Sex- and species-related differences in the biotransformation of isosorbide dinitrate by various tissues of the rabbit and rat

1987 ◽  
Vol 65 (7) ◽  
pp. 1478-1483 ◽  
Author(s):  
G. S. Tam ◽  
G. S. Marks ◽  
J. F. Brien ◽  
K. Nakatsu
Keyword(s):  
Skeletal Muscle ◽  
Sex Difference ◽  
Isosorbide Dinitrate ◽  
Species Difference ◽  
Rabbit Liver ◽  
Male Rat ◽  
Tissue Homogenate ◽  
Male Rabbit ◽  
Tissue Homogenates ◽  
Liver Homogenates

The biotransformation of isosorbide dinitrate (ISDN) by various tissues of the rabbit and rat was examined. Incubation of 2 × 10−7 M ISDN at 37 °C with tissue homogenates of liver, lung, kidney, intestine, skeletal muscle, aorta, and erythrocytes from the rabbit and rat resulted in a significant disappearance of ISDN after a 30-min incubation (also, 5-min incubation for liver). The disappearance of ISDN in each tissue homogenate was accompanied by an equimolar production of the mononitrate metabolites, isosorbide-2-mononitrate (2-ISMN) and isosorbide-5-mononitrate (5-ISMN), with the exception of liver homogenates where the loss of ISDN could not be accounted for by mononitrate formation. The relative rate of ISDN disappearance in various tissue homogenates was for the male rabbit, liver > lung ≈ intestine > kidney > erythrocytes ≈ skeletal muscle ≈ aorta; for the female rabbit, liver > kidney ≈ lung ≈ intestine > erythrocytes ≈ skeletal muscle ≈ aorta; and for the male rat, liver > intestine > erythrocytes > skeletal muscle > lung ≈ kidney. A sex difference in the percent disappearance of ISDN was observed in homogenates of lung and intestine from male and female rabbits. In addition, a sex difference in the ratio of metabolite (2-ISMN/5-ISMN) formed by denitration of ISDN was seen in homogenates of lung, skeletal muscle, and erythrocyte lysate. There was a species difference between the male rabbit and male rat, with respect to the loss of ISDN exhibited during incubation of ISDN with liver homogenates for 5 min; this was also observed for homogenates of lung, kidney, and intestine during a 30-min incubation. In addition, a similar species difference was observed for metabolite ratios obtained from these incubations. These results indicate that biotransformation of ISDN by liver and extrahepatic tissues may contribute to the high systemic clearance of this drug. The observed sex and species differences in the rate of ISDN disappearance and the metabolite ratio (2-ISMN/5-ISMN) in the various tissues may be due to hormonal and (or) genetic differences.

scholarly journals Studies on protein binding of antibiotics. IV. Effect of the binding of drug to 100,000*g supernatant fluid of rabbit liver homogenates on urinary excretion.

1982 ◽  
Vol 35 (11) ◽  
pp. 1603-1609
Author(s):  
YASUO WATANABE ◽  
RIEKO KITAYAMA ◽  
TOSHIO HAYASHI ◽  
YOSHIFUMI NAKASHIMA ◽  
MASASHI NOGUCHI ◽  
...  
Keyword(s):  
Protein Binding ◽  
Urinary Excretion ◽  
Rabbit Liver ◽  
Supernatant Fluid ◽  
Liver Homogenates

Nitric Oxide levels and the uNK cell aspects as clinical predictors in induction–inflammation model during pregnancy and neurological problem 

2020 ◽  
Vol 9 (2) ◽  
pp. 50-57
Author(s):  
Luiza Lucchesi de Oliveira ◽  
Eliana Mara Oliveira Lippe
Keyword(s):  
Nitric Oxide ◽  
Tissue Homogenate ◽  
Dependent Manner ◽  
Clinical Predictors ◽  
Paraffin Embedding ◽  
Unk Cells ◽  
Neurological Problem ◽  
Tissue Homogenates ◽  
Pregnant Mice ◽  
Neurological Injuries

