Structural and Functional Alterations of the Peritoneum after Prolonged Exposure to Dialysis Solutions: Role of Aminoguanidine

2001 ◽  
Vol 21 (3) ◽  
pp. 245-253 ◽  
Author(s):  
Eun Ah Lee ◽  
Jong Hoon Oh ◽  
Hyun Ah Lee ◽  
Sung Il Kim ◽  
Eung Woo Park ◽  
...  
Keyword(s):  
High Glucose ◽  
Peritoneal Fluid ◽  
Absorption Rate ◽  
Prolonged Exposure ◽  
Control Group ◽  
Fluid Absorption ◽  
Plasma Urea ◽  
Capillary Formation ◽  
Vascular Walls

Objective The effect of long-term use of high glucose dialysate on peritoneal structure and function, and its relation with accumulation of advanced glycosylation end-product (AGE) in the peritoneum was investigated in this study. Methods Dialysates with 4.25% glucose were injected into the peritoneal cavity of normal rats for 12 weeks without (PD, n = 7) and with (1 g/L, PD+AG, n = 7) aminoguanidine in their drinking water. Rats not having intraperitoneal (IP) injection served as control ( n = 9). After 12 weeks of IP injection, a 2-hour peritoneal equilibration test (PET) was performed using 30 mL 4.25% glucose dialysate. Intraperitoneal volume (IPV), dialysate-to-plasma urea ratio at 2 hours (D2/P2), the ratio of dialysate glucose at 2 hours to initial dialysate glucose (D2/D0), and the peritoneal fluid absorption rate (Qa) were evaluated. After the PET, samples of the parietal peritoneum were taken for hematoxylin and eosin (H&E) staining and immunohistochemical staining for AGE. Results The IPV and D2/D0 glucose were significantly lower and Qa and D2/P2 urea significantly higher in the PD group than in the control group. Aminoguanidine reversed in part the changes in IPV and D2/P2 urea in the PD group; it had no effect on Qa and D2/D0 glucose. The H&E staining showed a linear mesothelial lining with negligible cells and capillaries in the narrow submesothelial space in the control group. Mesothelial denudation and submesothelial infiltration of monocytes and capillary formation were observed in the PD group. Mesothelial denudation was relatively intact in the PD+AG group compared with the PD group. Submesothelial monocyte infiltration and capillary formation in the PD+AG group were not as prominent as in the PD group. Positive AGE staining was found in the submesothelial space, vascular walls, and endomysium in the PD group, while it was markedly attenuated in PD+AG group and negligible in the control group. Conclusion Long-term use of high glucose solutions induced peritoneal AGE accumulation and mesothelial denudation, and increased peritoneal permeability and peritoneal fluid absorption rate. Inhibition of peritoneal AGE accumulation prevented those functional and structural damages to the peritoneum.

Peritoneal Transport of Glucose in Rat

1999 ◽  
Vol 19 (5) ◽  
pp. 442-450 ◽  
Author(s):  
Min Sun Park ◽  
Eun Young Lee ◽  
Gyo Il Suh ◽  
Jacek Waniewski ◽  
Andrzej Werynski ◽  
...  
Keyword(s):  
Glucose Transport ◽  
High Glucose ◽  
Peritoneal Fluid ◽  
Absorption Rate ◽  
Convective Transport ◽  
Control Group ◽  
Fluid Absorption ◽  
Sprague Dawley ◽  
High Insulin ◽  
Group 2

