Biomedical subjects

Andrzej Breborowicz

Publications and source records attributed to Andrzej Breborowicz.

At least 19 recordsLinked to original sources

PubMed2006

Peroxisome proliferator-activated receptor-gamma agonists diminish peritoneal functional and morphological changes induced by bioincompatible peritoneal dialysis solution.

BACKGROUND: To evaluate if peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists have a potential protective effect on the peritoneum changes induced by bioincompatible peritoneal dialysis (PD) solution in vivo. METHODS: Male Wistar rats were dialyzed three times daily for 28 days with 1.36% Dianeal (two groups: with (D+R) or without (D) rosiglitazone) or 1.36% Physioneal (two groups: with (P+R) or without (P) rosiglitazone). Peritoneal transport of fluid and small solutes was assessed. Nine rats that did not receive dialysis served as controls. RESULTS: Significant morphological changes were found in the D group compared with controls. Additional use of rosiglitazone in the D+R group resulted in less morphological changes and expression of collagen I as well as an increased drainage volume. The expression of VEGF was inhibited by rosiglitazone while no apparent effect was found regarding TGF/Smad pathway. CONCLUSIONS: The addition of rosiglitazone to standard dialysis fluids can maintain the peritoneal morphology and increase ultrafiltration in a PD rat model.

Animals↗

PubMed2006

Effect of peritoneal dialysis on renal morphology and function.

BACKGROUND: Results of clinical studies suggest that peritoneal dialysis (PD) is less harmful to the residual renal function than haemodialysis. However, we have no objective data describing the potential injuring effect of PD to kidney. We studied in rats after unilateral nephrectomy changes in renal structure and function after 12 weeks exposure to standard, glucose-based PD fluid. METHODS: One month after removing one kidney PD catheters were implanted in rats and during the following 12 weeks, twice a day, animals were infused with 20 ml of 3.9% glucose dialysis fluid containing high concentration of glucose degradation products. Rats not infused with the dialysis fluid served as control (CON). At the beginning and after 12 weeks of the study renal creatinine clearance, urinary excretion of albumin, N-acetyl-beta-glucosaminidase (NAG) and cytokines were measured. Concentration of malondialdehyde (MDA), advanced glycation end products (AGEs) and monocyte chemoattractant protein-1 (MCP-1) were measured in serum samples. Morphology of the kidneys was evaluated in the light microscope. RESULTS: After 12 weeks exposure to the dialysis fluid serum MDA, AGEs and MCP levels were increased as compared with CON by 80%, P < 0.002, 29%, P < 0.05 and 71%, P < 0.005, respectively. Renal clearance of creatinine was comparable in both groups, but urinary excretion of albumin was increased by 55% in control group and by 160% in the studied group, P < 0.001; whereas urinary excretion of NAG was not changed in control group but increased by 125% in the studied group, P < 0.01. Increase of the remnant kidney's weight was higher (+77%, P < 0.01) in the CON group, but accumulation of the extramesangial matrix in glomeruli and collagen in the peritubular space was stronger in the studied group by 69%, P < 0.0001 and 274%, P < 0.0001, respectively. CONCLUSION: Chronic exposure of rats to the glucose-based dialysis fluid causes morphological changes in the renal glomeruli similar to diabetic nephropathy. Albuminuria increases what may accelerate progression of the kidney damage.

Animals↗

PubMed2006

Effect of heparin on blood vascular endothelial growth factor levels in patients with ST-elevation acute myocardial infarction undergoing primary percutaneous coronary intervention.

It has been demonstrated that high blood vascular endothelial growth factor (VEGF) levels in patients with myocardial infarction decrease rapidly after reperfusion, possibly in response to heparin administration. We measured serum VEGF concentration before and after heparin infusion in 105 patients with ST-elevation acute myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI). Serum VEGF concentration in patients with STEMI was significantly higher than in healthy controls. After PCI, the concentration of VEGF decreased by approximately 70%, with the greatest decrease seen in patients with the highest initial VEGF levels. To determine whether heparin could decrease VEGF concentration by sequestering VEGF in the endothelium, a fixed dose of recombinant VEGF was incubated for 40 minutes with EA.hy926 endothelial cells in vitro. Recovery of VEGF from medium after culture was decreased by up to 15% with increasing doses of heparin. Concentration of VEGF did not change in the absence of heparin and/or endothelial cells. In conclusion, these results suggest that a rapid decrease in blood VEGF after PCI may be related to the administration of heparin, which binds simultaneously to VEGF and endothelial cells.

