Effect of bacterial endotoxemia on succinic dehydrogenase of liver and kidney of rabbit

1961 ◽  
Vol 201 (1) ◽  
pp. 16-18 ◽  
Author(s):  
J. Cascarano ◽  
A. D. Rubin ◽  
A. K. Neumann ◽  
B. W. Zweifach
Keyword(s):  
Succinic Dehydrogenase ◽  
Significant Inhibition ◽  
Frozen Sections ◽  
Experimental Animals ◽  
E Coli ◽  
Fresh Frozen ◽  
Tissue Homogenates ◽  
Liver And Kidney ◽  
Lethal Doses

The in vivo inhibition of liver and kidney succinic dehydrogenase by administration of lethal doses of bacterial endotoxin ( Escherichia coli and Salmonella typhosa) was investigated. Quantitative determinations conducted on tissue homogenates revealed significant inhibition of activity only in liver of rabbits injected with E. coli lipopolysaccharide. The histochemical distribution of succinic dehydrogenase in fresh frozen sections of kidney was the same in both control and experimental animals. However, the centrolobular areas of liver appeared considerably depressed in activity in both E. coli and S. typhosa endotoxin-treated animals. These data, along with those presented by other studies in the literature, suggest that the action of endotoxin appears to be restricted to certain cells.

scholarly journals Inhibition of intravascular fibrin deposition by dipyridamole in experimental animals

Blood ◽  
1975 ◽  
Vol 45 (4) ◽  
pp. 569-575
Author(s):  
V Gurewich ◽  
B Lipinski ◽  
R Wetmore
Keyword(s):  
Reticuloendothelial System ◽  
Experimental Models ◽  
Significant Inhibition ◽  
Fibrin Deposition ◽  
Experimental Animals ◽  
Fibrin Monomer

Intravascular fibrin deposition was induced in rabbits by endotoxin, the infusion of fibrin monomer (FM), and by the infusion of thrombin and EACA. A previously developed radioisotope technique was used to measure the fibrin deposits in various organs. Dipyridamole treatment of rabbits caused significant inhibition of fibrin deposition in all three experimental models. The drug also inhibited platelet consumption and, in the thrombin- and EACA-infused animals, fibrinogen consumption as well. The results obtained with dipyridamole were compared with the effect of thorotrast. It was concluded from this comparison that the effect of dipyridamole could not be attributed to inhibition of the reticuloendothelial system. It is postulated that dipyridamole inhibits the final step at which soluble FM is precipitated as fibrin in vivo.

scholarly journals The effects of a dietary excess of leucine on the synthesis of nicotinamide nucleotides in the rat

1983 ◽  
Vol 49 (3) ◽  
pp. 321-329 ◽  
Author(s):  
Bahieldin I. Magboul ◽  
David A. Bender
Keyword(s):  
Significant Inhibition ◽  
Nucleotide Synthesis ◽  
Tryptophan Oxygenase ◽  
Rate Limiting Step ◽  
Minimum Requirements ◽  
Tissue Homogenates ◽  
Rate Limiting ◽  
Competitive Nature ◽  
Precipitating Factor

