scholarly journals Evaluation of optimal conditions for arginase activity in streptozotocin induced diabetic rats

2012 ◽  
Vol 50 (No. 2) ◽  
pp. 69-76 ◽  
Author(s):  
M. Erisir ◽  
E. Ercel ◽  
S. Yilmaz ◽  
S. Ozan
Keyword(s):  
Maximal Activity ◽  
Diabetic Rats ◽  
Arginase Activity ◽  
Female Rats ◽  
Kinetic Properties ◽  
Ph Profile ◽  
Optimum Ph ◽  
Liver And Kidney ◽  
And Control ◽  
Assay Conditions

The assay conditions needed to achieve maximal activity of liver and kidney arginase in diabetic and non-diabetic rats were investigated and compared. The physicochemical and kinetic properties of liver arginase in diabetic and control rats were very similar, those of kidney arginase were significantly different. It was found that preincubation temperature (68&deg;C), preincubation period (20 min), optimum pH (10.1) of liver arginase and K<sub>m</sub> (3.2) for its substrate, L-arginine, did not change in diabetic and non-diabetic rats. As a consequence of diabetes, the optimum Mn<sup>2+</sup> concentration for liver arginase only changed from 1 to 2 mM. Although the preincubation temperature and period for activation of kidney arginase in control rats was unnecessary, they were found to be 56&ordm;C and 12 min in diabetic rats. The pH profile of arginase in kidney of diabetic rats was different from that of control rats. The K<sub>m</sub> value (6.7) of arginase for L-arginine in kidney is unchanged in diabetes whereas a marked decrease in V<sub>max</sub> was found. Optimum Mn<sup>2+</sup> concentration (2 mM) for kidney arginase was unchanged in diabetes. The activity of arginase in liver of diabetic animals was higher 1.5 to 1.7 times than that of controls. Diabetes caused an about 53% decrease of arginase activity in kidney of female rats, 26% in that of males. These findings may suggest an idea that encoded arginases by separate gene loci may be affected differently by the pathological and hormonal status.

Insulin metabolism by liver, muscle, and kidneys from spontaneously diabetic rats

1986 ◽  
Vol 250 (5) ◽  
pp. E530-E537
Author(s):  
R. Rabkin ◽  
G. M. Reaven ◽  
C. E. Mondon
Keyword(s):  
Diabetic Rats ◽  
Insulin Clearance ◽  
Immunoreactive Insulin ◽  
Insulin Metabolism ◽  
Complex Process ◽  
Consistent Manner ◽  
Liver And Kidney ◽  
Spontaneously Diabetic Rats ◽  
And Control

The in vivo metabolism of insulin is a complex process in which liver, kidney, and muscle are major participants. In this study we evaluated the effect of spontaneous hyperglycemic nonketoacidotic diabetes (DH) and ketoacidotic diabetes (DKA) on insulin clearance and degradation by these organs. Livers, hindlimbs, and kidneys from nondiabetic controls and DH and DKA Bio-Breed rats were isolated and perfused with artificial media. Liver clearance of immunoreactive insulin (ml/min) was significantly higher in DH rats, 6.0 +/- 0.2, but significantly lower in DKA rats, 3.4 +/- 0.5, compared with controls, 4.6 +/- 0.2. Acidosis alone induced by ammonium chloride loading, did not impair liver insulin clearance (4.8 +/- 0.4 ml/min). Muscle responded differently to the diabetic state in that insulin clearance was not altered by DH and DKA. Renal (organ) clearance of insulin was significantly depressed in the DKA state when compared with controls (0.52 +/- 0.04 and 0.75 +/- 0.07 ml X min-1 X g-1, respectively). This could largely be explained by a lower glomerular filtration rate. Fractional urinary insulin clearance was increased twofold above control values in DH kidneys and fourfold in DKA kidneys, indicating that tubular luminal absorption of insulin was impaired in both states. By contrast contraluminal uptake (peritubular clearance) did not differ significantly from controls. 125I-insulin degrading activity of the 100,000 g supernate fraction from muscle homogenates was similar in the diabetic and control groups. However in liver and kidney, degrading activity did not correspond to whole organ insulin clearance in a consistent manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Sustained hyperglycemia results in testicular dysfunction and reduced fertility potential in BBWOR diabetic rats