The successful of pregnancy in humans and rodents occur between the interaction maternal and fetal interface, specially involving the participation of uNK cells. This interaction involved neo angiogenesis, placentation and presence of mediators like nitric oxide. During the pregnancy the administration of LPS in the dams can results in necrosis, preterm birth, IUGR, miscarriage or neurological problem. Once the uNK cells are activated, they can produce vasodilators, like NO. So, the main purpose of this study was to evaluate if LPS cause alteration in the uNK cells in pregnant mice and if the same behaviour can be detected by NO in the blood. Also we evaluated the effect of LPS to cause neurological injuries. To do that we used pregnant mice on gd 10th and those was treated with LPS for different times. Uterine samples were collected at 0.5,1,2 and 6hr after LPS treated and processed for paraffin embedding and tissue homogenate. The samples designated for paraffin embedding was performed the Dolichos biflorus (DBA) lectin cytochemistry and anti-iNOS immunocytochemistry. The samples designated to tissue homogenates were processed for SDS-PAGE and Western-blot using anti-iNOS and evaluate of NO concentration. We found after 2h LPS exposure the mice showed fever and low capacity to explore different environment. At the same time, we found increase in the nitrate/nitrito ratio in a dose dependent manner in the uterus after 2h LPS exposure. The uNK cells were the main cell that was staining for iNOS isoform. Also, we found that wall:lumen ratio is very higher in treated mice than the control mice. The LPS is able to induce the activation of uNK cells and this action is involved by releasing NO in higher amount. So, it is possible to consider the uNK cells as a potential element of maternal-fetal interface in the production of NO and knowing that the isoforms is reduced in these cells, a model of NOS inhibition could be considered to elucidate the participation of uNK cells as a possible cause of effectors loss or interruption of pregnancy.

scholarly journals Maternal conjugated linoleic acid supplementation reverses high-fat diet-induced skeletal muscle atrophy and inflammation in adult male rat offspring

2016 ◽  
Vol 310 (5) ◽  
pp. R432-R439 ◽  
Author(s):  
C. A. Pileggi ◽  
S. A. Segovia ◽  
J. F. Markworth ◽  
C. Gray ◽  
X. D. Zhang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Linoleic Acid ◽  
Conjugated Linoleic Acid ◽  
Muscle Development ◽  
Maternal Diet ◽  
Male Rat ◽  
Skeletal Muscle Development ◽  
High Fat ◽  
Rat Offspring ◽  
Total Fat

A high-saturated-fat diet (HFD) during pregnancy and lactation leads to metabolic disorders in offspring concomitant with increased adiposity and a proinflammatory phenotype in later life. During the fetal period, the impact of maternal diet on skeletal muscle development is poorly described, despite this tissue exerting a major influence on life-long metabolic health. This study investigated the effect of a maternal HFD on skeletal muscle anabolic, catabolic, and inflammatory signaling in adult rat offspring. Furthermore, the actions of maternal-supplemented conjugated linoleic acid (CLA) on these measures of muscle phenotype were investigated. A purified control diet (CD; 10% kcal fat), a CD supplemented with CLA (CLA; 10% kcal fat, 1% total fat as CLA), a high-fat (HFD; 45% kcal fat from lard), or a HFD supplemented with CLA (HFCLA; 45% kcal fat from lard, 1% total fat as CLA) was fed ad libitum to female Sprague-Dawley rats for 10 days before mating and throughout gestation and lactation. Male offspring received a standard chow diet from weaning, and the gastrocnemius was collected for analysis at day 150. Offspring from HF and HFCLA mothers displayed lower muscular protein content accompanied by elevated monocyte chemotactic protein-1, IL-6, and IL-1β concentrations. Phosphorylation of NF-κBp65 (Ser536) and expression of the catabolic E3 ligase muscle ring finger 1 (MuRF1) were increased in HF offspring, an effect reversed by maternal CLA supplementation. The present study demonstrates the importance of early life interventions to ameliorate the negative effects of poor maternal diet on offspring skeletal muscle development.

scholarly journals Intralesional Infiltrations of Cell-Free Filtrates Derived from Human Diabetic Tissues Delay the Healing Process and Recreate Diabetes Histopathological Changes in Healthy Rats

2021 ◽  
Vol 2 ◽  
Author(s):  
Jorge Berlanga-Acosta ◽  
Maday Fernández-Mayola ◽  
Yssel Mendoza-Marí ◽  
Ariana García-Ojalvo ◽  
Raymond J. Playford ◽  
...  
Keyword(s):  
Healing Process ◽  
Normal Subjects ◽  
Nerve Degeneration ◽  
Tissue Homogenate ◽  
Diabetic Rat ◽  
Metabolic Memory ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Medical Interventions ◽  
Tissue Homogenates