1. In order to test the suggestion that a dietary excess of leucine may be a precipitating factor in pellagra, rats were fed on diets that provided 15 g leucine/kg in excess of requirements for 7 weeks from weaning. This led to a significant reduction in the concentrations of nicotinamide nucleotides in liver and blood. The effect was only apparent when the diets provided less than a minimally adequate amount of nicotinamide, so that the animals were dependent on the synthesis of nicotinamide nucleotides from tryptophan to meet all or part of their requirements.2. Urinary excretion of N1-methyl nicotinamide was not a useful indicator of tissue concentrations of nicotinamide nucleotides, and seemed not to be adequately sensitive to differentiate between minimal adequacy and marginal deficiency, as demonstrated by changes in concentrations of nicotinamide nucleotides in liver and blood.3. The addition of leucine to incubation media for the measurement of enzyme activity in tissue homogenates at concentrations within the physiological range, led to a significant activation of tryptophan oxygenase (L-tryptophan: oxygen oxidoreductase (decyclizing), EC 1.13.11.11) and significant inhibition of kynureninase (L-kynurenine hydrolase, EC 3.7.1.3). The effect on tryptophan oxygenase may not be physiologically significant, in view of the considerable range of activity of this enzyme under normal conditions. However, the inhibition of kynureninase, which was primarily competitive with respect to the substrate, probably is physiologically significant, and was enough for this enzyme to become a probable rate-limiting step in tryptophan metabolism and nicotinamide nucleotide synthesis. Other enzymes of the tryptophan – nicotinamide nucleotide pathway were not affected by the addition of leucine to the incubation medium.4. Feeding 15 g leucine/kg diet in excess of minimum requirements had no effect on the activities of tryptophan oxygenase or kynureninase in liver homogenates. This may reflect the reversible competitive nature of the inhibition of kynureninase by leucine, and hence be an artefact of the incubation procedure. Rats fed on the high-leucine diets excreted significantly more kynurenine than did control animals, which is evidence of inhibition of kynureninase in vivo.5. It appears that a dietary excess of leucine, of the order of 15 g/kg above requirements, may be a precipitating factor in pellagra when there is reliance on the synthesis of nicotinamide nucleotides from tryptophan to meet a part or all of the requirements, but not when minimally adequate niacin is available from the diet.

scholarly journals In vivotransfer of R factors betweenEscherichia colistrains inoculated into the rumen of sheep

1975 ◽  
Vol 75 (3) ◽  
pp. 363-370 ◽  
Author(s):  
M. G. Smith
Keyword(s):  
Population Density ◽  
Antibiotic Treatment ◽  
Intestinal Tract ◽  
Total Coliform ◽  
Starvation Period ◽  
Experimental Animals ◽  
E Coli ◽  
R Factor ◽  
R Factors

SUMMARYSubstantial transfer of R factors occurredin vivo, under certain conditions, in the rumen of adult sheep in the absence of any antibiotic treatment. A starvation period of 24–48 hr. was required to produce the conditions necessary, when even quite low inocula (ca. 103cells) of donor and recipientE. colicould grow within the rumen and reach a population density sufficient for transfer to take place. The results indicate that under the same conditions R factors may be transferred between organisms in the lower intestinal tract also. Without the starvation period, the inoculation of even massive numbers (1010cells) of the same organisms resulted in almost no detectable transfer.Some of the experimental animals on which a starvation period was imposed became carriers of either the inoculated recipientE. coli, or of R factor bearing coliforms, and these formed 1–10% of the total coliform population of the faeces for at least 6 weeks.

scholarly journals FORMALIN FIXATION IN THE CYTOCHEMICAL DEMONSTRATION OF SUCCINIC DEHYDROGENASE OF MITOCHONDRIA

1961 ◽  
Vol 9 (2) ◽  
pp. 415-427 ◽  
Author(s):  
Donald G. Walker ◽  
Arnold M. Seligman
Keyword(s):  
Divalent Cations ◽  
Succinic Dehydrogenase ◽  
Staining Procedure ◽  
Frozen Sections ◽  
Tissue Slices ◽  
Fixed Tissue ◽  
Cytochemical Demonstration ◽  
Hematoxylin Staining ◽  
Fresh Frozen ◽  
Duodenal Epithelium

