Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Male rats are fed during twenty eight days from the weaning with semi-synthetic isocaloric diets containing 3,5 p. 100 and 26 p. 100 of proteins under the from of casein and with a standard laboratory diet. At the end of this period the LD50 and the pathological clinical syndrome of a fungicid belonging to the dithiocarbamate series : the Nabame, are determined in each of the groups of rats receiving their respective diet. The LD50 is significantly reduced among the rats with a deficiency in proteins compared with the LD50 determined among the two other groups of animals. A likely explanation is to be looked for, at least for a part, on the level of the production or of the activity of detoxicating microsomal hepatic enzymes which the restrictions of nitrogen supply could reduce. The pathological - clinical syndrome of toxicity : stimulation then depression of the central nervous system, severe inflammation of the gastro-intestinal tract, important renal necrosis, is essentially the same among all the animals and it does not seem to be influenced by the level or nature of the proteinic supply.
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PMID:[Influence of a low-protein diet on the acute toxicity of a pesticide: Nabam]. 101 38

Male Sprague-Dawley rats maintained for a period of 6 or 12 weeks on a basal vitamin E-dificient diet consisting of 70% sucrose, 20% vitamin-free casein, 4% tocopherol stripped lard, 4% salt mixture, and 2% tocopherol-free vitamin fortification mixture were used to compare two sets of commonly used salt mixtures (salt mixtures USP XIV versus Briggs' salt mixture) and two sets of vitamin fortification mixtures (NBC vitamin fortification mixture versus that of Weglicki). Among the rats maintained on the deficient diets for 6 weeks, only those that received the combination of salt mixture USP XIV and vitamin fortification mixture of Weglicki showed a significantly lower level of hepatic catalase activity compared to the corresponding control animals. While there were no significant changes in microsomal cytochromes at this time period, after 12 weeks on the deficient diet, a significant depression in these cytochromes was noted in all experimental groups except the one on salt mixture USP XIV and NBC vitamin fortification mixture. A similar decrease in hepatic catalase was observed in deficient animals at 12 weeks. Since the most striking differences in these diets are in their content of iron and menaquinone, it appears that these two dietary constituents may interact in modulating the effect of vitamin E on hepatic hemeproteins.
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PMID:Effects of different vitamin E-deficient basal diets on hepatic catalase and microsomal cytochromes P-450 and b5 in rats. 118 Feb 43

Naphthylvinylpyridine (NVP) in the cat cerebral cortex (50 mg/kg) and in the mouse brain (100 and 250 mg kg) caused inhibition of choline acetyltransferase (ChA) and didn't influence the acetyl- and butyrilcholinesterase activity and acetylcholine (Ach) content in the mouse brain. NVP (25 mg/kg) failed to influence the ChA activity. Pretreatment with NVP (25 and 250 mg/kg) increased the duration of hexenal sleep in mice greatly, and a dose of 250 mg/kg (but not of 25 mg/kg) enhanced the atropine activity in mice poisoned with armine. NVP (250 mg/kg) reduced the release of Ach from the cerebral cortex of a cat, spontaneous and evoked by atropine and electrical stimulation of the reticular formation of the brain stem. A conclusion was drawn that the pharmacological effect of NVP when the latter was applied in combination with atropine and armine could be connected with the anti-Cha action and the inhibition of the newly-formed Ach, rather than with depression of the microsomal enzymes.
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PMID:[Mechanism of action of naphthylvinylpyridine]. 122 49

The parathion analogue O, O-diethyl, O-phenyl phosphorothionate (SV1) is hepatotoxic when given in large intraperitoneal doses (400 mg/kg body weight) to male rats that have been treated previously with phenobarbitone. The lesion produced at 24 h after dosing is a periacinar hydropic degeneration which appears identical to that caused by carbon disulphide (CS2) in similarly pretreated rats. Both lesions are characterized by a marked depression in hepatic microsomal cytochrome P-450 levels, no change in the concentrations of Na+, K+ and Ca++ in liver water, in contrast to the periacinar necrogenic lesion caused by tccl4 in which Na+ and Ca++ levels markedly increase while that of K+ decreases. The similarity of the SV1 and CS2 induced liver changes, the fact that both chemicals undergo a similar oxidative desulphuration in the liver microsomes and that prior induction of the latter enzymes is necessary in order to produce the injury suggest a similar mechanism for both lesions. A reactive form of sulphur released from the metabolism of CS2 and phosphorothionates in the liver may become covalently bound to constituents of the endoplasmic reticulum of the liver cell and in this way initiate the toxic liver changes. Drugs and chemicals which contain P=S or C=S bonds and which undergo oxidative desulphuration in the liver could thus be similarly hepatotoxic.
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PMID:The hepatotoxicity of O,O-diethyl, O-phenyl phosphorothionate (SV1) for the rat. 126 38