Objective To evaluate the convective transport characteristics of glucose and the effect of high glucose and insulin during experimental peritoneal dialysis in rat. Methods Male Sprague–Dawley rats weighing 300 – 400 g were used in this study. Mannitol (5%) was used as osmotic agent. Glucose was added to dialysis solution to yield a concentration of 100 mg/dL (group 1) or 300 mg/dL (group 2). Mannitol solution (5%) containing the same concentration of electrolytes and lactate but without glucose was used as control (group 3). In group 2, blood sugar was maintained at approximately 300 mg/dL by continuous intravenous infusion of 25% glucose solution and 0.9% NaCl solution. A 2-hour dwell study was performed with 30 mL of test solutions. Intraperitoneal volume was calculated by volume marker (18.5 kBq of 131I-human radioiodinated serum albumin, RISA) dilution with corrections made for the elimination of RISA from the peritoneal cavity (KE) and sample volume. The diffusive mass transport coefficient (KBD) and sieving coefficient (SBRF) were calculated by using the Babb–Randerson–Farrell model. S was also calculated directly by using isocratic methods (SI). The peritoneal fluid absorption rate (KE) was taken into account for the calculation of SI. Results Intraperitoneal volume was significantly higher in group 2 compared with groups 1 and 3. Peritoneal fluid absorption rate, KE, was similar in all three groups. SBRF and SI for glucose were significantly lower in group 2 compared with groups 1 and 3. SBRF for glucose in group 2 was below zero and SI near zero. KBD for glucose was significantly higher in group 2 than in groups 1 and 3. Plasma and dialysate concentrations of insulin increased during the initial hour and then decreased to the baseline value in groups 1 and 3, while in group 2 it continuously increased. Conclusion Significantly lower sieving coefficients for glucose in the high glucose and high insulin group suggest that transport mechanisms other than simple passive transport are involved in peritoneal glucose transport, and that high glucose per se and/or high insulin may be important factors that determine glucose transport characteristics.

Effects of Bicarbonate/Lactate Solution on Peritoneal Advanced Glycosylation End-Product Accumulation

2000 ◽  
Vol 20 (5_suppl) ◽  
pp. 33-38 ◽  
Author(s):  
Min Sun Park ◽  
Jin Kook Kim ◽  
Cliff Holmes ◽  
and Miriam F. Weiss
Keyword(s):  
Peritoneal Cavity ◽  
High Glucose ◽  
Parietal Peritoneum ◽  
Control Group ◽  
Normal Male ◽  
Plasma Urea ◽  
Conventional Solution ◽  
Dialysis Solutions ◽  
Advanced Glycosylation

Advanced glycosylation end-products (AGEs) are associated with diabetic complications and peritoneal damage after long-term peritoneal dialysis (PD) with high glucose dialysis solutions. Glucose degradation products (GDPs) derived during heat sterilization of high glucose dialysis solutions are thought to accelerate AGE formation. A new technique of separating glucose from electrolytes has yielded markedly lower GDP levels and permitted the use of dialysis solutions containing the physiologic buffer bicarbonate. Formation of AGEs in vitro with this new solution is significantly lower compared with formation of AGEs with conventional solutions. The purpose of the present study was to investigate the effect of long-term intraperitoneal use of new, neutral dialysis solution (B/L) containing bicarbonate (25 mmol/L) and lactate (15 mmol/L) on peritoneal AGE accumulation and permeability. Normal male Sprague–Dawley rats were used. Twice daily for 12 weeks, 30 mL of new solution (B/L) or conventional solution [Lac (lactate 40 mmol/L)] was injected into the peritoneal cavity of the test rats. As a control, rats that were not injected were kept for 12 weeks in the same manner as the test rats. After 12 weeks, a 2-hour peritoneal equilibration test (PET) was performed in the test rats. After the PET, the parietal peritoneum and liver were obtained for evaluation of peritoneal morphology and for immunohistochemistry for AGE. Intensity of AGE staining was semi-quantitatively graded from 0 to 3. The omentum was also obtained and immediately frozen for analysis of pentosidine content by high-performance liquid chromatography. Compared with findings in the control group, hematoxylin and eosin staining of the parietal peritoneum and liver samples revealed partial denudation of mesothelial cells in the Lac group; denudation was not remarkable in the B/L group. The B/L solution showed significantly less AGE staining in the peritoneal cavity compared to conventional solution. However, B/L solution failed to lower pentosidine levels. Intraperitoneal volume and the ratio of dialysate glucose at 2 hours to dialysate glucose at instillation (D2/D0 glucose) were significantly lower and the ratio of dialysate urea to plasma urea at 2 hours (D2/P2 urea) was significantly higher in the Lac and B/L groups than in the control group. Intra-peritoneal volume was significantly higher in the B/L group than in the Lac group; D2/D0 glucose and D2/P2 urea did not differ between the two groups. In conclusion, peritoneal ultrafiltration decreased after long-term PD. The B/L solution showed a small but statistically significant protective effect against decreasing ultrafiltration as compared with Lac solution. The B/L solution attenuated peritoneal AGE accumulation compared with conventional solution, but did not affect peritoneal pentosidine levels. These findings indicate that biochemical kinetics of various AGE peptides are not unique, but multivalent.

