which showed marked elevation. These effects seem to be specific as in vitro experiments suggested that 6-MFA does not compete with subsdtrates nor it acts as a sponge reacting with the end product to give false inhibitory effect. It is concluded from the present study that 6-MFA like other interferon inducers depresses MFO system in rats. Its possible clinical implications are discussed.
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PMID:Effect of 6-MFA, an interferon inducer obtained from fungus Aspergillus ochraceus on hepatic mixed function oxidase system in rats. 905 55

Clinicopathogenetic impact of cycloferon, an endogenous interferon inductor, on the process of Astrakhan rikettsial fever, its complications and outcomes was analysed. The treatment scheme with addition of cycloferon to the complex therapy was optimized. The specificity of the disease clinical process and the level of the interferon status in the patients treated with cycloferon alone or with combination of the standard therapy and cycloferon was shown. It was observed that in the patients with moderate severity of the disease the combined use of the standard therapy and cycloferon was in favour of arresting the disease clinical signs (fever, headache, weakness, eruption, hepatomegaly, arthralgia and myalgia, lymphatic gland inflammation, primary affect) and lowered the hospitalization term vs. the standard therapy alone. In the patients with moderate severity of the disease the levels of the serous interferon-alpha before the treatment were found lower, while those of interferon-gamma were higher. The use of cycloferon in the treatment scheme resulted in increase of the interferon-alpha levels and decrease of the higher levels of interferon-gamma. The standard therapy in combination with cycloferon in the patients with moderate severity of the disease provided changes in the immune status: increase of the relative content of T- and B-lymphocytes and normalization of their absolute number. Normalization of the phagocytic activity and the coefficient of the active phagocytes, as well as increase of the phagocytic index, the levels of immunoglobulins G, A and M and the number of the circulating immune cells were stated. The standard therapy with addition of cycloferon resulted in normalization of the levels not only of succinic denydrogenase, lactate dehydrogenase and glucose-6-dehydrogenase but also of alpha-naphthylacetate esterase and alpha-naphthylbutirate esterase in the neutrophils, as well as of the whole spectrum of the monocyte enzymes, except NAD-diaphorase. The adverse reactions were observed in 2.5% of the cases (9 subjects). All of them were mild and did not require discontinuation of the drugs use.
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PMID:[Evaluation of safety and pharmacotherapeutic efficacy of cycloferon in treatment of Astrakhan rickettsial fever]. 2274 Nov 99