EFFECT OF CORTISONE ON THE INTRACELLULAR DISTRIBUTION OF PHOSPHATASES AND RIBONUCLEASES IN RAT LIVER

1956 ◽  
Vol 34 (2) ◽  
pp. 170-179 ◽  
Author(s):  
Claude Allard ◽  
Gaston De Lamirande ◽  
George Weber ◽  
Antonio Cantero

The effect of cortisone acetate administration on the mitochondrial population and intracellular distribution of phosphatases and ribonucleases was investigated. Cortisone acetate was administrated at a dosage of 25 mgm. per 100 gm. body weight, daily, during five days and sacrificed on the sixth day. The livers of these animals were removed and homogenized in 0.25 M sucrose and subjected to differential centrifugation to prepare nuclear, mitochondrial, microsomal, and supernatant fractions. Nuclear and mitochondrial counts were made for each homogenate prepared. From these the number of mitochondria per average cell was computed. The intracellular distribution of RNAase and PO4ase activities was determined and expressed per average cell and per liver/body weight ratio. The activity of the mitochondrial fraction was also expressed per average mitochondrion. Results of this investigation showed that cortisone lowered the number of large granules per liver cell without influencing the acid PO4ase and acid and alkaline RNAase activities per cell. This suggested that mitochondria isolated from cortisone treated rats possessed abnormally high acid PO4ase and RNAase activities or/and that the remaining population of granules was different from the one in liver cells of untreated animals. The investigation of alkaline phosphatase revealed that cortisone increased the Mg++ sensitive alkaline PO4ase localized in the supernatant fluid without influencing the Mg++ insensitive enzyme.

1956 ◽  
Vol 34 (1) ◽  
pp. 170-179 ◽  
Author(s):  
Claude Allard ◽  
Gaston De Lamirande ◽  
George Weber ◽  
Antonio Cantero

The effect of cortisone acetate administration on the mitochondrial population and intracellular distribution of phosphatases and ribonucleases was investigated. Cortisone acetate was administrated at a dosage of 25 mgm. per 100 gm. body weight, daily, during five days and sacrificed on the sixth day. The livers of these animals were removed and homogenized in 0.25 M sucrose and subjected to differential centrifugation to prepare nuclear, mitochondrial, microsomal, and supernatant fractions. Nuclear and mitochondrial counts were made for each homogenate prepared. From these the number of mitochondria per average cell was computed. The intracellular distribution of RNAase and PO4ase activities was determined and expressed per average cell and per liver/body weight ratio. The activity of the mitochondrial fraction was also expressed per average mitochondrion. Results of this investigation showed that cortisone lowered the number of large granules per liver cell without influencing the acid PO4ase and acid and alkaline RNAase activities per cell. This suggested that mitochondria isolated from cortisone treated rats possessed abnormally high acid PO4ase and RNAase activities or/and that the remaining population of granules was different from the one in liver cells of untreated animals. The investigation of alkaline phosphatase revealed that cortisone increased the Mg++ sensitive alkaline PO4ase localized in the supernatant fluid without influencing the Mg++ insensitive enzyme.


Nutrients ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 41
Author(s):  
Nouf Aljobaily ◽  
Michael J. Viereckl ◽  
David S. Hydock ◽  
Hend Aljobaily ◽  
Tsung-Yen Wu ◽  
...  

Background: Treatment with the chemotherapy drug doxorubicin (DOX) may lead to toxicities that affect non-cancer cells including the liver. Supplementing the diet with creatine (Cr) has been suggested as a potential intervention to minimize DOX-induced side effects, but its effect in alleviating DOX-induced hepatoxicity is currently unknown. Therefore, we aimed to examine the effects of Cr supplementation on DOX-induced liver damage. Methods: Male Sprague-Dawley rats were fed a diet supplemented with 2% Cr for four weeks, 4% Cr for one week followed by 2% Cr for three more weeks, or control diet for four weeks. Animals then received either a bolus i.p. injection of DOX (15 mg/kg) or saline as a placebo. Animals were then sacrificed five days-post injection and markers of hepatoxicity were analyzed using the liver-to-body weight ratio, aspartate transaminase (AST)-to- alanine aminotransferase (ALT) ratio, alkaline phosphatase (ALP), lipemia, and T-Bilirubin. In addition, hematoxylin and eosin (H&E) staining, Picro-Sirius Red staining, and immunofluorescence staining for CD45, 8-OHdG, and β-galactosidase were performed to evaluate liver morphology, fibrosis, inflammation, oxidative stress, and cellular senescence, respectively. The mRNA levels for biomarkers of liver fibrosis, inflammation, oxidative stress, and senescence-related genes were measured in liver tissues. Chromosomal stability was evaluated using global DNA methylation ELISA. Results: The ALT/AST ratio and liver to body weight ratio tended to increase in the DOX group, and Cr supplementation tended to attenuate this increase. Furthermore, elevated levels of liver fibrosis, inflammation, oxidative stress, and senescence were observed with DOX treatment, and Cr supplementation prior to DOX treatment ameliorated this hepatoxicity. Moreover, DOX treatment resulted in chromosomal instability (i.e., altered DNA methylation profile), and Cr supplementation showed a tendency to restore chromosomal stability with DOX treatment. Conclusion: The data suggest that Cr protected against DOX-induced hepatotoxicity by attenuating fibrosis, inflammation, oxidative stress, and senescence.