1990 ◽  
Vol 259 (6) ◽  
pp. E881-E889 ◽  
Author(s):  
D. F. Cameron ◽  
J. Rountree ◽  
R. E. Schultz ◽  
D. Repetta ◽  
F. T. Murray
Keyword(s):  
Leydig Cells ◽  
Serum Testosterone ◽  
Diabetic Rats ◽  
Female Rats ◽  
Testicular Dysfunction ◽  
Structural Abnormalities ◽  
Fertility Potential ◽  
And Control ◽  
Blood Testis Barrier

Rats with short-term diabetes show a greater than 50% reduction of serum testosterone and increased lipid in Leydig cells but normal testicular structure. The purpose of this study was to determine the extent of testicular pathology (morphology index), integrity of the blood-testis barrier, daily sperm production (DSP), number of Leydig cells per testis (LC/T), and total trunk testosterone (TTT) in diabetic rats (BBWORdp) with long-term hyperglycemia (300-350 mg/dl for greater than 180 days) and to evaluate its effects on fertility potential. Results were compared with similarly aged normoglycemic rats (BBWORdr) and normal control Wistar rats. After 6 mo of diabetes, testis weights, DSPs, TTTs, and the morphology index were significantly reduced. The LC/T was not different from BBWORdr rats. The blood-testis barrier appeared intact, although structural abnormalities were noted in Sertoli-Sertoli junction complexes. There was a significant reduction in the number of pregnancies per rat and implantations per pregnancy in matings utilizing the diabetic BBWORdp rat and control Wistar female rats. Results indicate that long-term diabetes with sustained hyperglycemia leads to significant testicular dysfunction associated with decreased fertility potential.

Eudragit L-100 Capsules Aromatize and Quaternerize Chitosan for Insulin Nanoparticle Oral Delivery During Toxic Oxidative Stress in Rat Liver and Kidney

2020 ◽  
Vol 8 (3) ◽  
pp. 239-254 ◽  
Author(s):  
Reza Mahjub ◽  
Farzane K. Najafabadi ◽  
Narges Dehkhodaei ◽  
Nejat Kheiripour ◽  
Amir N. Ahmadabadi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oral Administration ◽  
Oral Delivery ◽  
Biochemical Parameters ◽  
Kidney Injury ◽  
Regular Insulin ◽  
Treated Group ◽  
Histopathological Change ◽  
Diabetic Rats ◽  
Liver And Kidney

Background: Insulin, like most peptides, is classified as a hydrophilic and macromolecular drug that is considered as a low permeable and unstable compound in the gastrointestinal (GI) tract. The acidic condition of the stomach can degrade insulin molecules. Moreover, the presence of proteolytic activities of some enzymes such as trypsin and chymotrypsin can hydrolyze amide-bonds between various amino-acids in the structures of peptides and proteins. However, due to its simplicity and high patient compliance, oral administration is the most preferred route of systemic drug delivery, and for the development of an oral delivery system, some obstacles in oral administration of peptides and proteins including low permeability and low stability of the proteins in GI should be overcome. Objective: In this study, the effects of orally insulin nanoparticles (INPs) prepared from quaternerized N-aryl derivatives of chitosan on the biochemical factors of the liver in diabetic rats were studied. Methods: INPs composed of methylated (amino benzyl) chitosan were prepared by the PEC method. Lyophilized INPs were filled in pre-clinical capsules, and the capsules were enteric-coated with Eudragit L100. Twenty Male Wistar rats were randomly divided into four groups: group1: normal control rats, group 2: diabetic rats, group 3: diabetic rats received capsules INPs(30 U/kg/day, orally), group 4: the diabetic rats received regular insulin (5 U/kg/day, subcutaneously). At the end of the treatment, serum, liver and kidney tissues were collected. Biochemical parameters in serum were measured using spectrophotometric methods. Also, oxidative stress was measured in plasma, liver and kidney. Histological studies were performed using H and E staining . Results: Biochemical parameters, and liver and kidney injury markers in serum of the diabetic rats that received INPs improved significantly compared with the diabetic group. INPs reduced oxidative toxic stress biomarkers in serum, liver and kidney of the diabetic treated group. Furthermore, a histopathological change was developed in the treated groups. Conclusion: Capsulated INPs can prevent diabetic liver and oxidative kidney damages (similar regular insulin). Therefore oral administration of INPs appears to be safe. Lay Summary: Although oral route is the most preferred route of administration, but oral delivery of peptides and proteins is still a challenging issue. Diabetes Mellitus may lead to severe complications, which most of them are life-threatening. In this study, we are testing the toxicity of oral insulin nanoparticles in kidney and liver of rats. For this investigation, we will prepare insulin nanoparticles composed of a quaternized derivative of chitosan. The nanoparticles will be administered orally to rats and the level of oxidative stress in their liver and kidney will be determined. The data will be compared to the subcutaneous injection of insulin.