Hyaluronan Preserves Peritoneal Membrane Transport Properties

2001 ◽  
Vol 21 (2) ◽  
pp. 136-143 ◽  
Author(s):  
Qun-Ying Guo ◽  
Wen-Xing Peng ◽  
Hui-Hong Cheng ◽  
Ren-Gao Ye ◽  
Bengt Lindholm ◽  
...  
Keyword(s):  
Membrane Transport ◽  
Peritoneal Fluid ◽  
Absorption Rate ◽  
Control Group ◽  
Fluid Absorption ◽  
Peritoneal Membrane ◽  
Lymphatic Absorption ◽  
Dialysis Solution ◽  
Significant Difference ◽  
And Control

Background We have shown that intraperitoneal (IP) addition of hyaluronan (HA) in a single dwell study in rat could increase peritoneal fluid removal by decreasing the peritoneal fluid absorption rate. In this study, we investigated the impact of repeated use of HA on peritoneal membrane transport characteristics. Methods Twelve male Sprague–Dawley rats received a once-daily IP injection of 25 mL 4.25% glucose dialysis solution without (HP group, n = 6) or with 0.025% HA (HA group, n = 6) for 1 week. Forty-eight hours after the last injection, a 4 hour dwell using 25 mL 4.25% glucose dialysis solution with IP volume marker and frequent dialysate and blood samplings was performed in each rat as well as in rats that did not receive any injection (control group, n = 8). Results Although the IP volumes were significantly lower in the HP and HA groups compared to the control group, IP volume in the HA group was significantly higher than in the HP group. Net ultrafiltration at 4 hours was 5.6 ± 1.3 mL, 10.2 ± 1.8 mL, and 13.2 ± 0.6 mL for the H P, HA, and control group, respectively. The peritoneal fluid absorption rate decreased by 45% in the HA group compared to the HP group. There was no significant difference in peritoneal fluid absorption rate between the HA and the control group. No difference was found in the direct lymphatic absorption rate between the HP and HA groups [0.010 ± 0.003 mL/minute in the HP group and 0.011 ± 0.004 mL/min in the HA group] although they were both higher than that of the control group (0.004 ± 0.001 mL/min). The solute transport rates were in general significantly higher in the HP group compared to the HA and control groups, and there was no significant difference between the latter two groups, except that protein transport rate was significantly lower in the HA group compared to the control group. Conclusions The present study suggests that ( 1 ) repeated exposure to hypertonic glucose-based dialysis solution results in increased peritoneal solute transport rates, as well as increased peritoneal fluid absorption rates; and ( 2 ) these changes, reflecting a highly permeable peritoneal membrane, were ameliorated by repeated IP addition of hyaluronan. The similar changes in the direct lymphatic absorption rate in rats that received daily IP injection of dialysis solution suggest that direct peritoneal lymphatic absorption was not influenced by hyaluronan.

Intraperitoneal Addition of Hyaluronan Improves Peritoneal Dialysis Efficiency

1999 ◽  
Vol 19 (2_suppl) ◽  
pp. 106-111 ◽  
Author(s):  
Tao Wang ◽  
Hui-Hong Cheng ◽  
Olof Heimbürger ◽  
Chi Chen ◽  
Jacek Waniewski ◽  
...  
Keyword(s):  
Peritoneal Fluid ◽  
Absorption Rate ◽  
Glucose Solution ◽  
Control Group ◽  
Fluid Absorption ◽  
High Concentration ◽  
Control Groups ◽  
Fluid Removal ◽  
Molecular Weights ◽  
Fill Volume