Adult↗

PubMed2006

Can an increased level of circulating IL-8 be a predictor of human longevity?

BACKGROUND: Interleukin-6 (IL-6) and IL-8 are considered to be potent inflammatory agents. However, IL-8 has also been reported to serve as an organ protective factor. The goal of our study was to compare the circulating levels of IL-8 and IL-6 in C-reactive protein (CRP)-negative subjects of different ages. MATERIAL/METHODS: Seventy subjects living in the Wielkopolska region were enrolled into the study and divided into three groups: group 1-30 young healthy subjects 21-37 years of age; group 2-30 healthy elderly individuals, age 65-87; group 3-10 centenarians (100-105 years). In all of these subjects, serum levels of IL-6 and IL-8 were assessed with an enzyme-linked immunosorbent assay. RESULTS: Concerning IL-6, both the serum concentration and the frequency of results above the sensitivity limit were comparable in all groups. With respect to IL-8, the frequency of results beyond the sensitivity limit in groups 1 and 2 did not differ significantly (5/30 and 8/30, respectively). By contrast, the majority of subjects from group 3 had an IL-8 level above the limit (9 out of 10; p<0.0001 vs. group 1 and p=0.0007 vs. group 2). In addition, the serum concentration of IL-8 in group 3 was higher than in both the other groups (p<0.01). Moreover, there was a positive correlation between the age of analysed subjects and their level of IL-8 (r=0.450; p<0.0001). CONCLUSIONS: It seems possible that an association of an increased serum level of IL-8 and a low level of IL-6 is related to longevity.

Adult↗

PubMed2006

Iron sucrose induced morphological and functional changes in the rat kidney.

Treatment of anemia in uremic patients requires simultaneous supplementation of erythropoietin and iron. Because of the impaired iron absorption from the gastrointestinal tract in conditions of renal insufficiency, intravenous supplementation is a treatment of choice in such conditions. Iron compounds used for intravenous supplementation induce several systemic side effects, and therefore, we studied the effect of chronic exposure to iron sucrose in rats on renal function. Experiments were performed on male Wistar rats, which were infused intraperitoneally every 4 days, for 28 days with iron sucrose in a dose 1 mg/kg bw or 10 mg/kg bw diluted in 20 mL of the dialysis fluid. Control animals were infused with plain dialysis fluid. Renal function was evaluated at the beginning and at the end of the study. Additionally morphology of the kidneys was evaluated in all animals after 28 days of the study. Chronic exposure of rats to iron sucrose resulted in increased accumulation of PAS-positive material in their glomeruli: + 38% at Fe 1 mg/kg bw P < 0.05 and + 42% at Fe 10 mg/kg/bw P < 0.01 and collagen in the peritubular area: + 40% at Fe 1 mg/kg bw P < 0.005 and + 77% at Fe 10 mg/kg/bw P < 0.001. Only renal clearance of urea was decreased by 53%, P < 0.01 in rats exposed to iron sucrose at a dose of 10 mg/kg bw. Chronic exposure of rats to iron sucrose results in morphologic changes of the kidney; however, mild impairment in renal function was observed only at the highest (10 mg Fe/kg bw) concentration of iron sucrose.

Albuminuria↗

PubMed2006

Flow index evaluation of 3-D volume flow images: an in vivo and in vitro study.