scholarly journals Effects of a new thyrotropic drug isolated from Potentilla alba on the male reproductive system of rats and offspring development

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lubov V. Krepkova ◽  
Valentina V. Bortnikova ◽  
Aleksandra N. Babenko ◽  
Praskovya G. Mizina ◽  
Vladimir A. Mkhitarov ◽  
...  
Keyword(s):  
Animal Study ◽  
Male Fertility ◽  
Wistar Rats ◽  
Medical Condition ◽  
Adverse Outcomes ◽  
Female Rats ◽  
Childbearing Age ◽  
Offspring Development ◽  
Male Wistar Rats ◽  
And Control

Abstract Background The dysfunction of the thyroid gland is a common medical condition. Nowadays, patients frequently use medicinal herbs as complementary or alternative options to conventional drug treatments. These patients may benefit from treatment of thyroid dysfunctions with Potentilla alba L. preparations. While it has been reported that Potentilla alba preparations have low toxicity, nothing is known about their ability to affect reproductive functions in patients of childbearing age. Methods Male Wistar rats were orally treated with a thyrotrophic botanical drug, standardized Potentilla alba Dry Extract (PADE), at doses 8 and 40 times higher than the median therapeutic dose recommended for the clinical trials, for 60 consecutive days. Male Wistar rats receiving water (H2O) were used as controls. After completing treatment, half of the PADE-treated and control males were used to determine PADE gonadotoxicity, and the remaining half of PADE-treated and control males were mated with intact females. Two female rats were housed with one male for two estrus cycles. PADE effects on fertility and fetal/offspring development were evaluated. Results Herein, we report that oral treatment of male Wistar rats with PADE before mating with intact females instigated marked effects on male reproductive organs. Treatment significantly decreased the motility of the sperm and increased the number of pathological forms of spermatozoa. Additionally, a dose-dependent effect on Leydig cells was observed. However, these PADE effects did not significantly affect male fertility nor fetal and offspring development when PADE-treated males were mated with intact females. Conclusions PADE treatment of male rates negatively affected sperm and testicular Leydig cell morphology. However, these changes did not affect male fertility and offspring development. It is currently not known whether PADE treatment may affect human male fertility and offspring development. Therefore, these results from an animal study need to be confirmed in humans. Results from this animal study can be used to model the exposure-response relationship and adverse outcomes in humans.

Vasopressin V1 and V2 receptors in diabetes mellitus

1994 ◽  
Vol 266 (2) ◽  
pp. E217-E223 ◽  
Author(s):  
D. Trinder ◽  
P. A. Phillips ◽  
J. M. Stephenson ◽  
J. Risvanis ◽  
A. Aminian ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Inositol Phosphate ◽  
Free Water ◽  
Diabetic Rats ◽  
Biological Responses ◽  
Liver And Kidney ◽  
Streptozotocin Induced Diabetes ◽  
V2 Receptor ◽  
Plasma Arginine ◽  
Long Acting

Diabetes mellitus causes hypertonicity, increased plasma arginine vasopressin (AVP), polydipsia, and polyuria. Downregulation of AVP V2 receptors may contribute to the polyuria through diminished V2 receptor-mediated free water retention. After 2 wk of streptozotocin-induced diabetes mellitus, the diabetic rats had raised plasma glucose, AVP, and osmolality levels (P < 0.001) compared with nondiabetic controls (Sham). Insulin treatment (4 U long-acting insulin sc, daily) partially lowered these values (P < 0.01). There was a reduction in the number of renal and hepatic V1 receptors in the diabetic and diabetic+insulin animals compared with the sham animals (P < 0.05). The receptor affinity remained unchanged. In parallel, there was a reduction in maximum AVP-activated total inositol phosphate production in the liver and kidney of the diabetic and diabetic+insulin animals compared with the sham animals (P < 0.05). The density and affinity of renal V2 receptors and AVP-stimulated adenosine 3',5'-cyclic monophosphate production in the diabetic and diabetic+insulin animals were unchanged compared with the sham. These results demonstrate differential regulation of AVP receptors and suggest that downregulation of renal V2 receptors does not contribute to the polyuria of diabetes. In contrast, downregulation of V1 receptors might contribute to diminished V1 receptor-mediated biological responses to AVP seen in diabetes mellitus.