Lower limb ulcers in type-2 diabetic patients are a frequent complication that tributes to amputation and reduces survival. We hypothesized that diabetic healing impairment and other histopathologic hallmarks are mediated by a T2DM-induced tissue priming/metabolic memory that can be transferred from humans to healthy recipient animals and consequently reproduce diabetic donor’s phenotypes. We examined the effect of human T2DM tissue homogenates injected into non-diabetic rat excisional wounds. Fresh granulation tissue, popliteal artery, and peroneal nerve of patients with T2DM were obtained following amputation. Post-mammoplasty granulation and post-traumatic amputation-tissue of normal subjects acted as controls. The homogenates were intralesionally injected for 6–7 days into rats’ excisional thickness wounds. Infiltration with the different homogenates caused impaired wound closure, inflammation, nerve degeneration, and arterial thickening (all P < 0.01 vs relevant control) resembling histopathology of diabetic donor tissues. Control materials caused marginal inflammation only. Infiltration with glycated bovine albumin provoked inflammation and wound healing delay but did not induce arterial thickening. The reproduction of human diabetic traits in healthy recipient animals through a tissue homogenate support the notion on the existence of tissue metabolic memory-associated and transmissible factors, involved in the pathogenesis of diabetic complications. These may have futuristic clinical implications for medical interventions.

Purine metabolic pathways in rat hindlimb perfusion model during ischemia and reperfusion

1993 ◽  
Vol 265 (4) ◽  
pp. H1074-H1081 ◽  
Author(s):  
B. Soussi ◽  
K. Lagerwall ◽  
J. P. Idstrom ◽  
T. Schersten
Keyword(s):  
Skeletal Muscle ◽  
Blood Cell ◽  
Xanthine Oxidase ◽  
Flow Rate ◽  
Adenine Nucleotide ◽  
Vascular Endothelial Cell ◽  
Nucleotide Metabolism ◽  
Computer Simulation Model ◽  
Tissue Homogenates ◽  
Adenine Nucleotide Pool

The perfused rat hindlimb preparation was used with a blood cell-free perfusate to investigate alterations in the purine nucleotide metabolism, flow rate, perfusion pressure, and venous excretion in response to ischemia and ischemia followed by reperfusion in skeletal muscle. The development of a physical hindrance during postischemic reperfusion, indicated by an increase in reperfusion pressure and a decrease in flow rate, coincided with a 90% decrease in phosphocreatine and a 50-70% reduction in total adenine nucleotide pool. The reflow impairment could not be explained by blood cell plugging of the capillaries. Washout of several metabolites was demonstrated during reperfusion. Hypoxanthine accumulated intracellularly during ischemia, and a substantial amount of uric acid was excreted into the venous effluent during reperfusion. The experimental data were fitted into a computer simulation model of the purine pathways. The model indicated that AMP deaminase was the predominant enzymatic pathway for the AMP degradation. It was demonstrated that ATP preferably accumulated as inosine-5'-monophosphate during ischemia and that xanthine oxidase was undetectable in skeletal muscle tissue homogenates. However, vascular endothelial cell xanthine oxidase activity responsible for a free radical-induced reperfusion injury could not be excluded.

scholarly journals The change in thyroid hormone signaling by altered training intensity in male rat skeletal muscle

2016 ◽  
Vol 63 (8) ◽  
pp. 727-738 ◽  
Author(s):  
Ronny Lesmana ◽  
Toshiharu Iwasaki ◽  
Yuki Iizuka ◽  
Izuki Amano ◽  
Noriaki Shimokawa ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Thyroid Hormone ◽  
Male Rat ◽  
Hormone Signaling ◽  
Training Intensity ◽  
Rat Skeletal Muscle

THE PRESENCE OF A MITOSIS INHIBITOR IN THE SERUM AND LIVER OF ADULT RATS

1958 ◽  
Vol 36 (8) ◽  
pp. 855-859 ◽  
Author(s):  
H. F. Stich ◽  
M. L. Florian
Keyword(s):  
Partial Hepatectomy ◽  
Specific Inhibitor ◽  
Mitotic Rate ◽  
Regenerating Liver ◽  
Sprague Dawley ◽  
Adult Rats ◽  
Sprague Dawley Rats ◽  
Organ Specific ◽  
Tissue Homogenates ◽  
Liver Homogenates

The influence of serum and tissue homogenates on the mitotic rate of regenerating liver was tested. The following fractions were injected into Sprague–Dawley rats 24 hours after partial hepatectomy: (a) serum from normal 290–340 g. rats; (b) serum from rats 24 or 72 hours following partial hepatectomy; (c) liver homogenates from normal 290–340 g. rats; (d) regenerating liver homogenates (24 hours after partial hepatectomy); and, as controls, (e) brain homogenates representing non-mitotic tissues; (f) testes homogenates representing mitotically active tissues. Serum and liver from adult animals inhibit the onset of mitosis. Serum and regenerating liver from partially hepatectomized rats, as well as heterologous tissue, show no retarding effect.The results suggest the presence of an organ-specific inhibitor of mitosis in the serum and liver of adult animals.