Background It has been shown that hyaluronan (HA) can decrease peritoneal fluid absorption. It is not known, however, how various molecular weights and various concentrations of hyaluronan affect peritoneal fluid absorption rate. Methods A study of 4-hour dwells, with frequent dialysate and blood sampling, was performed in male SpragueCawley rats (6 7 rats in each group) with 1311 albumin as an intraperitoneal volume marker. Each rat was infused intraperitoneally with 25 mL of 1.5% glucose solution alone or 1.5% glucose solution containing hyaluronan at various molecular weights (MW -85 kC, 280 kC, 500 kC, and 4 MC) or containing hyaluronan of MW 500 kC at various concentrations (0.01%,0.05%,0.1%,0.5%). Two additional groups were infused with 40 mL of 1.36% glucose dialysate alone or 1.36% glucose dialysate with 0.01 % hyaluronan (MW 500 kC) to test the effect of hyaluronan when high dialysate fill volume was used. Results Addition of 0.01% hyaluronan significantly decreased peritoneal fluid absorption rate (KE) (by 22%, p < 0.01). The decrease was more marked with hyaluronan at high MW or high concentration, or with high dialysate fill volume. The net ultrafiltration tended to be higher in all hyaluronan groups compared to their control groups except in the 4 MC group; this difference was mainly due to a lower KE in all the hyaluronan groups. The direct lymphatic flow was significantly decreased in the 0.5% HA group. The transcapillary ultrafiltration rate (au) was significantly lower in the 4 MC group as compared to the control group. No difference in au was found between the other groups as compared to their control groups. Conclusions (1) Intraperitoneal addition of hyaluronan may increase net peritoneal fluid removal, mainly because hyaluronan decreases peritoneal fluid absorption rate. The decrease was more marked when high dialysate fill volume was used, indicating that intraperitoneal addition of hyaluronan can prevent the decreased net ultrafiltration caused by an increase in dialysate fill volume. (2) The decrease in peritoneal fluid absorption rate may be both MW-dependent and concentration-dependent: that is, a higher MW as well as a higher concentration of hyaluronan result in a more marked decrease in peritoneal fluid absorption rate. (3) Low concentrations of high MW hyaluronan may also decrease au. However, au did not decrease when high concentrations of hyaluronan were used despite a significant decrease in peritoneal fluid absorption rate.

scholarly journals Hyaluronan decreases peritoneal fluid absorption in peritoneal dialysis.

1997 ◽  
Vol 8 (12) ◽  
pp. 1915-1920
Author(s):  
T Wang ◽  
C Chen ◽  
O Heimbürger ◽  
J Waniewski ◽  
J Bergström ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Peritoneal Fluid ◽  
Protein Transport ◽  
Intraperitoneal Administration ◽  
Control Group ◽  
Fluid Absorption ◽  
Sprague Dawley ◽  
Transfer Coefficients ◽  
Fluid Removal ◽  
Dialysis Solution

Hyaluronan, exhibiting a high resistance against water flow, acts in the tissue as a barrier against rapid changes in water content. To test whether hyaluronan has any effect on the peritoneal fluid and solute transport, and, in particular, on the peritoneal fluid absorption, a 4-h dwell study with an intraperitoneal volume marker (radiolabeled human serum albumin [RISA]) was conducted in 21 male Sprague Dawley rats (three groups, seven rats in each group). Each rat was injected intraperitoneally with 25 ml of 1.36% glucose solution alone (control group), with 0.005% hyaluronan (HA1 group), or with 0.01% hyaluronan (HA2 group). Dialysate and blood samples were taken frequently for analyses of fluid and solute (urea, glucose, and protein) transport. The intraperitoneal volume was calculated from the dilution of RISA with a correction for RISA disappearance from the peritoneal cavity. This study shows that adding hyaluronan to peritoneal dialysis solution significantly (P < 0.01) increased the net peritoneal fluid removal, mainly due to a significant decrease in the peritoneal fluid absorption rate (P < 0.01). The diffusive mass transfer coefficients for glucose, urea, and protein did not differ between the three groups. The peritoneal clearance of urea increased significantly in the two hyaluronan groups compared with the control group, due to the increased net fluid removal in the hyaluronan groups. These results suggest that intraperitoneal administration of hyaluronan during a single peritoneal dialysis exchange may significantly increase the peritoneal fluid and solute removal by decreasing peritoneal fluid absorption.

