scholarly journals The metabolic fate of intravenously injected peptide-bound chondroitin sulphate in the rat

1976 ◽  
Vol 158 (1) ◽  
pp. 39-46 ◽  
Author(s):  
K M Wood ◽  
C G Curtis ◽  
G M Powell ◽  
F S Wusteman

The degradation of intravenously administered chondroitin sulphate-peptide, obtained by trypsin digestion of rat cartilage preparations labelled in vitro with 35S (and, in some cases, with 3H), was studied in rats. As with free chains of chondroitin sulphate, the major site of accumulation and degradation in the body was the liver, although peptide-linked chains were taken up more rapidly than free chains. In the first 2h after intravenous injection of a chondroitin sulphate-peptide fraction, labelled macromolecular components were excreted in the urine. These were shown to be chondroitin sulphate-peptide of the same degree of sulphation but of smaller average size than the injected material. A similar observation was made when free chains of chondroitin sulphate from the same source were administered intravenously. An isolated perfused rat kidney failed to de-sulphate circulating chondroitin sulphate-peptide, but a component of lower average molecular weight was excreted in the urine. When a chondroitin sulphate-peptide fraction of relatively larger hydrodynamic volume was administered, very little chondroitin sulphate appeared in the urine in the first 2h. It was concluded that, depending on size and/or peptide content, the chondroitin sulphate-peptide released from connective tissues into the circulation would probably be subjected to one of two alternative fates. The smaller fragments are more likely to be excreted in the urine, whereas the larger ones are taken up by the liver and there degraded to inorganic sulphate and undefined carbohydrate components.

1959 ◽  
Vol 197 (5) ◽  
pp. 1128-1130 ◽  
Author(s):  
John F. Thomson ◽  
Florence J. Klipfel

Kidney slices from rats in which one-third of the body water was replaced by D2O showed no impairment of the capacity to accumulate PAH, despite the moribund condition of the animals. In vitro, 100% D2O inhibited PAH uptake by 65%, oxygen consumption by only 15%, during a 1-hour incubation of kidney slices; very little PAH was taken up after the first 30 minutes.


1999 ◽  
Vol 18 (12) ◽  
pp. 713-717 ◽  
Author(s):  
J-G Zhang ◽  
M Viale ◽  
M Esposito ◽  
W E Lindup

1 Tiopronim (N-(2-mercaptopropionyl)-glycine) is a drug with a free thiol (sulphydryl) group that is used clinically. We have reported previously that tiopronin protects rat kidney slices in vitro from the nephrotoxic effects of cisplatin and does not reduce the antitumour activity of cisplatin. Tiopronin has been investigated therefore for its protective effects in rats in vivo. 2 The extent of kidney damage was studied 5 days after the administration of cisplatin. A single injection (i.p.) of cisplatin (6 mg/kg; 20,umollkg) to female Wistar albino rats caused a sustained decrease in body weight and, after 5 days, plasma urea, creatinine and kidney weight were increased. Tiopronin (2.5 mmol/kg, p.o.) ameliorated cisplatin nephrotoxicity when given 1 h before cisplatin. Tiopronin provided marked protection against cisplatin-induced increases in urea (from 237+19 mg to 48+23 mg/100 ml; control: 17+1) and creatinine (from 6.5+0.5 to 1.7+0.5 mg/100 ml control: 1.0 + 0.1). Tiopronin did not, prevent the body weight loss caused by cisplatin. In addition, an intraperitoneal dose (1 mmol/lkg) oftiopronin afforded similar protection to that of an oral dose. Rats that received an i.p. mixture of cisplatin (6 mg/kg) and tiopronin (65 mg/kg) displayed generally less toxicity, as indicated by a small fall in body weight and smaller increases in urea and creatinine and kidney weight. 3 The results show that tiopronin protects against cisplatin-induced nephrotoxicity. Oral administration of tiopronin may be a clinically useful way to prevent cisplatin nephrotoxicity.