A Comparison of the Relative Amounts of Tissue Esterases in Liver and Kidney Homogenates

1963 ◽  
Vol 46 (5) ◽  
pp. 863-868
Author(s):  
Sheila I Read ◽  
W P Mckinley
Keyword(s):  
Sex Difference ◽  
Gel Electrophoresis ◽  
Rabbit Kidney ◽  
Starch Gel Electrophoresis ◽  
Liver And Kidney ◽  
Starch Gel ◽  
Liver Homogenates

Abstract The relative amounts of the ali-esterases in beef and rabbit kidney and liver homogenates have been evaluated quantitatively, after resolution of the esterases by starch-gel electrophoresis. The relative amounts of total ali-esterases in livers and kidneys of a number of animals and fowl have been determined. The data presented and other unpublished data show that the ali-esterase content of tissues increases with age and that there is a sex difference.

scholarly journals Development of a New Assay for Complex I of the Respiratory Chain

2000 ◽  
Vol 46 (3) ◽  
pp. 345-350 ◽  
Author(s):  
Hilary Brooks ◽  
Stephan Krähenbühl
Keyword(s):  
Skeletal Muscle ◽  
Complex I ◽  
Human Skeletal Muscle ◽  
Specific Activity ◽  
Mitochondrial Diseases ◽  
Spectrophotometric Analysis ◽  
Isolated Mitochondria ◽  
Tissue Homogenates ◽  
Multiple Samples ◽  
Complex I Activity

Abstract Background: Measurement of complex I activity has been hampered by the large amounts of tissue required and the resulting turbidity of the assay solution, which makes spectrophotometric analysis difficult. We have developed a new assay for measuring the activity of complex I in isolated mitochondria that is also applicable to skeletal muscle homogenate in patients with suspected mitochondrial diseases. Methods: The method was a radioenzymatic assay based on the preferential oxidation of the 4B hydrogen of NADH by complex I. We prepared tritiated isoforms of NADH for both the respective 4A-3H and 4B-3H positions. Enzyme in the form of purified mitochondria or homogenate was prepared from rat or human skeletal muscle and incubated with the respective radioisotopes. The product (3H2O) was collected after charcoal adsorption of unreacted NADH and taken as an indicator of NADH oxidation. Sensitivity to rotenone was used as a measure of complex I specific activity. Results: The assay was linear with time and protein for isolated mitochondria and tissue homogenates from rats and humans. The Vmax and Km values obtained for 4B-NADH with isolated rat skeletal muscle mitochondria were 35 μmol/L and 90 μmol · min−1 · mg protein−1, respectively. The assay was reproducible and useable for routine measurements in human skeletal muscle. The sensitivity was >10-fold higher than the sensitivities of spectrophotometric techniques. Conclusions: The results of our studies demonstrate the successful development of a new assay for complex I that is rapid, easy to perform, and that enables the processing of multiple samples at one time.

Factors Affecting the Inactivation of Insulin-125I by Rat Adipose Tissue

1971 ◽  
Vol 49 (5) ◽  
pp. 457-463 ◽  
Author(s):  
Alfred Fessler ◽  
Bernard Rubinstein ◽  
David Rubinstein ◽  
John C. Beck
Keyword(s):  
Adipose Tissue ◽  
Free Fraction ◽  
Tissue Homogenate ◽  
Immunoreactive Insulin ◽  
Insulin Degradation ◽  
Factors Affecting ◽  
Free Iodine ◽  
Tissue Homogenates ◽  
Rat Adipose Tissue ◽  
Tissue Fraction

The degradation of insulin-125I by adipose tissue was determined by the appearance of 125I in the trichloroacetic acid (TCA) soluble tissue fraction. A maximum of 30% of the 125I appears as TCA-soluble material following incubation with adipose tissue homogenates. Destruction of immunoreactive insulin and insulin-like activities is, however, complete. The appearance of TCA-soluble 125I is due to proteolysis rather than to deiodination since it can be decreased by the addition of unlabelled insulin to the incubation mixture. No increase in free iodine could be detected. The degradation of insulin by intact adipose tissue is greater than by free adipocytes. Tissue homogenization greatly increases the rate of insulin degradation. Most of the insulin-degrading activity is found in the "fat-free" fraction of the tissue homogenate, but this activity is rapidly lost during incubation at 37 °C. In contrast the lesser activity in the fat layer remains stable at 37°. N-Ethylmaleimide, which inhibits breakdown of the hormone by homogenates, increases the degradation of insulin by adipocytes. These results indicate that caution must be employed in interpreting binding and destruction of iodinated insulin and raise the possibility that insulin may penetrate the cell prior to its destruction.

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