A variety of established methods for protecting mitochondria were tested on rat duodenal epithelium during the histochemical assay for succinic dehydrogenase. The use of sucrose at isotonic or hypertonic concentrations, 7.5 per cent polyvinylpyrrolidone, divalent cations, physiological salt solutions, phenazine methosulfate, coenzyme Q10, and menadione failed to improve the quality of the histochemical preparation once fresh frozen sections were prepared. However, preservation of mitochondrial integrity with little diminution in succinic dehydrogenase activity was obtained by fixing tissue slices (less than 1 mm. in thickness) in 8 per cent unneutralized, aqueous formaldehyde from 8 to 16 minutes at from 5° to 10°C. prior to freezing. To offset the inhibition of enzymatic activity it was necessary to extend the incubation period by 10 to 15 minutes. Two-micron-thick sections were easily obtained from the frozen blocks of such fixed tissue and incubated in the unmodified Nitro—BT-succinate medium. Once the optimum conditions for fixation of intestinal epithelium were determined, many other tissues were subjected to the same procedure. From the morphological standpoint the appearance of the mitochondria in these histochemical preparations compares favorably with the results obtained using the classical Regaud iron-hematoxylin staining procedure. With most tissues, the results are superior to those with fresh frozen sections. However, results with muscle, sperm, and kidney tubular epithelium are not as strikingly improved as with gut and liver.

Embolic fat as a measure of adequacy of various oxygenators

1960 ◽  
Vol 15 (6) ◽  
pp. 999-1000 ◽  
Author(s):  
Guy Owens ◽  
Jesse E. Adams ◽  
H. W. Scott
Keyword(s):  
Cardiopulmonary Bypass ◽  
Direct Contact ◽  
Kidney Tissue ◽  
Frozen Sections ◽  
Membrane Oxygenator ◽  
Vascular Tree ◽  
Experimental Animals ◽  
Liver And Kidney ◽  
Sudan Iv ◽  
Membrane Oxygenators

Previous work has demonstrated that prolonged employment of the filming oxygenator in bypass procedures is associated with considerable deposition of embolic fat within the vascular tree of both humans and experimental animals. Mongrel dogs were subjected to 2 hours of cardiopulmonary bypass in which macrobubble and membrane oxygenators were employed. All other conditions were standardized. All animals were sacrificed shortly after restoration of normal clotting and cardiac function. Brain, lung, liver and kidney specimens were fixed for 24 hours in 10% formalin, after which frozen sections were made and stained with Sudan IV and hematoxylin. Embolic fat was found extensively in brain, liver and kidney tissue in the five animals in which the macrobubble device had been employed. The quantity of fat appeared similar to that previously noted in animals in which the filming device had been used. No fat emboli were noted in tissues obtained from the four animals exposed to the membrane oxygenator. This suggests that the direct contact of blood and gas contributes to the development of embolic fat. Submitted on June 15, 1960

scholarly journals Effective Control of Salmonella Infections by Employing Combinations of Recombinant Antimicrobial Human β-Defensins hBD-1 and hBD-2

2014 ◽  
Vol 58 (11) ◽  
pp. 6896-6903 ◽  
Author(s):  
Soumitra Maiti ◽  
Sunita Patro ◽  
Sukumar Purohit ◽  
Sumeet Jain ◽  
Shantibhusan Senapati ◽  
...  
Keyword(s):  
Bacterial Population ◽  
Antibacterial Activities ◽  
Effective Control ◽  
Content Type ◽  
E Coli ◽  
Salmonella Infections ◽  
Functional Peptides ◽  
Lethal Doses

ABSTRACTWe successfully produced two human β-defensins (hBD-1 and hBD-2) in bacteria as functional peptides and tested their antibacterial activities againstSalmonella entericaserovar Typhi,Escherichia coli, andStaphylococcus aureusemploying both spectroscopic and viable CFU count methods. Purified peptides showed approximately 50% inhibition of the bacterial population when used individually and up to 90% when used in combination. The 50% lethal doses (LD50) of hBD-1 againstS.Typhi,E. coli, andS. aureuswere 0.36, 0.40, and 0.69 μg/μl, respectively, while those for hBD-2 against the same bacteria were 0.38, 0.36, and 0.66 μg/μl, respectively. Moreover, we observed that bacterium-derived antimicrobial peptides were also effective in increasing survival time and decreasing bacterial loads in the peritoneal fluid, liver, and spleen of a mouse intraperitoneally infected withS.Typhi. The 1:1 hBD-1/hBD-2 combination showed maximum effectiveness in challenging theSalmonellainfectionin vitroandin vivo. We also observed less tissue damage and sepsis formation in the livers of infected mice after treatment with hBD-1 and hBD-2 peptides individually or in combination. Based on these findings, we conclude that bacterium-derived recombinant β-defensins (hBD-1 and hBD-2) are promising antimicrobial peptide (AMP)-based substances for the development of new therapeutics against typhoid fever.