Peritoneal Fluid and Solute Transport with Different Polyglucose Formulations

1998 ◽  
Vol 18 (2) ◽  
pp. 193-203 ◽  
Author(s):  
Tao Wang ◽  
Olof Heimbürger ◽  
Hui-Hong Cheng ◽  
Jonas Bergström ◽  
Bengt Lindholm
Keyword(s):  
Solute Transport ◽  
Peritoneal Cavity ◽  
Peritoneal Fluid ◽  
Absorption Rate ◽  
Glucose Solution ◽  
Ex Vivo ◽  
Elimination Rate ◽  
Fluid Absorption ◽  
Significant Difference ◽  
Glucose Polymer

Objective To study peritoneal fluid and solute transport characteristics using different polyglucose solutions with and without the addition of glucose. Design Thirty-one rats were divided into three groups. A 4-hour dwell study with frequent dialysate and blood samples was performed in each rat using 25 mL of 7.5% polyglucose solution (PG, n = 11),7.5% polyglucose + 0.35% glucose solution (PG1, n = 12), or 3.75% polyglucose + 1.93% glucose solution (PG2, n = 8). Radiolabeled human albumin (RISA) was added to the solutions as an intraperitoneal volume (IPV) marker. In addition, polyglucose degradation was evaluated ex vivo over 24 hours. Experimental Animals Thirty-one male Sprague Dawley rats (300 g) were used. Main Outcome Measures Fluid and solute (glucose, urea, sodium, potassium, and total protein) transport characteristics as well as changes in dialysate osmolality were evaluated. Results The IPV was higher in the PG1 and PG2 groups than in the PG group during the first 2 hours of the dwell. The IPV, in fact, decreased during the first hour of the dwell in the PG group. However, the net ultrafiltration at 4 hours tended to be lower in the PG2 (3.2 ± 1.5 mL) group compared to the PG (5.1 ± 2.3 mL) and the PG1 groups (5.2 ± 2.1 mL) (p = 0.07), and no significant difference was found between the PG and PG1 groups. Adding glucose to the PG solution increased the RISA elimination rate (KE, representing the fluid absorption rate from the peritoneal cavity): 25.5 ± 8.2, 37.5 ± 12.2, and 42.5 ± 8.9 μL/ min for the PG, PG1, and the PG2 group, respectively, p < 0.01. Dialysate osmolality (Dos) increased with the dwell time in the PG and PG1 groups but decreased in the PG2 group. The increase in Dos was partially due to the degradation of glucose polymer, which was supported by the marked increase in osmolality over 24 hours of incubation of PG solution with peritoneal fluid, ex vivo. The diffusive mass transport coefficient for the investigated solutes did not differ among the three groups (except for glucose, which was significantly lower in the PG group). The sieving coefficient for sodium was significantly higher in the PG group compared to the PG1 group (p < 0.05). Conclusion Our results suggest that, although there was an initial decrease in the intraperitoneal dialysate volume, significant amounts of fluid can be removed by polyglucose solution during a single 4-hour dwell in rats, despite the low osmolality of the solution. The positive fluid removal induced by the PG solution is partially due to the lower fluid absorption rate associated with this solution and may, to some extent, also be due to the degradation of glucose polymer within the peritoneal cavity, resulting in increased dialysate osmolality. The addition of glucose to the polyglucose solution does not seem to improve ultrafiltration in a 4-hour dwell in the rat model. However, the peritoneal fluid absorption rate may be increased, and peritoneal transport of glucose and sodium may be altered, by adding glucose to the polyglucose solution.

scholarly journals Threefold Peritoneal Test of Osmotic Conductance, Ultrafiltration Efficiency, and Fluid Absorption

2013 ◽  
Vol 33 (4) ◽  
pp. 419-425 ◽  
Author(s):  
Jacek Waniewski ◽  
Ramón Paniagua ◽  
Joanna Stachowska–Pietka ◽  
María-de-Jesús Ventura ◽  
Marcela Ávila–Díaz ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Solute Transport ◽  
Peritoneal Fluid ◽  
Absorption Rate ◽  
Transport Parameter ◽  
Fluid Absorption ◽  
Transport Parameters ◽  
Fluid Removal ◽  
Modifiable Factors ◽  
Small Solute