The effects of indomethacin, an inhibitor of prostaglandin synthesis, on rat renomedullary interstitial cells were studied. Indomethacin, 5 mg. per kg. intravenously in divided doses over 48 hours, resulted in reduced granularity of interstitial cells (5.56+/-1.37 versus 9.85+/-1.07 granules per cell, (p is less than 0.001) and, at the same time, inhibited the incorporation of 14C-arachidonate into renomedullary phospholipids (715 + 11 versus 1299 + 42 c.pm.per mug. of lipid orthophosphate; p is less than 0.001) 14C-arachidonate incorporation into cortical phospholipids was not affected by indomethacin. There was a close correlation between individual granule counts and 14C-arachidonate incorporation into medullary phospholipids for both control (r=0.85) and indomethacin-treated animals (r=0.9). Radioactivity in the cytosol fraction was depressed by indomethacin reflecting inhibition of prostaglandin synthesis; cytosol radioactivity correlated closely with individual granule count (r=0.81) in the indomethacin-treated but not in the control rats. Indomethacin given as a single dose 4 hours prior to sacrifice resulted in a significant depression of 14C-arachidonate incorporation but did not affect granularity of interstitial cells. The results suggest that granularity of renomedullary interstitial cells reflects the activity of prostaglandin synthesis and the rate of prostaglandin precursor delivery from microsomal phospholipids.
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PMID:Effects of indomethacin on renomedullary interstitial cells. 127 53

The present investigation provides evidence of the ability of Sn-protoporphyrin to cause striking alterations in adrenal and testicular cytochrome P-450-dependent steroidogenesis and defines the potential of this metalloporphyrin to serve as a cellular toxin. Sn-protoporphyrin is currently used on an experimental basis for treatment of hyperbilirubinemias in humans, including newborn infants. Specifically, in the adrenals of rats treated with a moderate regimen of Sn-protoporphyrin (two doses of 50 mumol/kg, s.c.), marked decreases of 60 to 70% in the microsomal 21 alpha-hydroxylase and the mitochondrial 11 beta-hydroxylase activities were observed after 7 days. Concomitant with these decreases was a significant depression in the adrenal mitochondrial cytochrome P-450 content and a notable reduction (approximately 30%) in serum corticosterone levels. Similarly, in the testes, significant decreases in the microsomal and mitochondrial cytochrome P-450 contents and the microsomal 17 alpha-hydroxylase activity were observed. Serum testosterone level, however, was not decreased, reflecting an absence of decrease in side chain cleavage activity. Metalloporphyrin caused a striking decrease of 65 to 80% in the microsomal heme oxygenase activity in the testes and the adrenals, as well as significant reductions in NADPH-cytochrome P-450 reductase activity of the organs. The decrease in heme oxygenase activity, however, as suggested by Western immunoblotting, apparently resulted, to a large extent, from the loss of enzyme protein integrity rather than a competitive inhibition of activity. At the transcript level, Northern blot analysis using a full length rat testis cDNA probe for heme oxygenase-2 mRNA indicated that Sn-protoporphyrin treatment did not decrease the amount of message for either of the heme oxygenase-2 transcripts (1.3 and 1.9 Kb).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tin-protoporphyrin: a potent inhibitor of hemoprotein-dependent steroidogenesis in rat adrenals and testes. 137 Nov 61

Since the discovery that interferon inducers depress hepatic drug metabolism, the depressant action of cytochrome P450 (P450) has been demonstrated to be shared by cytokines such as interferon alpha/beta and interferon gamma as well as interleukin-1 and tumor necrosis factor. Because these cytokines are inflammatory mediators, it is not surprising that theophylline toxicity has been reported in patients with influenza B epidemic. Hence, to lay a foundation for studies of altered steroid and drug metabolism, the alteration of P450 isozymes was studied after polyriboinosinic acid:polyribocitidylic acid (poly I:poly C) administration. Twenty-four hours after poly I:poly C administration, hepatic P450 content decreased to 57% of control, whereas depression of other microsomal enzymes was less pronounced: P450 reductase (69%), cytochrome b5 (74%) and NADH-cytochrome b5 reductase (85%). The depression of mRNA for cytochrome P450 1A1, 1A2, 2C11 and 2E1 was more than 60% of the controls. Recovery of mRNA levels was not complete within 72 hr. The changes in mRNAs, in general, paralleled alterations of monooxygenase activities and P450 isozyme content suggesting that the effect of poly I:poly C is pretranslational for all P450 isozymes studied. No overt differential effect on P450 isozymes was found after an administration of poly I:poly C. This study complements the previous report which demonstrated down-regulation of mRNA for cytochrome P450 2C11 and 3A2.
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PMID:Suppression of hepatic drug metabolism by the interferon inducer, polyriboinosinic acid:polyribocitidylic acid. 140

