Characterization of Urothelial Inclusions in Male Wistar Han Rats Treated Orally With the Novel α2A-Adrenoceptor Agonist Tasipimidine

2021 ◽  
pp. 019262332110274
Author(s):  
Joost F. M. Lensen ◽  
Minja Hyttilä-Hopponen ◽  
Stefan Karlsson ◽  
Tarja Kuosmanen ◽  
Jyrki Lehtimäki ◽  
...  
Keyword(s):  
Oral Treatment ◽  
Muscle Layer ◽  
Urothelial Cells ◽  
Bladder Epithelium ◽  
Major Hemorrhage ◽  
Microvascular Leakage ◽  
Adrenoceptor Agonist ◽  
Male Wistar Rats ◽  
Eosinophilic Inclusions ◽  
High Doses

Intracellular inclusions were observed in urinary bladder epithelium of male Wistar rats, following oral treatment with high doses of the α2A-adrenoceptor agonist tasipimidine for 28 days. No cell death or inflammation was associated with the brightly eosinophilic inclusions. Electron microscopy (EM) studies showed that the inclusions represented intact or fragmented red blood cells (RBC) resulting from erythrophagocytosis, further supported by the presence of iron in urothelial cells. In addition, scattered iron-positive macrophages were observed in the submucosa and muscle layer, indicating microvascular leakage, as no major hemorrhage was evident. Despite the presence of inclusions, the urothelium showed normal uroplakin III distribution, normal cell turnover, and an absence of α-2u-globulin. It is, therefore, concluded that the inclusions were not associated with urothelial damage or increased renewal of the epithelium. This finding shows also that urothelial cells have the capability to phagocytize and break down RBCs originating from submucosal microvascular leakage. Similar changes were not observed in tasipimidine-treated beagle dogs (28 days), suggesting these findings were rat specific. The leakage of RBCs into the urothelium is suggested to be a consequence of exaggerated pharmacology leading to vasoconstriction of submucosal blood vessels in combination with transient increased bladder distension and pressure.

scholarly journals Thyroxine Induces Acute Relaxation of Rat Skeletal Muscle Arteries via Integrin αvβ3, ERK1/2 and Integrin-Linked Kinase

2021 ◽  
Vol 12 ◽  
Author(s):  
Ekaterina K. Selivanova ◽  
Dina K. Gaynullina ◽  
Olga S. Tarasova
Keyword(s):  
Skeletal Muscle ◽  
Kinase Inhibitors ◽  
Isometric Force ◽  
Rho Kinase ◽  
Integrin Αvβ3 ◽  
Acute Effects ◽  
Rat Skeletal Muscle ◽  
Subsequent Decrease ◽  
Adrenoceptor Agonist ◽  
Male Wistar Rats

Aim: Hyperthyroidism is associated with a decreased peripheral vascular resistance, which could be caused by the vasodilator genomic or non-genomic effects of thyroid hormones (TH). Non-genomic, or acute, effects develop within several minutes and involve a wide tissue-specific spectrum of molecular pathways poorly studied in vasculature. We aimed to investigate the mechanisms of acute effects of TH on rat skeletal muscle arteries.Methods: Sural arteries from male Wistar rats were used for isometric force recording (wire myography) and phosphorylated protein content measurement (Western blotting).Results: Both triiodothyronine (T3) and thyroxine (T4) reduced contractile response of sural arteries to α1-adrenoceptor agonist methoxamine. The effect of T4 was more prominent than T3 and not affected by iopanoic acid, an inhibitor of deiodinase 2. Endothelium denudation abolished the effect of T3, but not T4. Integrin αvβ3 inhibitor tetrac abolished the effect of T4 in endothelium-denuded arteries. T4 weakened methoxamine-induced elevation of phospho-MLC2 (Ser19) content in arterial samples. The effect of T4 in endothelium-denuded arteries was abolished by inhibiting ERK1/2 activation with U0126 as well as by ILK inhibitor Cpd22 but persisted in the presence of Src- or Rho-kinase inhibitors (PP2 and Y27632, respectively).Conclusion: Acute non-genomic relaxation of sural arteries induced by T3 is endothelium-dependent and that induced by T4 is endothelium-independent. The effect of T4 on α1-adrenergic contraction is stronger compared to T3 and involves the suppression of extracellular matrix signaling via integrin αvβ3, ERK1/2 and ILK with subsequent decrease of MLC2 (Ser19) phosphorylation.

scholarly journals Protection from Radiation-induced Damage in Rat’s Ileum and Colon by Combined Regimens of Melatonin and Metformin: A Histopathological Study