1996 ◽  
Vol 80 (3) ◽  
pp. 734-741 ◽  
Author(s):  
E. E. Dupont-Versteegden

The effects of exercise and the combination of exercise and clenbuterol on progression of muscular dystrophy were studied in mdx mice. At 3 wk of age, mdx mice were randomly assigned to sedentary (MS), exercise (ME), or combined exercise and clenbuterol (MEC) groups. Clenbuterol was given in the drinking water (1.0-1.5 mg . kg body weight-1 . day-1), and exercise consisted of spontaneous running activity on exercise wheels. At 3 mo or 1 yr of age, ventilatory function, contractile properties, and morphological characteristics of the soleus (Sol) and diaphragm (Dia) muscles were measured. The mdx mice receiving clenbuterol ran less than the mice without clenbuterol. The combination of clenbuterol and exercise was associated with an increase in Sol muscle weight and a muscle weight-to-body weight ratio of 30-35% compared with the sedentary group and approximately 20% compared to exercise alone. Myosin and total protein concentrations of the Sol and Dia increased in the MEC group at 1 yr of age only. Normalized active tension was increased in the Dia at 1 yr of age in both the ME and MEC groups by approximately 30%. Absolute tetanic tension of the Sol was increased at both 3 mo and 1 yr of age in the MEC compared with the MS group. At 1 yr of age, there was an additional 23% increase compared with the ME group. Fatigability increased in the MEC group by approximately 25% in the Sol and Dia muscles at both ages compared with the MS and ME groups. Results indicate that exercise and exercise plus clenbuterol decrease the progression of muscular dystrophy. However, different mechanisms may be involved because the combination of clenbuterol and exercise resulted in increased fatigability and the development of deformities, whereas exercise alone did not. Therefore, clenbuterol may not be suitable for use in patients with muscular dystrophy.


2016 ◽  
Vol 36 (9) ◽  
pp. 901-909 ◽  
Author(s):  
D Sheela ◽  
R Vijayaraghavan ◽  
S Senthilkumar

Buprenorphine drug cartridge was made for autoinjector device for use in emergency and critical situations to reduce the morbidity and mortality. Water-filled cartridges were prepared and buprenorphine was injected aseptically in the cartridge, to make 0.05 and 0.10 mg/mL. Rats were injected intraperitoneally, buprenorphine (0.3 and 0.6 mg/kg), repeatedly with the autoinjector and compared with manual injection (7 days and 14 days) using various haematological and biochemical parameters. No significant change was observed in the body weight, organ to body weight ratio and haematological variables in any of the experimental groups compared with the control group. Except serum urea and aspartate aminotransferase, no significant change was observed in glucose, cholesterol, triglycerides, bilirubin, protein, albumin, creatinine, uric acid, alanine aminotransferase, gamma glutamyltransferase and alkaline phosphatase. The autoinjectors deliver the drugs with spray effect and force for faster absorption. In the present study, the autoinjector meant for intramuscular injection was injected intraperitoneally in rats, and the drug was delivered with force on the vital organs. No significant difference was observed in the autoinjector group compared to the manual group showing tolerability and safety of the buphrenorphine autoinjector. This study shows that buprenorphine autoinjector can be considered for further research work.