Lung cytochrome P-450 has been suggested to play a role in hypoxic pulmonary vasoconstriction. We reexamined this hypothesis using specific suicide substrate inhibitors of cytochrome P-450, 1-aminobenzotriazole (1-ABT), and chloramphenicol. In isolated, blood-perfused rat lungs, 1-ABT (0.5 mg/ml) and chloramphenicol (1 mg/ml) inhibited lung microsomal cytochrome P-450 (ethoxycoumarin O-deethylase) activity to 24 and 44% of control, respectively, and blunted hypoxia and angiotensin II-induced vasoconstriction. The depression of vascular contraction by 1-ABT was not due to an effect on calcium channels, since similar concentrations of 1-ABT had no inhibitory activity on electrical field-stimulated contractile response in rabbit papillary muscle strips. However, when 1-ABT was washed out of the lung after preincubation, the vascular reactivity to hypoxia and angiotensin II was restored despite persistent depression of lung cytochrome P-450 activity to 26% of control values. In isolated rat aortic and pulmonary arterial rings, addition of 1-ABT or metyrapone to the organ bath acutely reversed norepinephrine-induced contraction but preincubation with 1-ABT, metyrapone, or chloramphenicol had no effect on subsequent norepinephrine contractions. We conclude that 1-ABT inhibited lung vascular reactivity by a mechanism independent of cytochrome P-450 inhibition or calcium channel blockade and that an intact lung cytochrome P-450 system is not required for hypoxic pulmonary vasoconstriction in rat lungs.
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PMID:Intact lung cytochrome P-450 is not required for hypoxic pulmonary vasoconstriction. 141 22

Adult male Wistar rats were divided in 3 groups. In the first group, infrarenal abdominal aorta was occluded for 6 hours and reperfused thereafter. In the second group, the reperfusion was not made, and the third group underwent a sham operation. Lysosomal enzymatic activities were assessed in serum tissues. Lysosomal membrane fragilities were estimated also in these tissues. Finally, 14C-aminopyrine breath test (ABT) was studied to define the possible liver dysfunction caused by limb ischemia. As a result, release of lysosomal enzymes from ischemic muscle was confirmed in vitro experiments, and the increase in the serum was statistically significant in the first and second groups as compared to the third group. Particularly prominent was a marked elevation of cathepsin-D in the first group which was observed immediately after the release of occlusion. Results of liver lysosomal enzymes and ABT revealed significant cellular damages and depression of microsomal function of the liver both in the first and second groups. These studies suggest that lysosomal enzymes derived from ischemic muscle exert a possible toxicity on the liver, and liver damage thus resulted may play a roll on the pathogenesis of whole body injury associated with acute and critical lower limb ischemia.
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PMID:[Serum and tissue lysosomal enzymes and liver dysfunction after an experimental acute lower limbs ischemia in the rats]. 144 52

Chronic fatigue syndrome (CFS) includes many symptoms of major depression. For this reason, many antidepressants have been used to treat the symptoms of this disorder. Among the more recently released antidepressants are fluoxetine and bupropion. In this open study, nine CFS patients who either could not tolerate or did not respond to fluoxetine showed significant response when administered 300 mg/day of bupropion for an 8-week period in both rating of HDRS (t = 4.80, p < 0.01) and BDI (t = 2.48, p < 0.05). Furthermore, bupropion improvement in Hamilton Depression Rating Scale correlated significantly with change in plasma homovanillic acid (HVA) (r = 0.96, p < 0.01). Plasma total methylhydroxyphenolglycol (MHPG) also increased significantly during bupropion treatment (t = 2.37, p = 0.05). Measures of T1 microsomal antibodies also decreased over treatment time; increases in natural killer cell numbers correlated inversely with change in plasma levels of free MHPG (r = -0.88, p < 0.05). Bupropion responders were more likely to have trough blood levels above 30 ng/ml (chi 2 = 3.6, p = 0.05).
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PMID:Bupropion treatment of fluoxetine-resistant chronic fatigue syndrome. 145 Feb 97


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