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)

Dexamethasone acetate (100 microgram IP) protected male Holtzman rats (300-330 gm) against endotoxin shock due to Salmonella enteritidis lipopoly-saccharide B IV. Endotoxin (5.0 mg/rat) produced hypoglycemia within 180 minutes, ie, plasma glucose fell from 87 to 24 mg/dl; dexamethasone prevented the hypoglycemia, ie, plasma glucose levels were 129 mg/dl at 180 minutes after endotoxin. Dexamethasone antagonized both endotoxin-induced depression of hepatic gluconeogenesis and enhanced glucose oxidation as evaluated in vivo. Epididymal fat pads from endotoxic rats (100-110 gm) had increased rates of glucose oxidation as evaluated by the in vitro conversion of 14C-D-glucose to 14CO2. Dexamethasone both in vivo and in vitro antagonized endotoxin glucose hypercatabolism by isolated epididymal fat pads following administrated of endotoxin. Glucocorticoid protection against endotoxin shock is related to antagonism of glucose dyshomeostasis.
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PMID:Dexamethasone antagonism of glucose dyshomeostasis in endotoxin shock. 28 Apr 23

ATP-Mg++ (10 mumoles/100 g, iv) increased the LD50 for Salmonella enteritidis lipopolysaccharide (endotoxin) in male Holtzman rats (300 +/- 10 g) from 1.3 to 6.0 mg/rat. While endotoxin at 3 mg/rat iv 5 hr previously induced hypoglycemia to 12 +/- 4 mg/dl, ATP cotreatment blunted the hypoglycemia; i.e., plasma glucose values were 78 +/- 6 mg/dl. ATP treatment prevented the depression in gluconeogenesis induced by endotoxin as evaluated in vivo by the conversion of 14C-alanine to 14C-glucose. ATP treatment also reduced the hypercatabolism of U-14 C-glucose to 14CO2 in vivo and by epididymal fat pads in vitro. A role for ATP in preventing disruption of glucose homeostasis and development of endotoxin shock via counteracting insulin is suggested.
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PMID:Protection against endotoxin shock and impaired glucose homeostasis with ATP. 33 38

7-oxa-13-prostynoic acid (OPA) and polyphloretin phosphate (PPP) are believed to act as specific antagonists of prostaglandin action. In order to estimate their specificity, the inhibitory effects of these drugs were tested on the activity of adenylate cyclase from several tissues which were stimulated by prostaglandins and several other compounds. In adenylate cyclase preparation from L-fibroblasts both OPA (0.15-1.5 MM) and PPP (0.01-1.0 MG/ML) antagonized not only the stimulatory effects of PGE but also the stimulatory effects of sodium fluoride and increased enzyme activity due to the previous treatment of cell cultures by cholera toxin. Both OPA and PPP produced a dose dependent depression of adenylate cyclase activity to zero values both under basal conditions and after stimulation by sodium fluoride and various hormones in all preparations studied, including rat liver, heart, brain, epididymal adipose tissue, small intestine, renal cortex and renal medulla. The present results indicate that both prostaglandin antagonists may, in higher concentrations, act as nonspecific inhibitors of the catalytic unit of adenylate cyclase rather than specific antagonists of the prostaglandin effects on adenylate cyclase.
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PMID:7-oxa-13-prostynoic acid and polyphloretin phosphate as non-specific antagonists of the stimulatory effects of different agents on adenylate cyclase from various tissues. 123 93

