Evaluation of 2-Year-Old Intrasplenic Fetal Liver Tissue Transplants in Rats

2003 ◽  
Vol 12 (4) ◽  
pp. 423-438 ◽  
Author(s):  
Amelie Lupp ◽  
Manfred Danz ◽  
Dieter Müller
Keyword(s):  
Liver Tissue ◽  
Fetal Liver ◽  
Male Rats ◽  
Surrounding Tissue ◽  
Transplant Recipients ◽  
Glutathione S Transferase ◽  
Tissue Transplants ◽  
Preneoplastic Foci ◽  
Isoform Expression ◽  
And Control

Liver cell transplantation into host organs like the spleen may possibly provide a temporary relief after extensive liver resection or severe liver disease or may enable treatment of an enzyme deficiency. With time, however, dedifferentiation or malignant transformation of the ectopically transplanted cells may be possible. Thus, in the present study syngenic fetal liver tissue suspensions were transplanted into the spleen of adult male rats and evaluated 2 years thereafter in comparison to orthotopic livers for histopathological changes and (as markers for preneoplastic transformation) for cytochrome P450 (P450) and glutathione S-transferase (GST) isoform expression. Because inducibility of P450 and GST isoforms may be changed in preneoplastic foci, prior to sacrifice animals were additionally treated either with β-naphthoflavone, phenobarbital, dexamethasone, or the respective solvent. In the 2-year-old grafts more than 70% of the spleen mass was occupied by the transplant. The transplanted hepatocytes were arranged in cord-like structures. Also few bile ducts were present. Morphologically, no signs of malignancy were visible. With all rats, transplant recipients as well as controls, however, discrete nodular structures were seen in the livers. Due to age, both livers and transplants displayed only a low P450 2B1 and 3A2 and GST class α and μ isoform expression. No immunostaining for P450 1A1 was visible. At both sites, β-naphthoflavone, phenobarbital, or dexamethasone treatment enhanced P450 1A1, P450 2B1 and 3A2, or P450 3A2 expression, respectively. No immunostaining for GST class π isoforms was seen in the transplants. The livers of both transplant recipients and control rats, however, displayed GST π-positive foci, corresponding to the nodular structures seen histomorphologically. Compared to the surrounding tissue, these foci also exhibited a more pronounced staining for GST class α and μ isoforms and a stronger inducibility of the P450 1A1 expression due to β-naphthoflavone. In conclusion, in contrast to the livers, no preneoplastic foci seem to appear in the intrasplenic transplants even 2 years after transplantation. This may be due either to the protection of these transplants by the orthotopic livers or to the different humoral and nerval influences at the ectopic site.

Influence of recipient gender on cytochrome P450 isoforms expression in intrasplenic fetal liver tissue transplants in rats

Toxicology ◽  
2003 ◽  
Vol 188 (2-3) ◽  
pp. 171-186 ◽  
Author(s):  
Amelie Lupp ◽  
Sabine Hugenschmidt ◽  
Manfred Danz ◽  
Dieter Müller
Keyword(s):  
Cytochrome P450 ◽  
Liver Tissue ◽  
Fetal Liver ◽  
Tissue Transplants ◽  
Cytochrome P450 Isoforms

scholarly journals Effects of Silybum marianum Aqueous Extract and L-carnitine on Stereological Changes in Diazinon-Treated Rat Liver

2020 ◽  
Vol 25 (2) ◽  
pp. 91
Author(s):  
Forough Masoumi ◽  
Mehrdad Shariati ◽  
Mokhtar Mokhtari
Keyword(s):  
Connective Tissue ◽  
Aqueous Extract ◽  
Liver Tissue ◽  
Liver Volume ◽  
Male Rats ◽  
Central Venous ◽  
Hepatocyte Nucleus ◽  
Tissue Volume ◽  
Venous Volume ◽  
And Control

As an organophosphorus, Diazinon (DZN) impairs liver tissue function by inhibiting acetylcholinesterase and causing oxidative stress. In this study, the effects of <em>Silybum</em><em> marianum </em>aqueous extract (SMAE) and L-carnitine (LC) on the stereological and histopathological changes of the liver in DZN-treated male rats were investigated. The rats in this study were placed into 9 groups of 8 each containing control, placebo, and a combination of DZN, SMAE, and LC. The animals received SMAE and chemicals orally for 30 days. At last, the liver tissue of all animals was removed. Then, tissue sections from the liver were provided to study the stereological markers including liver volume and weight, hepatocytes’ volume, central venous volume, sinusoidal volume, connective tissue volume, inflammation rate, and a number of the hepatocytes’ nuclei. Also, the sample tissues were evaluated histopathologically. Treatment with DZN significantly reduced the liver volume and weight, hepatocyte volume, central venous volume, sinusoidal volume, and hepatocyte nucleus number compared to placebo and control but it significantly increased the inflammation and volume of liver’s connective tissue. However, co-administration of SMAE and LC with DZN improved liver volume and weight, hepatocyte volume, central venous volume, sinusoidal volume, connective tissue volume, and hepatocyte nucleus number alone compared to the DZN treatment. Liver inflammation was also significantly decreased compared to the DZN treatment but comparing to the placebo and control groups, it increased significantly. Simultaneous administration of SMAE and LC has protective effects on liver tissue and can reduce DZN-induced liver injury in rats.