2020 ◽  
Vol 19 (2) ◽  
pp. 180-189 ◽  
Author(s):  
Masoud Najafi ◽  
Mohsen Cheki ◽  
Gholamreza Hassanzadeh ◽  
Peyman Amini ◽  
Dheyauldeen Shabeeb ◽  
...  
Keyword(s):  
Whole Body ◽  
Gastrointestinal Disorders ◽  
Histopathological Study ◽  
Radiation Toxicity ◽  
Pharmaceutical Treatment ◽  
Tissue Samples ◽  
Melatonin Administration ◽  
Male Wistar Rats ◽  
Radiation Induced ◽  
High Doses

Background: Radiation-induced enteritis and proctitis are common side effects of abdominopelvic cancers among patients that undergo radiotherapy for prostate, colorectal or urinary cancers. Exposure of these tissues to high doses of radiation leads to damage to villous, inflammation, pain, ulcer and bleeding, which may cause malabsorption and gastrointestinal disorders. To date, several procedures such as pharmaceutical treatment have been proposed for protection and mitigation of gastrointestinal toxicity following radiotherapy. Aims: In the current study, we aimed to investigate the possible radioprotection of ileum and colon in rats using a combination of melatonin and metformin. Methods: In this experimental study, 30 male Wistar rats were randomly assigned to six groups: control, melatonin (100 mg/kg) treatment, melatonin (100 mg/kg) plus metformin (100 mg/kg) treatment, radiation (10 Gy to whole body) group, radiation + melatonin (100 mg/kg) treatment, and radiation + melatonin (100 mg/kg) plus metformin (100 mg/kg) treatment. After 3.5 days, rats were sacrificed and their ileum and colon tissues carefully removed. Histopathological evaluations were conducted on these tissue samples. Results: Histological evaluations reported moderate to severe damages to ileum and colon following whole body irradiation. Melatonin administration was able to protect the ileum remarkably, while the combination of melatonin and metformin was less effective. Interestingly, for the colon, melatonin was less effective while its combination with metformin was able to protect against radiation toxicity completely. Conclusion: For the ileum, melatonin was a more effective radioprotector compared to its combination with metformin. However, the combination of melatonin and metformin can be proposed as an ideal radioprotector for the colon.

The effects of oral treatment with transfluthrin on the urothelium of rats and its metabolite, tetrafluorobenzoic acid on urothelial cells in vitro

2011 ◽  
Vol 49 (6) ◽  
pp. 1215-1223 ◽  
Author(s):  
Masanao Yokohira ◽  
Lora L. Arnold ◽  
Sophie Lautraite ◽  
Larry Sheets ◽  
Sheila Wason ◽  
...  
Keyword(s):  
Oral Treatment ◽  
Urothelial Cells ◽  
Tetrafluorobenzoic Acid

Anticonflict effect of high doses of testosterone in male wistar rats

1996 ◽  
Vol 6 ◽  
pp. 77-78
Author(s):  
O. Bing ◽  
M. Heilig ◽  
P. Kakaoulidis ◽  
C. Sundblad ◽  
E. Eriksson
Keyword(s):  
Wistar Rats ◽  
Male Wistar Rats ◽  
High Doses ◽  
Anticonflict Effect

scholarly journals The Green Bitter Weed (Hymenoxys odorato) Plant Extract Is Toxic to the Liver and Kidney of Wistar Rats

2018 ◽  
Author(s):  
John Juma Ochieng ◽  
Isaac Echoru ◽  
Musa Ajibola Iyiola
Keyword(s):  
Body Weight ◽  
Wistar Rats ◽  
Complete Blood Count ◽  
Medical Personnel ◽  
Control Group ◽  
Dependent Manner ◽  
Snake Bites ◽  
Male Wistar Rats ◽  
Liver And Kidney ◽  
High Doses

Background: Medicinal plants are of great importance to health of individual and communities. About 80% of the population in Uganda relies on traditional medicine because western-trained medical personnel are limited especially in villages. Most Ugandans use Hymenoxys odorato for medicinal purposes e.g. to treat colds, fever, coughs, anti-helminthes, locally used as tea, anti-allergy and also as an anti-venom to relieve snake bites. Method: A group of 25 male wistar rats of 150 g–210 g were kept for 14 days while being fed and treated with the extract. At 14th day, anesthesia was given and blood samples collected by cardiac puncture for hematological and biochemical investigations. Serum was analyzed for Alkaline Phosphatase, Aspartate Transaminase and Alanine Transaminase while whole blood was used for complete blood count. The liver and kidney were removed and placed in 10% formalin to prepare for histology staining using haematoxylin and eosin technique. Results: The extract elevated hepatic biomarker enzymes i.e. ALP, ALT and AST. The increase was found to be significantly different (P > 0.05) at 400 and 500 mg/kg doses as compared to the control group. Histological sections of the liver showed distortion of liver cytoarchitecture, steatosis, necrosis of hepatocytes and congestion of the sinusoids at high doses 300, 400 and 500 mg/kg body weight. In the sections of the kidney, there was mild distortion of the integrity of the kidney with glomerular hypercellularity at high doses (400 and 500 mg/kg per body weight). Conclusion: Hymenoxys odorato aqueous extract has toxic effects on the liver and kidney of wistar rats. The effects were observed to be in a dose dependent manner.