scholarly journals Characterization of a Solvent-Tolerant Amidohydrolase Involved in Natural Product Heterocycle Formation

Catalysts ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 892
Author(s):  
Lea Winand ◽  
Dustin Joshua Vollmann ◽  
Jacqueline Hentschel ◽  
Markus Nett
Keyword(s):  
Natural Product ◽  
Metal Ion ◽  
Building Blocks ◽  
Maximal Activity ◽  
Kinetic Properties ◽  
Pharmaceutical Drugs ◽  
Highly Active ◽  
Km Value ◽  
Amidohydrolase Superfamily ◽  
Solvent Tolerant

Heterocycles are important building blocks in pharmaceutical drugs and their enzymatic synthesis is attracting increasing interest. In recent years, various enzymes of the amidohydrolase superfamily were reported to catalyze heterocycle-forming condensation reactions. One of these enzymes, MxcM, is biochemically and kinetically characterized in this study. MxcM generates an imidazoline moiety in the biosynthesis of the natural product pseudochelin A, which features potent anti-inflammatory properties. The enzyme shows maximal activity at 50 °C and pH 10 as well as a kcat/Km value of 22,932 s−1 M−1 at its temperature optimum. Experimental data suggest that the activity of MxcM does not depend on a catalytic metal ion, which is uncommon among amidohydrolases. MxcM is highly active in diverse organic solvents and concentrated salt solutions. Furthermore, we show that MxcM is also capable to introduce imidazoline rings into derivatives of its natural substrate myxochelin B. Overall, MxcM is a solvent-stable, halotolerant enzyme with promising biochemical and kinetic properties and, in future, might become a valuable biocatalyst for the manufacturing of pharmaceutical drugs.

scholarly journals Transcutaneous CO2 application accelerates fracture repair in streptozotocin-induced type I diabetic rats

2020 ◽  
Vol 8 (2) ◽  
pp. e001129
Author(s):  
Takahiro Oda ◽  
Takahiro Niikura ◽  
Tomoaki Fukui ◽  
Keisuke Oe ◽  
Yu Kuroiwa ◽  
...  
Keyword(s):  
Endochondral Ossification ◽  
Callus Formation ◽  
Femoral Shaft ◽  
Shaft Fracture ◽  
Diabetic Rats ◽  
Fracture Repair ◽  
Female Rats ◽  
Control Group ◽  
Type I ◽  
Biomechanical Assessment

IntroductionDiabetes mellitus (DM) negatively affects fracture repair by inhibiting endochondral ossification, chondrogenesis, callus formation, and angiogenesis. We previously reported that transcutaneous CO2 application accelerates fracture repair by promoting endochondral ossification and angiogenesis. The present study aimed to determine whether CO2 treatment would promote fracture repair in cases with type I DM.Research design and methodsA closed femoral shaft fracture was induced in female rats with streptozotocin-induced type I DM. CO2 treatment was performed five times a week for the CO2 group. Sham treatment, where CO2 was replaced with air, was performed for the control group. Radiographic, histologic, genetic, and biomechanical measurements were taken at several time points.ResultsRadiographic assessment demonstrated that fracture repair was induced in the CO2 group. Histologically, accelerated endochondral ossification and capillary formation were observed in the CO2 group. Immunohistochemical assessment indicated that early postfracture proliferation of chondrocytes in callus was enhanced in the CO2 group. Genetic assessment results suggested that cartilage and bone formation, angiogenesis, and vasodilation were upregulated in the CO2 group. Biomechanical assessment revealed enhanced mechanical strength in the CO2 group.ConclusionsOur findings suggest that CO2 treatment accelerates fracture repair in type I DM rats. CO2 treatment could be an effective strategy for delayed fracture repair due to DM.

Sign in / Sign up

Export Citation Format

Share Document