Influence of recipient gender on intrasplenic fetal liver tissue transplants in rats: cytochrome P450-mediated monooxygenase functions

Toxicology ◽  
2004 ◽  
Vol 197 (3) ◽  
pp. 199-212 ◽  
Author(s):  
Amelie Lupp ◽  
Sabine Hugenschmidt ◽  
Michael Rost ◽  
Dieter Müller
Keyword(s):  
Cytochrome P450 ◽  
Liver Tissue ◽  
Fetal Liver ◽  
Tissue Transplants

REPRODUCTIVE TOXICITY OF CHLORPYRIFOS, CYPERMETHRIN AND THEIR INTERACTION IN MALE ALBINO RATS

2018 ◽  
pp. 69-86
Author(s):  
Asmaa ELnamaky ◽  
Amal Halawa ◽  
Mamdouh Abouelmaged
Keyword(s):  
Reproductive Toxicity ◽  
Prostatic Acid Phosphatase ◽  
Serum Levels ◽  
Reproductive Organs ◽  
Male Rats ◽  
Albino Rats ◽  
Glutathione S Transferase ◽  
Significant Drop ◽  
Sperm Abnormalities ◽  
Pituitary Glands

he present work was designed to investigate the reproductive toxicity induced by oral administration of chlorpyrifos (CPF), cypermethrin (CYP) and their combination in adult male albino rats. Forty mature male albino rats were separated into four groups (10 each), the first group was used as control, while second, third and fourth groups received orally 1/20 LD50 of CPF (10 mg/kg b.wt), 1/20 LD50 of CYP (17.22 mg/kg b.wt) and 1/40 LD50 of CPF plus 1/40 LD50 of CYP (5 mg/kg b.wt CPF plus 8.61 mg/kg b.wt CYP) respectively for 26 days. The results revealed that exposure to CPF and/or CYP induced a significant decrease in the reproductive organs weight. Moreover, a significant decrease in spermatic picture (sperm cell concentration and viability) was observed with high percent of sperm abnormalities. Serum levels of testosterone and pituitary gonadotropins (FSH and LH) have been declined significantly in all treated groups. Significant elevations were observed in malondialdehyde and nitric oxide concentrations, while antioxidant enzymes superoxide dismutase and glutathione-S-transferase activities were decreased significantly as a result of induced oxidative stress. A significant drop in prostatic acid phosphatase activity was observed. Additionally, the results showed some histopathological alterations in the reproductive organs as well as neurological lesions in brain and pituitary glands. In conclusion, CPF and CYP induce deleterious effects on reproductive efficiency of male rats which reflect more obvious impacts when both combined

In Vivo Laser Tissue Welding in the Rabbit Maxillary Sinus

2008 ◽  
Vol 22 (6) ◽  
pp. 625-628 ◽  
Author(s):  
Benjamin S. Bleier ◽  
James N. Palmer ◽  
Michael A. Gratton ◽  
Noam A. Cohen
Keyword(s):  
Intracranial Pressure ◽  
Maxillary Sinus ◽  
Skull Base ◽  
Thermal Injury ◽  
Surrounding Tissue ◽  
Csf Leak ◽  
Tissue Welding ◽  
Laser Tissue Welding ◽  
And Control