The effects on the fertility of adult male rats of six new synthetic steroids: I, 3-cyano-5alpha-androst-1-en-17-one; II, the 17beta-acetate form of I; III, 17beta-hydroxy-5beta-cyano-androstan-3-one; IV, 6-methylpregnenolone; V, 17beta-hydroxy-17alpha-ethynyl-5beta-cyano-19-norandrostan-3-one; and VI, 19-norspiroxenone (oestr-4-en-3-one-spiro-17alpha-2'-[tetrahydrofuran]) have been tested. After 6 weeks of treatment with daily doses of 5 mg (I, II, III), 15 mg (IV) or 10 mg (V, VI) only steroid VI blocked the completion of spermatogenesis and reduced the number of foetuses sired in at least five females/male. Steroid VI also diminished seminal vesicular, prostatic, testicular and epididymal weights. It inhibited the testicular enzymes, 3beta-hydroxysteroid dehydrogenase-delta4-5-3-oxosteroid isomerase system, 17alpha-hydroxylase, and C17-20 lyase markedly, but did not affect the adrenal dehydrogenase-isomerase system. It depressed, strikingly, testicular and serum levels of testosterone and 5alpha-dihydrotestosterone and reduced pituitary and serum levels of FSH and LH. Although marked depression of target organ weights also occurred with steroids II, IV and V, and reduction of androgen levels and LH in the circulation with III, IV and V, only VI was a potent blocker of male fertility with the exception of a slight block of the siring of viable foetuses by steroids IV and V. The major difference in site of action of steroid VI from the others was the depression of pituitary and serum levels of FSH along with a marked diminution of testicular content of both testosterone and 5alpha-dihydrotestosterone. 19-Norspiroxenone in the rat is a potent anti-oestrogen without inherent oestrogenicity and is anti-uterotrophic. Thus, VI may affect male fertility by virtue of its potent anti-oestrogenic action in the hypothalamus or testis.
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PMID:Effects of new multi-site hormone blockers on the fertility of male rats. 127 Sep 48

The objective of this investigation was to characterize the acute and short- and long-term toxic potency of orally administered 1,2-dichloropropane (DCP). In the acute and short-term studies, male rats of 250-300 g were gavaged with 0, 100, 250, 500, or 1000 mg DCP/kg in corn oil once daily for up to 10 consecutive days. Although ingestion of DCP caused body weight loss and CNS depression, few other toxic effects were manifest 24 hr after a single dose of the chemical. Morphological changes were limited to liver centrilobular cells in 500 and 1000 mg/kg rats. Similarly, elevated activity of some serum enzymes occurred only at these two highest dose levels. Hepatic nonprotein sulfhydryl (NPS) levels were decreased and renal NPS levels increased at 24 hr. In the short-term study resistance developed to DCP hepatotoxicity over the 10 consecutive days of exposure, as reflected by progressively lower serum enzyme levels and by decreases in the severity and incidence of toxic hepatitis and periportal vacuolization. Nucleolar enlargement in hepatocytes, however, was observed at all dosage levels at 5 and 10 days. There were a number of manifestations of hemolytic anemia, including erythrophagocytosis in the liver, splenic hemosiderosis and hyperplasia of erythropoietic elements of the red pulp, renal tubular cell hemosiderosis, and hyperbilirubinemia. Urinalyses and histopathology revealed no evidence of nephrotoxicity. In the long-term study, male rats initially weighing 180-200 g were gavaged five times weekly for up to 13 weeks with 0, 100, 250, 500, or 750 mg DCP/kg. As over one-half the 750 mg/kg group died within 10 days, the survivors were sacrificed. Histopathological changes in the 750 mg/kg animals included mild hepatitis and splenic hemosiderosis, as well as adrenal medullary vacuolization and cortical lipidosis, testicular degeneration and a reduction in sperm, and increased number of degenerate spermatogonia in the epididymis in some members of the group. Similar testicular and epididymal degenerative change also were observed in some 500 mg/kg animals after 13 weeks of dosing. There was a progressive increase in the number of deaths in the 500 mg/kg group, such that more than 50% were dead by 13 weeks. No deaths occurred in the 100 or 250 mg/kg groups. The DCP dosage regimen also produced a dose-dependent decrease in body weight gain. DCP exhibited very limited hepatotoxic potential and no apparent nephrotoxic potential in the long-term study. Slight elevations in serum ornithine-carbamyltransferase activity, periportal vacuolization, and active fibroplasia in the liver were seen in the 500 mg/kg animals.
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PMID:Oral toxicity of 1,2-dichloropropane: acute, short-term, and long-term studies in rats. 274 74

The inhibitory effects of atropine and pirenzepine (nonselective and M1-selective antagonists, respectively) on the contractile responses of the epididymal half of the rat vas deferens to methacholine included a depression of the maximal response. In the presence of pirenzepine, atropine was a competitive antagonist of the responses to methacholine. However in the presence of atropine, pirenzepine remained a non-competitive inhibitor of the response. It is suggested that low concentrations of methacholine predominantly stimulate M2-receptors and that at high concentrations, methacholine also stimulates M1-receptors.
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PMID:M1 and M2-muscarinic receptors in the epididymal half of the rat vas deferens. 375 24