Phoenix dactylifera, Cyperus esculentus, and Cocos nucifera Pooled Extracts Ameliorate Pesticides-induced Hormonal Toxicity and Maintains Testicular Histology in Rats

2020 ◽  
Vol 15 (2) ◽  
pp. 43-51
Author(s):  
B.E. Ogeyemhe ◽  
P.U. Achukwu ◽  
E.B. Odigie
Keyword(s):  
Oral Treatment ◽  
Cocos Nucifera ◽  
Phoenix Dactylifera ◽  
Equal Proportion ◽  
Cyperus Esculentus ◽  
Testicular Weight ◽  
Before And After ◽  
Male Wistar Rats ◽  
Group B ◽  
Testicular Histology

Male infertility is increasingly worrisome and has been linked to increase rate of hormonal toxicity and imbalance. Sufferers now result to using medicinal plants due to its availability and cost effectiveness. This study was to assess ameliorating effects of Phoenix dactylifera (date), Cyperus esculentus (tigernut) and Cocos nucifera (coconut)mixture on pesticides-induced hormonal toxicity in male Wistar rats. Aqueous extraction of crops - date (maceration apparatus), tiger nut (rotary evaporator) and coconut (spray drying process) wereconducted after which, 5g of each extract were mixed in equal proportion. Hormonal toxicity was induced in rats using Ochratoxin A and endosulfan before oral treatment of the mix at graded doses (250 to 1000 mg/kg/day) for 28 days. Aseptic bloodsample was obtained before and after treatment for hormonal assay. At termination, animals were euthanized via decapitation; organs were excised, processed histologically, stained with H&E, and testes examined microscopically. Hormonal toxicity in rats was successfully induced, body weight of highly treated rats reduced (P ≤ 0.02) while testicular weight increased insignificantly (P ≥ 0.05). Mixed extract ameliorated the effect of pesticides on testosterone levels in group: B (1.8 ± 0.5ng/dL), C (2.4 ± 0.4ng/dL), D (3.8 ± 0.6 ng/dL) and E (4.1 ± 0.3 ng/dL) including FSH and LH values (P ≤ 0.05). Stained sections of testis were in keeping with normal histology after investigations. High doses of extract mix successfully reversed pesticides-induced hormonal toxicity in rats without harming the testes. Keywords: Cocos nucifera, Coconut, Cyperus esculentus, Date, Hormonal imbalance, Pesticide, Phoenix dactylifera, and Tiger nut

scholarly journals Bidirectional regulation of renal cortical Na+,K+-ATPase by protein kinase C.

2004 ◽  
Vol 51 (3) ◽  
pp. 757-772 ◽  
Author(s):  
Jerzy Bełtowski ◽  
Andrzej Marciniak ◽  
Anna Jamroz-Wiśniewska ◽  
Ewelina Borkowska ◽  
Grazyna Wójcicka
Keyword(s):  
Cytochrome P450 ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Atpase Activity ◽  
Inhibitory Effect ◽  
Kinase C ◽  
Bidirectional Regulation ◽  
Male Wistar Rats ◽  
Arachidonate Metabolites ◽  
High Doses

We examined the role of protein kinase C (PKC) in the regulation of Na+,K+- ATPase activity in the renal cortex. Male Wistar rats were anaesthetized and the investigated reagents were infused into the abdominal aorta proximally to the renal arteries. A PKC-activating phorbol ester, phorbol 12,13-dibutyrate (PDBu), had a dose-dependent effect on cortical Na+,K+-ATPase activity. Low dose of PDBu (10(-11) mol/kg per min) increased cortical Na+,K+-ATPase activity by 34.2%, whereas high doses (10(-9) and 10(-8) mol/kg per min) reduced this activity by 22.7% and 35.0%, respectively. PDBu administration caused changes in Na+,K+-ATPase Vmax without affecting K(0.5) for Na+, K+ and ATP as well as Ki for ouabain. The effects of PDBu were abolished by PKC inhibitors, staurosporine, GF109203X, and Gö 6976. The inhibitory effect of PDBu was reversed by pretreatment with inhibitors of cytochrome P450-dependent arachidonate metabolism, ethoxyresorufin and 17-octadecynoic acid, inhibitors of phosphatidylinositol 3-kinase (PI3K), wortmannin and LY294002, and by actin depolymerizing agents, cytochalasin D and latrunculin B. These results suggest that PKC may either stimulate or inhibit renal cortical Na+,K+-ATPase. The inhibitory effect is mediated by cytochrome P450-dependent arachidonate metabolites and PI3K, and is caused by redistribution of the sodium pump from the plasma membrane to the inactive intracellular pool.

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