Background One of the challenges in the current expansion of endoscopic sinonasal surgery is the ability to adequately reconstruct the skull base. Laser tissue welding (LTW) uses laser energy coupled to a biological solder to produce tissue bonds with burst thresholds exceeding human intracranial pressure. This technology could be used to reduce the rate of postoperative cerebrospinal fluid (CSF) leak. We performed this study to determine whether LTW can create durable tissue bonds in sinonasal mucosa that support normal wound healing and produce minimal collateral thermal injury. Methods Bilateral maxillary sinus mucosal incisions were made in 20 New Zealand white rabbits and one side was repaired using LTW. Burst pressure thresholds were measured on postoperative days 0, 5, and 15 and were compared with control using a two- way ANOVA and a post hoc Tukey test. Welds were examined histologically for thermal injury, inflammation, and fibroplasia and graded on a 4-point scale by three blinded observers. Results The burst pressures of the LTW group were significantly higher than control on postoperative day 0 (120.85 mm Hg, N = 4, SD = 47.84 versus 7.85 mm Hg, N = 4, SD = 0.78), and day 5 (132.56 mm Hg, N = 8, SD = 24.02 versus 41.7 mm Hg, N = 8, SD = 7.2; p < 0.05). By postoperative day 15 there was no significant difference between LTW (169.64 mm Hg, N = 8, SD = 18.49) and control (160.84 mm Hg, N = 8, SD = 14.16) burst thresholds. There was no evidence of thermal injury to the surrounding tissue in any group as well as no difference between experimental group and control with respect to inflammation or fibroplasia. Conclusion This is the first in vivo study showing that LTW is capable of producing tissue bonds exceeding human intracranial pressure with negligible thermal injury in sinonasal tissue. Welding can be performed endoscopically using a fiberoptic cable and may be useful in CSF leak and skull base repair.

scholarly journals Increased bioactivation of dihaloalkanes in rat liver due to induction of class Theta glutathione S-transferase T1-1

1998 ◽  
Vol 335 (3) ◽  
pp. 619-630 ◽  
Author(s):  
Philip J. SHERRATT ◽  
Margaret M. MANSON ◽  
Anne M. THOMSON ◽  
Erna A. M. HISSINK ◽  
Gordon E. NEAL ◽  
...  
Keyword(s):  
Western Blotting ◽  
Rat Liver ◽  
Female Rats ◽  
Male Rats ◽  
Male Rat ◽  
Female Rat ◽  
Glutathione S Transferase ◽  
Chemopreventive Agents ◽  
Cytoplasmic Staining ◽  
Potent Inducer

A characteristic feature of the class Theta glutathione S-transferase (GST) T1-1 is its ability to activate dichloromethane and dibromoethane by catalysing the formation of mutagenic conjugates. The level of the GSTT1 subunit within tissues is an important determinant of susceptibility to the carcinogenic effects of these dihaloalkanes. In the present study it is demonstrated that hepatic GST activity towards these compounds can be elevated significantly in female and male Fischer-344 rats by feeding these animals on diets supplemented with cancer chemopreventive agents. Immunoblotting experiments showed that increased activity towards the dihaloalkanes is associated with elevated levels of the GSTT1 subunit in rat liver. Sex-specific effects were observed in the induction of GSTT1 protein. Amongst the chemopreventive agents tested, indole-3-carbinol proved to be the most potent inducer of hepatic GSTT1 in male rats (6.2-fold), whereas coumarin was the most potent inducer of this subunit in the livers of female rats (3.5-fold). Phenobarbital showed significant induction of GSTT1 only in male rat liver and had little effect in female rat liver. Western blotting showed that class Alpha, Mu and Pi GST subunits are not co-ordinately induced with GSTT1, indicating that the expression of GSTT1 is determined, at least in part, by mechanisms distinct from those that regulate levels of other transferases. The increase in amount of hepatic GSTT1 protein was also reflected by an increase in the steady-state level of mRNA in response to treatment with chemopreventive agents and model inducers. Immunohistochemical detection of GSTT1 in rat liver supported the Western blotting data, but showed, in addition to cytoplasmic staining, significant nuclear localization of the enzyme in hepatocytes from some treated animals, including those fed on an oltipraz-containing diet. Significantly, the hepatic level of cytochrome P-450 2E1, an enzyme which offers a detoxification pathway for dihaloalkanes, was unchanged by the various inducing agents studied. It is concluded that the induction of GSTT1 by dietary components and its localization within cells are important factors that should be considered when assessing the risk dihaloalkanes pose to human health.