1969 ◽  
Vol 113 (3) ◽  
pp. 543-549 ◽  
Author(s):  
H. C. Robinson

1. Whole tissue preparations and subcellular fractions from embryonic chicken cartilage were used to measure the rate of incorporation of inorganic sulphate into chondroitin sulphate in vitro. 2. In cartilage from 14-day-old embryos, [35S]sulphate is incorporated to an equal extent into chondroitin 4-sulphate and chondroitin 6-sulphate at a rate of 1·5nmoles of sulphate/hr./mg. dry wt. of cartilage. 3. Microsomal and soluble enzyme preparations from embryonic cartilage catalyse the transfer of sulphate from adenosine 3′-phosphate 5′-sulphatophosphate into both chondroitin 4-sulphate and chondroitin 6-sulphate. 4. The effects of pH, ionic strength, adenosine 3′-phosphate 5′-sulphatophosphate concentration and acceptor chondroitin sulphate concentration on the soluble sulphotransferase activity were examined. These factors all influence the activity of the sulphotransferase, and pH and incubation time also influence the percentage of chondroitin 4-sulphate formed.


2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Xiang Li ◽  
Si Chen ◽  
Jing-En Li ◽  
Ning Wang ◽  
Xin Liu ◽  
...  

The study was designed to investigate the chemical composition and antioxidant activities of polysaccharides from Yingshan Cloud Mist Tea. The chemical composition of green tea polysaccharides (GTPS) was analyzed by Fourier-transform infrared (FT-IR) spectroscopy, scanning electron microscope (SEM), thermogravimetric (TGA), gas chromatograph (GC), and high-performance gel-permeation chromatography (HPGPC). Then, the antioxidant activities in vitro of GTPS, effects of GTPS on body weight, and the antioxidant activities in chickens were studied. The results showed that GTPS were composed of rhamnose (Rha), arabinose (Ara), xylose (Xyl), mannose (Man), glucose (Glu), and galactose (Gal) in a molar ratio of 11.4 : 26.1 : 1.9 : 3.0 : 30.7 : 26.8 and the average molecular weight was 9.69×104 Da. Furthermore, GTPS exhibited obvious capacity of scavenging DPPH radical, hydroxyl radical, and superoxide radical and enhanced the ferric-reducing power in vitro. Last, GTPS significantly increased the body weight of chickens, enhanced the T-AOC, SOD, and GSH-Px level, and decreased the content of MDA in chickens. The results indicated that GTPS might be a kind of natural antioxidant, which had the potential application in feed industry.


1973 ◽  
Vol 134 (4) ◽  
pp. 1009-1013 ◽  
Author(s):  
Keith M. Wood ◽  
Frederick S. Wusteman ◽  
C. Gerald Curtis

The degradation of chondroitin 4-[35S]sulphate isolated from chick-embryo cartilage was studied in the rat by experiments on free-range animals, on wholly anaesthetized animals with ureter cannulae, by perfusion of isolated liver, by whole-body radioautography and by isolation of liver lysosomes. After injection into rats 68% of the radioactivity was recovered in the urine after 24h, approximately one-half of this being in the form of low-molecular-weight material, chiefly inorganic sulphate. Cannulation experiments demonstrated that the proportion of low-molecular-weight components excreted in the urine increased with time until, after 12h, virtually all was inorganic sulphate. Whole-body radioautography identified the liver as the major site of radioisotope accumulation after injection of labelled polysaccharide. Perfusion through isolated liver indicated that this organ has the ability to metabolize the polymer with the release of low-molecular-weight products, principally inorganic sulphate. Incubation of a lysosomal fraction prepared from rat liver after injection of chondroitin 4-[35S]sulphate gave rise to degradation products of low molecular weight, and experiments in vitro with rat liver lysosomes confirmed that these organelles are capable of the entire degradative process from chondroitin sulphate to free inorganic sulphate.


1977 ◽  
Vol 166 (3) ◽  
pp. 373-379 ◽  
Author(s):  
Martin A. Perry ◽  
Gillian M. Powell ◽  
Frederick S. Wusteman ◽  
C. Gerald Curtis

The metabolic fate of heparan N-[35S]sulphate was studied in rats. Heparan sulphate was obtained from either bovine aorta or lung and labelled with 35S by desulphation and subsequent resulphation in vitro. Experiments in which heparan N-[35S]sulphate was administered intravenously to either free-range or wholly anaesthetized rats with ureter cannulae established that substantial desulphation occurs in vivo, with elimination of inorganic [35S]sulphate in urine. Oligosaccharides labelled with 35S, possible intermediates in heparan sulphate degradation, could not be detected in urine or blood. The general distribution of radioactivity after administration of heparan N-[35S]sulphate, as demonstrated by whole-body radioautography, suggested that desulphation was not restricted to one organ in particular. Support for this view was obtained in experiments in which heparan N-[35S]sulphate was administered to animals after the removal of kidneys, liver, spleen, pancreas or gastrointestinal tract. In all cases inorganic [35S]sulphate was still produced. The ability of rats of desulphate heparan N-[35S]sulphate was progressively impaired by increasing concentrations of heparin administered simultaneously. It was concluded that heparan sulphate is metabolized at a number of sites in the body by a sequence of degradative events leading to the formation of inorganic sulphate. It is also concluded that at least some of these events are common to heparan sulphate and heparin.