2014 ◽  
Vol 38 (1) ◽  
pp. 74-82
Author(s):  
Wassan M. Hussen

The aim of the present study is to prepare ethanol extract of Pomegranate peel and the effects of this extract on testicular weight to body weight ratio, Serum cholesterol, testosterone concentration and histopathological changes of testes in rabbits treated with carbon tetrachloride (CCl4). Twenty four adult male rabbits were used. They were divided randomly into four equal groups. Animals were treated for 56 days as following: Rabbits of the 1st group were received 1 ml distal water orally once a day and olive oil 0.5 ml /kg B.W. I.P twice a week as control group. The second group were treated I.P with 500mg / kg B.W. of CCl4 mixing with equal volume of olive oil (0.5 ml/kg B.W.) twice a week (group T1). The third group was received pomegranate peel extract orally (100 mg/kg B.W) once a day and olive oil 0.5 ml /kg B.W. I.P twice a week (group T2). The fourth group were received pomegranate peel extract (100 mg/kg B.W) once a day oral I.P with 500 mg / kg B.W. of CCl4 mixing with equal volume of olive oil (o.5 ml/kg B.W.) twice a week (group T3). Blood samples were collected at (0, 14, 28, 42 and 56) days for measuring testosterone concentration, Serum cholesterol after treatments. Animals weighed and scarified and testis were removed and weighed, Samples of testis were taken for histopathological study. The results of the present study showed that treatment with pomegranate peel extract causes a significant (P>0.05) increase in testicular weight to body weight ratio. Also a significant (P>0.05) decreased of serum cholesterol and a significantly (P>0.05) elevation of testosterone concentration were observed. Histopathological examination of the testis was revealed that the extract of Pomegranate peel protect the testis against lesions caused by CCl4. In conclusion, Pomegranate peel extract could protect the tissue of testicles from CCl4 perhaps, by its anti-oxidative effect of pomegranate peel extract, hence eliminating the deleterious effects or toxic effect of CCl4.


Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Nadia S Bertoncello ◽  
Roseli P Moreira ◽  
Rodrigo Yokota ◽  
Rodolfo M Rosa ◽  
Danielle Y Arita ◽  
...  

The mechanisms underlying the link between high constitutive levels of ACE and diabetic nephropathy has not been completely understood, but an imbalance between angiotensin I (ACE) and II (ACE2) converting enzymes homeostasis has been described in diabetic kidney disease. The aim of this study was to evaluate ACE/ACE2 homeostasis in kidney from diabetic mice presenting increased dosage of ACE gene. Male mice (3 months old) genetically engineered to harbor one or three copies of the ACE gene were made diabetic (streptozotocin - STZ, 50 mg/Kg) and randomly assigned into: 1-copy control (1CC), 1-copy diabetic (1CD), 3-copy control (3CC) and 3-copy diabetic. At the end of experimental period body weight was evaluated and kidney was excised. Kidney-to-body weight ratio and ACE and ACE 2 activities were determined using specific substrates (ZPhe-HL and 7-Mca-APK(Dnp), respectively) (Two way ANOVA + Tukey test; P<0.05). Diabetes increased blood glucose (1CD : 436 ± 25 vs. 1CC: 90 ± 2; 3CD: 556 ± 6 vs. 3CC: 112 ± 4 mg/dL) and kidney-to-body weight ratio (1CD: 7.5 ± 0.2 vs. 1CC: 5.8 ± 0.2; 3CD: 7.8 ± 0.1 vs. 3CC: 5.8 ± 0.1 mg/g) with no influence of ACE genotype. As expected, renal ACE activity was directly related to ACE gene copy number in control group (3CC: 9.4 ± 2.11 vs. 1CC:5.6 ± 0.9 mU/mg protein). Renal ACE activity was decreased in diabetic groups (1CD: 3.6 ± 0.2 vs. 1CC: 5.6 ± 0.9; 3CD: 2.3 ± 0.4 vs. 3CC: 9.4 ± 2.1 mU/mg protein) with no influence of ACE genotype. Under physiological condition, renal ACE2 activity remained unchanged regardless of the ACE genotype (1CC: 1.9 ± 0.2 = 3CC: 1.4 ± 0.1 μM/min/mg). However upon a pathological stimulus, renal ACE2 activity was efficiently increased only in 1CD group, but not in 3CD, as compared with the others (1CD: 5.1 ± 0.9 vs. 1CC: 1.9 ± 0.2 = 3CC: 1.4 ± 0.1 = 3CD: 2.2 ± 0.2 μM/min/mg). Taken together, our results show for the first time, that susceptibility for the development of diabetic nephropathy associated with increased ACE gene dosage may be, at least in part, caused by a decrease on renal ACE2 activity. This may result in increased local levels of angiotensin II and decreased angiotensin (1-7), leading to altered glomerular permeability and albuminuria, functional alterations presented by 3CD animals. Financial Support: FAPESP, CAPES, CNPq.


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