Dyspnoea and Thoracic Spinal Deformation in Rats after Oral Prizidilol (SK&F 92657-A2)

1986 ◽  
Vol 5 (3) ◽  
pp. 183-187 ◽  
Author(s):  
T. J. Sutton ◽  
A. J. Darby ◽  
P. Johnson ◽  
G. B. Leslie ◽  
T. F. Walker
Keyword(s):  
Cardiac Hypertrophy ◽  
Drug Effects ◽  
Male Rats ◽  
Thoracic Cavity ◽  
Control Groups ◽  
Thoracic Spinal ◽  
Spinal Lesion ◽  
Second Year ◽  
And Control ◽  
Body Damage

Prizidilol (SK&F 92657-A2), an anti-hypertensive agent, has undergone a range of prescribed toxicity studies required for the investigation of possible adverse drug effects. During the second year of the 2-year rat oral study, a variety of symptoms were exhibited by males receiving 1600 mg of the compound day–1kg–1 by gavage. These animals became lethargic, slouched and developed dyspnoea which became progressively more severe during the course of the study. Necropsy of the affected rats revealed severely haemorrhagic lungs, cardiac hypertrophy and lordosis of the spine into the thoracic cavity. At the 2-year terminal kill, a proportion of the male rats receiving 100 and 400 mg of prizidilol day–1kg–1 were identified with similar but less severe spinal deformation. No female was found with spinal changes but all the rats receiving prizidilol showed haemorrhagic lungs and enlarged hearts. The lordosis of the affected males was always confined to the thoracic spine and this, along with the cardiac hypertrophy, presumably led to marked reduction in the volume of the thoracic cavity, inducing the dyspnoea. Thoracic vertebral body damage, possibly a precursor to the spinal deformities, was found in male rats from both drug-treated and control groups. The nature of the spinal lesion is at present under investigation.

scholarly journals In vivo uptake of [14C]leucine by skeletal muscle ribosomes after injury in rats fed two levels of protein

1969 ◽  
Vol 23 (2) ◽  
pp. 271-280 ◽  
Author(s):  
V. R. Young ◽  
P. C. Huang
Keyword(s):  
Skeletal Muscle ◽  
Specific Activity ◽  
Male Rats ◽  
Thigh Muscle ◽  
Left Femur ◽  
The Right ◽  
And Control ◽  
The Relationship ◽  
In Vivo Uptake

1. After 14 days on a diet containing 5 or 25% casein male rats received a fracture of the left femur. Four hours before they were killed the injured and control rats were injected with [1-14C]leucine; the incorporation of radioactivity into an isolated fraction of skeletal muscle ribosomes was studied 6, 12, 24, 48, 72, 96 and 228 h after injury.2. The incorporation of [14C]leucine into the ribosome fraction in right thigh muscles dropped to 40% of control values 72 h after fracture in well-nourished rats and after 96 h with diets containing 5 or 25%, casein.3. The specific activity of the trichloroacetic acid-soluble fraction of muscle from injured rats was equal to or higher than that of the controls during the first 72 h but lower at 96 h.4. These results suggest that a reduced incorporation of amino acids by ribosomes from the right thigh muscle occurred on day 3 after fracture in the group receiving 25% casein but not in the group receiving 5% casein.5. Muscle RNA and DNA concentrations were not affected by the injury.6. The relationship between these findings and the loss of muscle N after injury is discussed.

scholarly journals The Influence of Age, Sex, Pregnancy, Starvation, and Other Factors on the Cytoplasmic Ribonucleoproteins of Rat Liver

1958 ◽  
Vol 4 (6) ◽  
pp. 771-776 ◽  
Author(s):  
Mary L. Petermann ◽  
Mary G. Hamilton
Keyword(s):  
Body Weight ◽  
Rat Liver ◽  
Liver Tissue ◽  
Microsomal Protein ◽  
Male Rats ◽  
Differential Centrifugation ◽  
Adult Males ◽  
Analytical Ultracentrifuge ◽  
Total Rna ◽  
Adult Females

Rat liver was homogenized in 0.88 M sucrose. The DNA and total RNA were determined, and the homogenate was fractionated by differential centrifugation. The pellets obtained between 30 minutes at 20,000 g and 180 minutes at 105,000 g were analyzed for RNA and nitrogen. The ribonucleoproteins were determined in the analytical ultracentrifuge. The non-pellet RNA was calculated by difference. The results are reported as amounts per 6.7 x 10-9 mg. of DNA. In young, growing male rats the amounts of microsomal protein and ribonucleoprotein B (83S) increased with age. Non-pregnant adult females showed less non-pellet RNA and much more ribonucleoprotein C (63S) than did adult males. During pregnancy both of these cell constituents reverted to levels characteristic for male animals. Starvation for 5 days resulted in a reduction in the mass of liver tissue, the non-pellet RNA, the microsomal protein, and ribonucleoproteins B and C. During recovery from starvation the return of the liver to normal paralleled the rate at which body weight was restored. Treatment with cortisone, 25 mg. per rat per day for 5 days, caused an increase in microsomal protein and a decrease in ribonucleoprotein B. Treatment with 6-mercapto-purine, 50 mg. per kilo per day for 5 days, caused little change in liver composition in either males or females.

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