Protein phosphatase inhibition and in vivo hepatotoxicity of microcystins

1993 ◽  
Vol 265 (2) ◽  
pp. G224-G230 ◽  
Author(s):  
M. T. Runnegar ◽  
S. Kong ◽  
N. Berndt
Keyword(s):  
Protein Phosphatase ◽  
Intraperitoneal Injection ◽  
Significant Inhibition ◽  
Protein Phosphatase 1 ◽  
Liver Protein ◽  
Protein Phosphatase Inhibition ◽  
Clinical Changes ◽  
Dose Dependent ◽  
Lethal Doses

Administration of microcystin (MCYST)-YM or -LR (peptide hepatotoxins produced by the cyanobacterium Microcystis aeruginosa) to mice resulted in the inhibition of liver protein phosphatase 1 and 2A activity. In all cases significant inhibition preceded or accompanied clinical changes due to MCYST intoxication. Fifteen minutes after intraperitoneal injection of lethal doses of MCYST-YM protein phosphatase activity was already decreased to 44% of controls, and by 60 min was further decreased to 22% of controls. The inhibition was dose dependent: intraperitoneal injection with 84 nmol/kg of MCYST-YM and 48 nmol/kg of MCYST-LR were the minimum doses required for significant inhibition at 60 min. Pretreatment of mice with 200 mumol/kg of rifamycin prevented the inhibition of liver protein phosphatase. The inhibition was tissue specific, with none detected in the kidneys, an organ that, unlike the liver, does not accumulate MCYST. In contrast to MCYST intoxication, lethal doses of phalloidin, a peptide hepatotoxin that produces clinical and pathological changes similar to MCYST, did not cause any inhibition of protein phosphatases.

scholarly journals Evaluation of Antiepileptic Effect of Cleome viscosa Linn. Leaves Extract in Experimental Animals

2021 ◽  
pp. 35-43
Author(s):  
Manish Kumar Shakya ◽  
Arif Naseer ◽  
Ranjit Singh
Keyword(s):  
Research Work ◽  
Significant Inhibition ◽  
Screening Methods ◽  
Maximal Electroshock ◽  
Significant Delay ◽  
Experimental Animals ◽  
Soxhlet Apparatus ◽  
Cleome Viscosa

Aim: The purpose of this study was to assess the antiepileptic effect of Cleome viscosa Linn. leaves extract in experimental animals. Study Design: The extraction process, acute toxicity study was determined using OECD guidelines, Priliminary phytochemical screening, Antiepileptic pharmacological screening methods and statistical analysis. Place and Duration of Study: The research work was conducted during 10 Jan. 2020 to 10 July 2020 at Dept. of Pharmacology, Rajiv academy for Pharmacy, Mathura (U.P), 281001, India. Methodology: The fresh leaves were shade dried and reduced in size to powder and extracted by soxhlet apparatus. The MECV, CECV and AECV were prepared and subjected to comparative phytochemical profiling for in-vitro analysis. Further the in-vivo screening models like maximal electroshock induced seizures (MES), picrotoxin (PTX) and pentylenetetrazole (PTZ) induced models are used to assess the anti-epileptic effects of the methanol, chloroform and aqueous extracts of Cleome viscosa. Results: The extracts were subjected to phytochemical tests and the carbohydrate, tannins, alkaloids, saponins, flavonoids, steroids and glycosides were found to be present. In the MES induced seizures, MECV (200 mg/kg) showed high significant inhibition on tonic hind limb extension (THLE) (9.33±0.33***), decrease in duration of stupor period (145.2 ± 2.59***) and decreased mortality significantly. In PTX induced model, MECV (200 mg/kg) showed high significant delay on the onset of convulsions (18.00±0.63***), decreased duration of convulsion (3.50 ± 0.18***) and decreased mortality significantly. In PTZ induced model, MECV and AECV (200mg/kg) showed high significant delay on the onset of convulsions (2.55 ± 0.10***), (2.50 ± 0.18***), decreased duration of convulsion (3.67 ± 0.11***), (4.33 ± 0.17**) and decreased mortality significantly. Conclusion: It is clear from the preceding that Cleome viscosa has antiepileptic properties.