Three-dimensional (3-D) ultrasound imaging has improved evaluation of organ circulation and might contribute new information on maternal and fetal blood supply. Flow index (FI) of 3-D color images has been proposed as a measure of perfusion. The aim of this study was to evaluate whether the 3-D FI is a parameter of volume flow and flow velocity in a human vessel and in a flow phantom. A 1-cm-long strip of the uterine artery was recorded in 3-D power Doppler (3D-PD) mode in a cross-sectional study of 170 normal singleton pregnancies between 26 and 42 weeks' gestation. A fixed ultrasound system installation was used during the examination. The VOCAL software integrated in the ultrasound unit calculated vessel volume and FI. Reproducibility of the measurements was tested. The method was also tested on a commercially available flow phantom. Reproducibility measurements gave satisfactory results, both in terms of inter- and intraobserver variation. Unexpectedly, in normal pregnancy, the uterine artery FI decreased slightly with gestation. Uterine artery vessel volume increased, however, with gestational age. A poor correlation was found between the FI and both flow velocity and volume flow in the flow phantom. In conclusion, 3D-PD imaging can give impressive anatomical pictures of organ vascular tree. However, the new FI is poorly related to flow velocity or volume of flow.

Arteries↗

PubMed2006

Effects of glutathione supplementation during peritoneal dialysis.

We examined the effect of L-2-oxothiazolidine-4-carboxylate (OTZ) on peritoneal morphology and function of mesothelial cells in rats during peritoneal dialysis (PD). We implanted intraperitoneal catheters into 14 rats and injected the rats twice daily for 4 weeks with standard PD fluid (group C, control; n = 7) or PD fluid supplemented with OTZ 1 mmol/L (group OTZ; n = 7). At the beginning and the end of the study, we collected samples of 4-hour dwell effluents from every rat under sterile conditions. We used those samples to test, in ex vivo conditions, the effect on primary cultures of rat peritoneal mesothelial cells with regard to synthesis of total protein and collagen in mesothelium. After 4 weeks, the rats were humanely killed, and glutathione peroxidase activity in erythrocytes was measured. Morphologic analysis of the peritoneal membrane was also performed. As compared with group OTZ, group C showed intraperitoneal adhesions that were more severe, a higher density of mesothelial cells, a higher density of peritoneal vessels, similar peritoneal thickness, lower activity of glutathione peroxidase, and greater ability of their dialysate effluent to induce synthesis of total proteins and collagen in cultured mesothelial cells. Relationships between various parameters were analyzed. We conclude that OTZ preserves peritoneal morphology and the function of mesothelial cells during PD.

Animals↗

PubMed2005

Early loss of proliferative potential of human peritoneal mesothelial cells in culture: the role of p16INK4a-mediated premature senescence.

Much has been learned about the mechanisms underlying cellular senescence. The pathways leading to senescence appear to vary, depending on the cell type and cell culture conditions. In this respect, little is known about senescence of human peritoneal mesothelial cells (HPMC). Previous studies have significantly differed in the reported proliferative lifespan of HPMC. Therefore, in the present study, we have examined how HPMC enter state of senescence under conditions typically used for HPMC culture. HPMC were isolated from omentum and grown into senescence. The cultures were assessed for the growth rate, the presence of senescence markers, activation of cell-cycle inhibitors, and the oxidative stress. HPMC were found to reach, on average, six population doublings before senescence. The terminal growth arrest was associated with decreased expression of Ki67 antigen, increased percentage of cells in the G1 phase, reduced early population doubling level cDNA-1 mRNA expression, and the presence of senescence-associated beta-galactosidase. Compared with early-passage cells, the late-passage HPMC exhibited increased expression of p16INK4a but not of p21Cip1. In addition, these cells generated more reactive oxygen species and displayed increased presence of oxidatively modified DNA (8-hydroxy-2'-deoxyguanosine). These results demonstrate that early onset of senescence in omentum-derived HPMC may be associated with oxidative stress-induced upregulation of p16INK4a.

Blotting, Western↗

PubMed2005

Limitations of CA125 as an index of peritoneal mesothelial cell mass.