1. The effect of dinitrophenol on the metabolism of glucose labelled with (14)C and tritium by epididymal fat-pad segments from fed rats was studied. Dinitrophenol at concentrations of 0.1-0.3mm: (a) had little effect on glucose utilization; (b) depressed synthesis of fatty acids and greatly increased that of lactate; (c) increased the T/(14)C ratio in fatty acids synthesized from [U-(14)C,3-T]glucose and decreased that in fatty acids synthesized from [U-(14)C,4-T]glucose; (d) abolished randomization of (14)C from [6-(14)C]glucose in lactate. 2. Dinitrophenol stimulated oxidation of pyruvate and greatly inhibited the oxidation of lactate. It inhibited lipogenesis from pyruvate and lactate. 3. From the isotope data it was calculated that: (a) dinitrophenol stimulates oxidation via the tricarboxylic acid cycle three- to six-fold; (b) dinitrophenol depresses markedly the operation of the pentose cycle; (c) in the presence of dinitrophenol, NADPH formed in the pentose cycle provides all the hydrogen equivalents for fatty acid reduction, whereas, in its absence, NADPH provides 50-70% of the hydrogen equivalents; (d) in the presence of dinitrophenol, there is an excess of ATP produced in the cytoplasm, which flows into the mitochondria. A reverse flow operates in the absence of dinitrophenol. 4. A balance of formation and utilization of reduced nicotinamide nucleotides in the cytoplasm was established. With dinitrophenol there is some excess of NADH. There are indications that this excess may be transferred into mitochondria in the form of malate. 5. Our results are interpreted to indicate the absence from adipose tissue of the alpha-glycerophosphate shuttle for transferring reducing equivalents from the cytoplasm to mitochondria. 6. The effects of dinitrophenol are accounted for in terms of decreased ATP concentrations in the cells, leading to marked decrease in pyruvate carboxylation in the mitochondria and depression of fatty acid synthesis in the cytoplasm.
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PMID:The effect of 2,4-dinitrophenol on adipose-tissue metabolism. 438 39

We have compared the effects of cellular cyclic AMP modulation on the regulation of lipoprotein lipase in cultures of rat epididymal pad preadipocytes and mesenchymal heart cells. Addition of dibutyryl cyclic AMP (dibutyryl cAMP) or 3-isobutyl-1-methylxanthine (IBMX) to preadipocytes grown in serum-containing culture medium resulted in a progressive decrease in lipoprotein lipase activity released into the culture medium so that at 6-8 h enzyme activity ranged between 20 and 30% of that recovered in the control dishes. Similar short-term (6-8 h) studies of the heart cell cultures showed a variable and much less pronounced depression of lipoprotein lipase activity. Thus, following dibutyryl cAMP and IBMX treatment, lipoprotein lipase activity ranged between 70 and 95% of control values. Incubation for 6 h with cholera toxin was followed by a 4-fold rise in the concentration of cellular cyclic AMP in both types of culture, but while in heart cell cultures enzyme activity was unchanged, lipoprotein lipase activity in preadipocytes decreased to 30% of control value. After 24 h incubation with all three effectors, an increase in lipoprotein lipase activity was seen. In the preadipocytes the increase ranged between 50 and 150% above control value, in the heart cell cultures it was 100-250%. 24-h incubation of heart cell cultures with dibutyryl cAMP resulted in a 6-fold increase of heparin-releasable lipoprotein lipase activity while residual activity was doubled. The rise in surface-bound lipoprotein lipase was evidenced also by an increase in the lipolysis of chylomicron triacylglycerol. In the presence of cycloheximide, the dibutyryl cAMP-induced heparin-releasable and residual lipoprotein lipase activity declined at the same rate as the basal activity. The reason for the difference in response of cultured preadipocytes and heart cells to the effectors during the first 8 h of incubation has not been elucidated, but could be related to a possible absence of hormone-sensitive lipase in the heart cells, and hence in a difference in intracellular metabolism of triacylglycerol. On the other hand, a common mechanism can be postulated for the long-term effect of cyclic AMP on the induction of lipoprotein lipase activity in both types of cultures. It probably involves mRNA and protein synthesis, which culminates in an increase in enzyme activity.
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PMID:Modulation of lipoprotein lipase activity in cultured rat mesenchymal heart cells and preadipocytes by dibutyryl cyclic AMP, cholera toxin and 3-isobutyl-1-methylxanthine. 618 19