Author(s):  
S.K. Aggarwal

The proposed primary mechanism of action of the anticancer drug cisplatin (Cis-DDP) is through its interaction with DNA, mostly through DNA intrastrand cross-links or DNA interstrand cross-links. DNA repair mechanisms can circumvent this arrest thus permitting replication and transcription to proceed. Various membrane transport enzymes have also been demonstrated to be effected by cisplatin. Glycoprotein alkaline phosphatase was looked at in the proximal tubule cells before and after cisplatin both in vivo and in vitro for its inactivation or its removal from the membrane using light and electron microscopy.Outbred male Swiss Webster (Crl: (WI) BR) rats weighing 150-250g were given ip injections of cisplatin (7mg/kg). Animals were killed on day 3 and day 5. Thick slices (20-50.um) of kidney tissue from treated and untreated animals were fixed in 1% buffered glutaraldehyde and 1% formaldehyde (0.05 M cacodylate buffer, pH 7.3) for 30 min at 4°C. Alkaline phosphatase activity and carbohydrates were demonstrated according to methods described earlier.


2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.


1976 ◽  
Vol 15 (05) ◽  
pp. 248-253
Author(s):  
A. K. Basu ◽  
S. K. Guha ◽  
B. N. Tandon ◽  
M. M. Gupta ◽  
M. ML. Rehani

SummaryThe conventional radioisotope scanner has been used as a whole body counter. The background index of the system is 10.9 counts per minute per ml of sodium iodide crystal. The sensitivity and derived sensitivity parameters have been evaluated and found to be suitable for clinical studies. The optimum parameters for a single detector at two positions above the lying subject have been obtained. It has been found that for the case of 131I measurement it is possible to assay a source located at any point in the body with coefficient of variation less than 5%. To add to the versatility, a fixed geometry for in-vitro counting of large samples has been obtained. The retention values obtained by the whole body counter have been found to correlate with those obtained by in-vitro assay of urine and stool after intravenous administration of 51Cr-albumin.


Author(s):  
Mohammed Ibrahim ◽  
Alaa Zaky ◽  
Mohsen Afouna ◽  
Ahmed Samy

Carrier erythrocytes are emerging as one of the most promising biological drug delivery systems investigated in recent decades. Beside its biocompatibility, biodegradability and ability to circulate throughout the body, it has the ability to perform extended release system of the drug for a long period. The ultimate goal of this study is to introduce a new carrier system for Salbutamol, maintaining suitable blood levels for a long time, as atrial to resolve the problems of nocturnal asthma medication Therefore in this work we study the effect of time, temperature as well as concentration on the loading of salbutamol in human erythrocytes to be used as systemic sustained release delivery system for this drug. After the loading process is performed the carrier erythrocytes were physically and cellulary characterized. Also, the in vitro release of salbutamol from carrier erythrocytes was studied over time interval. From the results it was found that, human erythrocytes have been successfully loaded with salbutamol using endocytosis method either at 25 Co or at 37 Co . The highest loaded amount was 3.5 mg/ml and 6.5 mg/ml respectively. Moreover, the percent of cells recovery is 90.7± 1.64%. Hematological parameters and osmotic fragility behavior of salbutamol loaded erythrocytes were similar that of native erythrocytes. Scanning electron microscopy demonstrated that the salbutamol loaded cells has moderate change in the morphology. Salbutamol releasing from carrier cell was 43% after 36 hours in phosphate buffer saline. The releasing pattern of the drug from loaded erythrocytes showed initial burst release in the first hour followed by a very slow release, obeying zero order kinetics. It concluded that salbutamol is successfully entrapped into erythrocytes with acceptable loading parameters and moderate morphological changes, this suggesting that erythrocytes can be used as prolonged release carrier for salbutamol.


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