BACKGROUND: CA125 is commonly used as an index of the mesothelial cell mass in patients treated with peritoneal dialysis. However, we have no data that show a direct relationship between the number of mesothelial cells, their functional properties, and the amount of CA125 produced in these cells. METHODS: Experiments were performed on primary in vitro cultures of human peritoneal mesothelial cells obtained from 32 donors of various ages and of both sexes. Spontaneous release of CA125 from the confluent mesothelial cells was measured and correlated with the number of cells in monolayers and with their functional properties. We also studied acute effects of cytokines (IL-1beta, TNF-alpha, and INF-gamma) and the chronic effects of glucose (45 mM) on the CA125 content in mesothelial cells and the release of this antigen from their cytosol. RESULTS: Cells from older donors released more CA125, but we found no correlation between the number of cells and the amount of CA125 released from their cytosol. The synthesis of CA125 in mesothelial cells does not correlate with the amount of monocyte chemoattractant protein 1 or interleukin-6 produced in these cells. Acute exposure to cytokines did not modify CA125 content or its release from mesothelial cells. Chronic exposure of mesothelial cells for 4 weeks to glucose (45 mM) decreased the CA125 content of their cytosol and the release of this antigen into the culture medium. Mannitol, at the same concentration and under the same conditions, did not produce these effects, namely a decrease in the CA125 content in the cytosol or its release into the cultural medium. CONCLUSIONS: The amount of CA125 released from mesothelial cells is not a good index of their number or their functional properties, because the CA125 release depends not only on the number of cells, but also on their properties. Furthermore, the process is affected by the age of the cell donor and environmental factors such as a high glucose content. The results of this study show the limitations of CA125 as an index of the mesothelial cell mass and viability.

Adult↗

PubMed2005

Glucose degradation products (GDP's) and peritoneal changes in patients on chronic peritoneal dialysis: will new dialysis solutions prevent these changes?

As peritonitis rates are declining, the rate of technique failure due to ultrafiltration failure and inadequate solute removal is becoming more important. The failure of the peritoneal membrane to provide adequate dialysis increases with longer duration on PD and correlates with the structural changes in the peritoneal membrane. The exact mechanism responsible for these structural changes is unclear. Conventional PD fluids with glucose as the osmotic agent and more importantly the glucose degradation products (GDP) generated during the heat sterilization of these solutions seems to be responsible for inducing many of these changes in the peritoneum. GDP's in addition to causing structural and functional alterations of the peritoneal cells is also a leading cause of advanced glycation end-products (AGE) production. There is evidence to suggest that the GDP's and AGE's are not limited to the peritoneal cavity and the membrane. They have been shown to get deposited in the vascular walls. In addition they also interact with receptors on endothelial cells and smooth muscle. Thus they could contribute to the vascular dysfunction similar to that seen in diabetes. Formation of GDP's can be reduced and even be avoided with the use of newer "biocompatible" solutions by sterilizing the glucose and the buffer in separate chambers. These newer solutions have been shown to have several local and systemic advantages over the conventional PD solutions. It remains to be seen whether their chronic use from the start of peritoneal dialysis will prevent the development of peritoneal damage thus allowing these patients to remain on this modality for longer periods.

Animals↗

PubMed2005

[Hematologic parameters in Polish centenarians].

We undertook this study to characterize the haematological indices in centenarian subjects who should be an excellent group to study the mechanisms of physiological aging. This study is a part of the Polish Centenarians Program co-ordinated by the International Institute of Molecular and Cell Biology in Warsaw. We examined 89 subjects aged 100 to 111 (14 males and 75 females). Mean values of all haematological parameters were within the normal range in females. In males, haemoglobin level (Hb), red blood cell count (RBC) and hematocrit (Hct) were slightly lower than WHO references (12.7 +/- 1.3 g/dl, 4.10 +/- 0.48 M/ml and 38.4 +/- 3.8%, respectively). However, anaemia was more frequent in females than in males (57.1% vs 29.1%, p < 0.05). In females with anaemia there was a tendency to decrease its severity with age. In the oldest group (aged 105-111 years) Hb and Hct had a tendency for lower values vs the youngest group (100-101 years) (10.1 +/- 1.8 g/dl vs 11.6 +/- 0.1 g/dl, p = 0.067 and 30.9 +/- 5.0% vs 35.0 +/- 0.3%, p = 0.067). Additionally, in the youngest group there were three females with severe anaemia (Hb < 9.0 g/dl) whereas in the oldest group all females with anaemia had Hb above 11.0 g/dl. In males the analysis was not undertaken because of small group of studied subjects. In conclusion, anaemia seems to be a relatively common problem in studied centenarians. Severe anaemia seems to be an eliminating factor in centenarian women.