scholarly journals A Pharmacokinetic and Pharmacodynamic Evaluation of the Anti-Hepatocellular Carcinoma Compound 4-N-Carbobenzoxy-gemcitabine (Cbz-dFdC)

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2218
Author(s):  
Yilin Sun ◽  
Jiankun Wang ◽  
Kun Hao
Keyword(s):  
Human Liver ◽  
Antitumor Effect ◽  
Intragastric Administration ◽  
Enzyme Kinetic ◽  
Tumor Bearing ◽  
Tissue Homogenates ◽  
Liver And Kidney ◽  
Carboxylesterase 1

Gemcitabine (dFdC) demonstrates significant effectiveness against solid tumors in vitro and in vivo; however, its clinical application is limited because it tends to easily undergo deamination metabolism. Therefore, we synthesized 4-N-carbobenzoxy-gemcitabine (Cbz-dFdC) as a lead prodrug and conducted a detailed pharmacokinetic, metabolic, and pharmacodynamic evaluation. After intragastric Cbz-dFdC administration, the Cmax of Cbz-dFdC and dFdC was 451.1 ± 106.7 and 1656.3 ± 431.5 ng/mL, respectively. The Tmax of Cbz-dFdC and dFdC was 2 and 4 h, respectively. After intragastric administration of Cbz-dFdC, this compound was mainly distributed in the intestine due to low carboxylesterase-1 (CES1) activity. Cbz-dFdC is activated by CES1 in both humans and rats. The enzyme kinetic curves were well fitted by the Michaelis–Menten equation in rats’ blood, plasma, and tissue homogenates and S9 of the liver and kidney, as well as human liver S9 and CES1 recombinase. The pharmacodynamic results showed that the Cbz-dFdC have a good antitumor effect in the HepG2 cell and in tumor-bearing mice, respectively. In general, Cbz-dFdC has good pharmaceutical characteristics and is therefore a good candidate for a potential prodrug.

scholarly journals Inhibition of intravascular fibrin deposition by dipyridamole in experimental animals

Blood ◽  
1975 ◽  
Vol 45 (4) ◽  
pp. 569-575 ◽  
Author(s):  
V Gurewich ◽  
B Lipinski ◽  
R Wetmore
Keyword(s):  
Reticuloendothelial System ◽  
Experimental Models ◽  
Significant Inhibition ◽  
Fibrin Deposition ◽  
Experimental Animals ◽  
Fibrin Monomer

Abstract Intravascular fibrin deposition was induced in rabbits by endotoxin, the infusion of fibrin monomer (FM), and by the infusion of thrombin and EACA. A previously developed radioisotope technique was used to measure the fibrin deposits in various organs. Dipyridamole treatment of rabbits caused significant inhibition of fibrin deposition in all three experimental models. The drug also inhibited platelet consumption and, in the thrombin- and EACA-infused animals, fibrinogen consumption as well. The results obtained with dipyridamole were compared with the effect of thorotrast. It was concluded from this comparison that the effect of dipyridamole could not be attributed to inhibition of the reticuloendothelial system. It is postulated that dipyridamole inhibits the final step at which soluble FM is precipitated as fibrin in vivo.

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