Insulin-effects on adenylate cyclase activity, cyclic AMP (cAMP) content and free fatty acid (FFA) accumulation of rat epididymal fat cells were examined under conditions of maximal inhibition of phosphodiesterase by sufficient amounts of theophylline for the purpose of localizing the site of the antilipolytic action of insulin. After brief preincubation of the cells with physiological amounts of insulin in the presence or absence of 0.1 mM adrenalineee, fat cells were homogenized following the addition of theophylline and then further incubated. Under these conditions, small but significant enhancement of adenylate cyclase activity, cAMP content and FFA accumulation by insulin alone was observed, while insulin remarkably inhibited adrenalin-stimulated FFA accumulation, reducing adenylate cyclase activity and cAMP levels. This increase of cAMP content by insulin was only seen 5 or 15 minutes after the addition of theophylline. Furthermore, this insulin effect was also observed in the experiments which were performed in a medium containing high concentrations of albumin (2%). The concomitant accumulation of FFA might have resulted from the stimulation of lipolysis, rather than from the synthesis of FFA, since there was no added glucose in the medium. And finally, the hydrolysis of 14C-tripalmitate by a fraction of the cell homogenate under the presence of theophylline was more extensive after preincubation of the cells with insulin than without insulin. In summary, insulin, which is recognized as a typical antilipolytic hormone, activated adenylate cyclase and increased lipolysis at its physiological concentrations when it alone exerted its effect upon fat cells under the conditions where phosphodiesterase was completely inhibited by theophylline. Accordingly, the present results indicate the bimodal effect of insulin on adenylate cyclase and lipolysis under the presence of theophylline; enhancement when applied alone, and depression with adrenalin. So it is most likely that the "negative synergism" occurs as a net effect when a mild activator acts together competitively with a strong activator toward the same target. These data suggest the fundamental roles of adenylate cyclase systems in the mechanism of lipolysis regulation by insulin.
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PMID:[Insulin action on adenylate cyclase. The effect of insulin on adenylate cyclase of rat fat cells in the presence of theophylline]. 629 96

Effects of 2-ethoxyethanol (EE) on semen parameters in male rats were investigated employing an animal model that allowed assessment of toxicity and recovery in the same animal. Prior to exposure, 70-d-old Long-Evans hooded males were placed with ovariectomized, hormonally primed females on several occasions and their copulatory behaviors were monitored and scored. At 100 d of age, these males were mated with females that were sacrificed 15 min postejaculation. The semen sample was recovered from the female reproductive tract and scored for sperm motility, sperm count, and abnormal sperm morphology. Following this preexposure baseline assessment, the males were intubated with 0, 936, 1872, or 2808 mg EE/kg for 5 consecutive days. The males were mated weekly for the next 14 wk. Copulatory behaviors were monitored and ejaculated semen samples analyzed on wk 1, 4, 7, 10, and 14. The males were sacrificed at wk 16 and the testes and epididymides were processed for histological evaluation. Data analyses indicated that EE produced a rapid decline in sperm counts in the two highest groups, with most of the males becoming azoospermic by wk 7. The males in the low dose group also exhibited a significant decrease in sperm counts at this week. Additionally, there was a significant increase in abnormal sperm morphology at wk 7 in the low-dose males. Partial or complete recovery was apparent in the sperm parameters by wk 14, as evidenced by an increase in sperm counts and a decrease in abnormal morphology and further supported by epididymal and testicular histological assessment at wk 16. At sacrifice, there were no significant differences between groups on body weights, organ weights, or epididymal sperm counts, except for a significant depression of epididymal weight in the middle dose group. While high doses of EE produced a decline in sperm counts starting after the first week of exposure, the early spermatid-late spermatocyte stages, represented by mature spermatozoa in the wk 7 ejaculates, appeared to be particularly sensitive to this compound. Moreover, most of the males exhibited recovery following this acute dosing regimen.
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PMID:Male reproductive toxicity and recovery associated with acute ethoxyethanol exposure in rats. 649 98


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