Age Factors↗

PubMed2005

Is normal saline harmful to the peritoneum?

BACKGROUND: Normal saline (0.9% NaCl) is used during various abdominal surgical interventions and during peritoneal dialysis to rinse the peritoneal cavity. Although no clear clinical evidence exists for the bioincompatibility of normal saline, various experimental studies have suggested that 0.9% NaCl solution can initiate fibrosis of peritoneum. MATERIAL AND METHODS: We review the data derived from in vitro and in vivo experimental studies demonstrating the cytotoxic effect of 0.9% NaCl and its ability to initiate peritoneal adhesions. RESULTS: Normal saline reduces the viability and fibrinolytic activity of peritoneal mesothelial cells. Use of normal saline to wash the peritoneal cavity during abdominal operations or after chronic peritoneal dialysis is more likely to produce adhesions than is no irrigation at all. Chronic exposure of the peritoneum to normal saline causes overgrowth of the connective tissue and formation of new blood vessels within that tissue. CONCLUSION: Normal saline is a bioincompatible solution that predisposes to the formation of peritoneal adhesions and fibrosis of the peritoneum. A 0.9% NaCl solution should therefore not be used to rinse the peritoneal cavity after interruption of peritoneal dialysis.

Animals↗

PubMed2004

L-2-oxothiazolidine-4-carboxylic acid reduces in vitro cytotoxicity of glucose degradation products.

BACKGROUND: Glucose degradation products (GDP) are an important factor that contribute to bioincompatibility of peritoneal dialysis fluids. These substances are generated in the dialysis fluid during heat sterilization. Several approaches have been proposed to reduce the content or toxicity, or both, of GDP present in the dialysis fluid. We examined whether L-2-oxothiazolidine-4-carboxylic acid (OTZ), a precursor for glutathione synthesis, reduces the cytotoxicity of GDP in human peritoneal mesothelial cells. METHODS: Experiments were performed on primary mesothelial cell cultures. Free radical generation in these cells after exposure to acetaldehyde (ACT), glyoxal (GLYO) or methylglyoxal (M-GLYO) was detected with a fluorescent probe. Cell viability measurements were based on release of LDH from cell cytosol, and synthesis of IL-6 and proliferation after exposure to GDP. Effects of individual GDPs and of dialysis fluid free of GDP (GDP-free PDF) or containing GDP (GDP-high PDF) on cell viability were also studied in the presence of OTZ (1 mmol/l). RESULTS: All of the GDPs as well as the autoclaved dialysis fluid caused increased free radical generation. ACT increased LDH release from the cells by 374% (P < 0.001), and this effect was abolished by OTZ. All of the GDPs inhibited cell growth (ACT, 47%, P < 0.01; GLYO, 52%, P < 0.01; M-GLYO, 26%, P < 0.05) and this effect was reversed in presence of OTZ. ACT inhibited Il-6 synthesis in mesothelial cells by 74% P < 0.01 and this effect was prevented by OTZ. GDP-high PDF but not GDP-free PDF reduced synthesis of IL-6 in mesothelial cells by 40% (P < 0.01) an effect that was reversed by OTZ. Mesothelial cell growth was more strongly inhibited by GDP-high PDF (76%, P < 0.01) than by GDP-free PDF (31%, P < 0.05). OTZ improved growth of mesothelial cells in the presence of GDP-high PDF (+150%, P < 0.01) and in presence of GDP-low PDF (+38%, P < 0.05). OTZ prevented the cytotoxic effect of GDP-high PDF on mesothelial cells. CONCLUSIONS: The GDP-induced stimulation of free radicals in mesothelial cells in the present study may provide a possible mechanism of GDP cytotoxicity. Because OTZ reduced the toxic effects of GDP on mesothelial cells, this compound may improve biocompatibility of peritoneal dialysis fluids.

Cell Division↗

PubMed2004

Effect of hyaluronan-supplemented dialysate on in vitro function of human peritoneal mesothelial cells.