BackgroundFluid removal during peritoneal dialysis depends on modifiable factors such as tonicity of dialysis fluids and intrinsic characteristics of the peritoneal transport barrier and the osmotic agent—for example, osmotic conductance, ultrafiltration efficiency, and peritoneal fluid absorption. The latter parameters cannot be derived from tests of the small-solute transport rate. We here propose a simple test that may provide information about those parameters.MethodsVolumes and glucose concentrations of drained dialysate obtained with 3 different combinations of glucose-based dialysis fluid (3 exchanges of 1.36% glucose during the day and 1 overnight exchange of either 1.36%, 2.27%, or 3.86% glucose) were measured in 83 continuous ambulatory peritoneal dialysis (CAPD) patients. Linear regression analyses of daily net ultrafiltration in relation to the average dialysate-to-plasma concentration gradient of glucose allowed for an estimation of the osmotic conductance of glucose and the peritoneal fluid absorption rate, and net ultrafiltration in relation to glucose absorption allowed for an estimation of the ultrafiltration effectiveness of glucose.ResultsThe osmotic conductance of glucose was 0.067 ± 0.042 (milliliters per minute divided by millimoles per milliliter), the ultrafiltration effectiveness of glucose was 16.77 ± 7.97 mL/g of absorbed glucose, and the peritoneal fluid absorption rate was 0.94 ± 0.97 mL/min (if estimated concomitantly with osmotic conductance) or 0.93 ± 0.75 mL/min (if estimated concomitantly with ultrafiltration effectiveness). These fluid transport parameters were independent of small-solute transport characteristics, but proportional to total body water estimated by bioimpedance.ConclusionsBy varying the glucose concentration in 1 of 4 daily exchanges, osmotic conductance, ultrafiltration efficiency, and peritoneal fluid absorption could be estimated in CAPD patients, yielding transport parameter values that were similar to those obtained by other, more sophisticated, methods.

scholarly journals Histopathological comparison of the salivary glands’ acini and striated ducts after experimental prolonged daily administration of oral ubiquinone doses in rats

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Ali Ghanim Abdullah ◽  
Ban Ismael Sedeeq ◽  
Marwan Saad Azzubaidi
Keyword(s):  
Salivary Glands ◽  
Prolonged Exposure ◽  
Oral Treatment ◽  
Underlying Mechanism ◽  
Treated Group ◽  
Control Group ◽  
Albino Rats ◽  
Excessive Salivation ◽  
The Difference

Abstract Also called coenzyme Q10 (CoQ10), Ubiquinone is a vitamin-like endogenously produced factor essential for Adenosine triphosphate (ATP) mitochondrial production. Several research studies have reported that the exogenous supplementation of CoQ10 can lead to excessive salivation, especially in patients complaining of dry mouth. The objective of this study was to investigate the effect of long-term daily use of CoQ10 on the salivary glands in experimental animals by comparing the diameters of the glandular acini and striated ducts of a CoQ10-treated group and a control group. Twenty-five white albino rats were randomly divided into two groups; the control group consisted of 10 rats, while the CoQ10-treated group comprised 15 rats. The latter received daily oral treatment of 300 mg/kg CoQ10 for six weeks. Samples of the parotid, submandibular and sublingual glands were then dissected and examined histologically for comparative measurement of the diameters of the glands’ acini and striated ducts. The CoQ10 treated group had mean diameters of the serous acini for the parotid (79.8±11.2 μm) and submandibular (81.07±13.5 μm) glands that were significantly higher (P<0.05) than their diameters in the control group (67.5±8.4 μm and 73.3±13.8 μm), respectively. However, the difference was not statistically significant when comparing the diameters of striated ducts of the CoQ10-treated group and the control group. Continuous and prolonged exposure to exogenous ubiquinone may cause hypertrophic dilation of the acini within the salivary glands, namely the parotid and submandibular glands, which might be the underlying mechanism for excessive salivation. This can be considered a reversible adaptive response.

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