BACKGROUND: Addition of hyaluronan (HA) to the dialysis solution has been suggested as a means to protect the peritoneum from injury during peritoneal dialysis (PD). METHODS: Concentrations of inflammatory mediators were determined in dialysate samples obtained from PD patients after 6-hour dwells with glucose-based (13.6 g/l) solution containing 0.1 and 0.5 g/l of exogenous high-molecular-weight HA. We additionally evaluated the effect of HA-supplemented dialysate, drained after dwell in PD patients, on function of human peritoneal mesothelial cells (MC) in in vitro culture. RESULTS: Concentration of nitrites was significantly higher in HA 0.5 g/l supplemented dialysate (+43%, p < 0.05) as compared to control. Levels of monocyte chemoattractant protein (MCP-1), soluble intercellular adhesive molecule (s-ICAM), vascular endothelial growth factor (VEGF) and fibronectin were comparable in all the studied groups. However, when MC were exposed in in vitro conditions for 24 h to the studied dialysates, we observed that HA containing fluids inhibited the synthesis of MCP-1, s-ICAM, VEGF and fibronectin in these cells. HA-supplemented dialysate accelerated growth rate of in vitro proliferating MC. CONCLUSION: High-molecular-weight HA added to the dialysis fluid exerts anti-inflammatory and antifibrotic actions on the in vitro cultured MC and accelerates their growth rate what may be important for peritoneal healing during PD.

Cells, Cultured↗

PubMed2004

Reproducibility of the measurements of creatinine clearance in patients with a stable renal function.

In everyday practice the measurement of creatinine clearance (CCr) is used for the evaluation of the renal function. Since large body of evidence points to the inaccuracy of this test, we decided to check whether a repeated measurement of CCr might improve the assessment of the glomerular filtration rate. The study comprised 233 subjects, 105 females and 128 males, aged 22-80 years (mean age: 50.8 +/- 12.8 years) with the history of renal stones and a stable renal function, e.g. without changes in plasma creatinine. In every patient CCr was measured twice. Thereafter, all studied subjects were sorted by the increasing absolute values of the difference between two measurements of CCr e.g. as the difference between two measurements of CCr with omitted sign (absDCCr). Then, they were divided into 3 groups corresponding to the tertiles of absDCCr (tertile = 1/3). When the two values of CCr were compared among all patients, the mean difference between them (DCCr) was only 1.51 +/- 26.86 ml/min. The values of the individual DCCr varied, however, from -122.2. ml/min to 69.3 ml/min. As far as sex, age and height were concerned, there were no differences between the groups. However, weight was lower in group A (first tertile) vs. group B (second tertile) (p < 0.05). Also, BMI was lower in the group A vs. both group B and C (p < 0.05 and p < 0.01; respectively). In conclusion, our study points out to a poor reproducibility of the measurements of CCr in non-hospitalized subjects, especially in those with the high BMI.

Adult↗

PubMed2004

Peritoneal dialysis with solutions low in glucose degradation products is associated with improved biocompatibility profile towards peritoneal mesothelial cells.

BACKGROUND: In vitro experiments point to a better biocompatibility profile of new pH-neutral peritoneal dialysis fluids (PDFs) containing low levels of glucose degradation products (GDPs). The present study examines the impact on human peritoneal mesothelial cells (HPMCs) of equilibrated dialysates obtained during dialysis with either conventional or new PDFs. METHODS: Peritoneal dialysate was collected from 17 patients participating in a randomized, controlled, cross-over trial comparing a pH-neutral low-GDP solution (Balance) to a conventional solution (S-PDF). All patients were treated sequentially for 3 months with both PDFs. At the end of each treatment phase, peritoneal effluent was drained after a timed 10 h dwell. Samples of dialysate were then mixed with standard culture medium and added to in vitro cultures of HPMCs from healthy donors. Cells were assessed for proliferation, viability and cytokine release. RESULTS: Proliferation and viability of HPMCs were better preserved in the presence of effluent obtained during dialysis with Balance (P<0.046 and P<0.035, respectively). The proliferative response of HPMCs correlated with the concentration of fibronectin in dialysates (P = 0.0024). Effluent drained following a 3 month dialysis with Balance contained significantly increased levels of fibronectin (P = 0.004) and CA125 antigen (P = 0.0004) compared with S-PDF. There was no significant difference in constitutive and stimulated cytokine (IL-6, MCP-1, VEGF) synthesis by HPMCs treated with either Balance- or S-PDF-derived effluents. CONCLUSIONS: These results suggest that therapy with new pH-neutral low-GDP solutions contribute to an intraperitoneal milieu that improves mesothelial cell proliferation and viability. It may positively impact on the preservation of the peritoneal membrane integrity during long-term dialysis.

Adult↗

PubMed2004

Intraperitoneal enalapril ameliorates morphologic changes induced by hypertonic peritoneal dialysis solutions in rat peritoneum.

Peritoneal fibrosis (PF) is one of the most serious causes of technique failure in long-term peritoneal dialysis (PD). Although the mechanisms responsible for the genesis of PF are not well understood, angiotensin II is known to promote fibrosis and inflammation in various tissues and angiotensin converting enzyme inhibitors (ACEIs) have been shown to attenuate those effects. We previously showed that ACEIs have beneficial effects on peritoneal alterations induced by hypertonic (3.86% glucose) PD solutions. In the present study, we investigated the local effects of intraperitoneal (IP) enalapril on peritoneal alterations induced by 3.86% glucose PD solution in rats on chronic PD. One week after peritoneal catheter insertion, 23 non uremic male rats were randomly divided into two groups: group A (n = 11) received 20 mL 3.86% PD solution twice daily, and group B (n = 12) received 20 mL 3.86% PD solution containing 1 mg/L enalapril twice daily. After 4 weeks of such infusions, we measured net ultrafiltration (UF) volume and obtained samples of visceral peritoneum from the liver for thickness measurement. Net UF was significantly higher (6.6 +/- 0.2 mL vs. 5.6 +/- 0.2 mL) and peritoneal thickness was significantly lower (30 +/- 5 microm vs. 52 +/- 0.8 microm) in group B. We conclude that intraperitoneal enalapril (an ACEI) protects the peritoneal membrane from the effects of hypertonic glucose. This protection might be mediated by enalapril's interference with angiotensin though inhibition of cytokine overexpression.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2003

Glucose-induced changes in the phenotype of human peritoneal mesothelial cells: effect of L-2-oxothiazolidine carboxylic acid.

BACKGROUND: During peritoneal dialysis, mesothelial cells are chronically exposed to high concentrations of glucose. Therefore, the cytotoxic effect of glucose may alter the function and reactivity of these cells. METHODS: For 4 weeks, human peritoneal mesothelial cells were cultured in vitroin medium supplemented with 45 mM glucose or 45 mM mannitol or with 45 mM glucose and 1 mM L-2-oxothiazolidine-4-carboxylic acid (OTZ), the latter being a precursor for glutathione synthesis. Peroxidation of the mesothelial cell lipids, synthetic activity and reaction of these cells to peritoneal dialysis fluids were studied. RESULTS: In contrast to mannitol, glucose enhanced the peroxidation of the cellular lipids (+65%, p < 0.01) an effect that was prevented by OTZ. Synthesis of hyaluronan and vascular endothelial growth factor was reduced in mesothelial cells treated with glucose by 36% (p < 0.01) and 44% (p < 0.05), respectively; both glucose effects were reversed when cells were incubated with glucose plus OTZ. Monocyte chemoattractant protein-1 synthesis by cells exposed to glucose was increased by 31% (p < 001), and again that effect was prevented by OTZ. Glucose and mannitol stimulated synthesis of fibronectin (+32%, p < 0.05). Mesothelial cells chronically exposed to glucose became activated after subsequent exposure to the dialysis fluid, as reflected by the increased release of interleukin (IL)-6, in contrast to control mesothelial cells, in which IL-6 synthesis was suppressed. CONCLUSIONS: Chronic exposure of mesothelial cells to glucose changes their synthetic activity and their reaction after exposure to dialysis fluids. Some of these effects are prevented by OTZ, which suggests that glucose-induced free radicals are responsible for a change in mesothelial cell phenotype under the conditions of peritoneal dialysis.

Carrier Proteins↗