Can N-Acetylcysteine Preserve Peritoneal Function and Morphology in Encapsulating Peritoneal Sclerosis?

2009 ◽  
Vol 29 (2_suppl) ◽  
pp. 202-205 ◽  
Author(s):  
Devrim Bozkurt ◽  
Ender Hur ◽  
Burcu Ulkuden ◽  
Murat Sezak ◽  
Hasim Nar ◽  
...  

Long-term use of the peritoneum as a dialysis membrane results in progressive irreversible dysfunction, described as peritoneal fibrosis. Oxidative stress during peritoneal dialysis has been established in many studies. Generation of reactive oxygen species (ROS) by conventional peritoneal dialysis solutions, regardless of whether produced by high glucose, angiotensin II, or glucose degradation products may be responsible for progressive membrane dysfunction. The well-known antioxidant molecule N-acetylcysteine (NAC) is capable of direct scavenging of ROS. The aim of the present study was to investigate the effect of NAC therapy on both progression and regression of encapsulating peritoneal sclerosis (EPS). We divided 49 nonuremic Wistar albino rats into four groups: Control group—2 mL isotonic saline intraperitoneally (IP) daily for 3 weeks; CG group—2 mL/200 g 0.1% chlorhexidine gluconate (CG) and 15% ethanol dissolved in saline injected IP daily for a total of 3 weeks; Resting group—CG (weeks 1 – 3), plus peritoneal resting (weeks 4 – 6); NAC-R group—CG (weeks 1 – 3), plus 2 g/L NAC (weeks 4 – 6). At the end of the experiment, all rats underwent a 1-hour peritoneal equilibration test with 25 mL 3.86% PD solution. Dialysate-to-plasma ratio (D/P) urea, dialysate white blood cell count (per cubic milliliter), ultrafiltration (UF) volume, and morphology changes of parietal peritoneum were examined. The CG group progressed to encapsulating peritoneal sclerosis, characterized by loss of UF, increased peritoneal thickness, inflammation, and ultimately, development of fibrosis. Resting produced advantages only in dialysate cell count; with regard to vascularity and dialysate cell count, NAC was more effective than was peritoneal rest. Interestingly, we observed no beneficial effects of NAC on fibrosis. That finding may be a result of our experimental severe peritoneal injury model. However, decreased inflammation and vascularity with NAC therapy were promising results in regard to membrane protection.

2008 ◽  
Vol 28 (5_suppl) ◽  
pp. 53-57 ◽  
Author(s):  
Devrim Bozkurt ◽  
Selahattin Bicak ◽  
Savas Sipahi ◽  
Huseyin Taskin ◽  
Ender Hur ◽  
...  

Background Encapsulating peritoneal sclerosis (EPS) is an infrequent but extremely serious complication of long-term peritoneal dialysis. Fibrosis of the submesothelial compact zone and neoangiogenesis underlie the pathophysiology of EPS. Colchicine is a well-known anti-inflammatory and antifibrotic agent that has been used for some fibrosing clinical states, such as liver fibrosis. Objective To determine the antifibrotic and anti-inflammatory effects of colchicine in an EPS rat model in both progression (P) and regression (R). Methods 48 nonuremic albino Wistar rats were divided into 5 groups: control group, 2 mL isotonic saline intraperitoneally (IP) daily for 3 weeks; CG group, IP injection of 2 mL/200 g chlorhexidine gluconate (CG) (0.1%) and ethanol (15%) dissolved in saline, daily for 3 weeks; resting group, CG (0 – 3 weeks) + peritoneal resting (4 – 6 weeks); C-R group, CG (0 – 3 weeks) + 1 mg/L colchicine (4 – 6 weeks); C-P group, CG (0 – 3 weeks) + 1 mg/L colchicine in drinking water (0 – 3 weeks). At the end, a 1-hour peritoneal equilibration test was performed with 25 mL 3.86% peritoneal dialysis solution. Dialysate-to-plasma ratio of urea (D/P urea), dialysate WBC count, ultrafiltration volume, and morphological changes of parietal peritoneum were examined. Result Exposure to CG for 3 weeks resulted in alterations in peritoneal transport (increased D/P urea, decreased ultrafiltration volume; p < 0.05) and morphology (increased inflammation, neovascularization, fibrosis, and peritoneal thickness; p < 0.05). Resting had some beneficial effects on peritoneal derangements; however, once the peritoneum had been stimulated, resting alone was not enough to reverse these pathological changes. Colchicine had more pronounced effects on membrane integrity via decreased inflammation, cell infiltration, and vascularity compared to the resting group. Conclusion We suggest that colchicine may have therapeutic value in the management of EPS.


2020 ◽  
pp. 096032712096604
Author(s):  
Mehmet Asi Oktan ◽  
Cihan Heybeli ◽  
Cemre Ural ◽  
Ayse Kocak ◽  
Gokcen Bilici ◽  
...  

Colistin methanesulfonate (CMS), a clinical form of colistin, is widely used as a last-line treatment for multidrug-resistant (MDR) gram-negative bacterial infections in critically ill patients presenting a considerably high mortality rate. However, nephrotoxicity is considered to be a critical adverse effect that limits CMS’s clinical use. Alpha-lipoic acid (ALA) is a strong antioxidant that is effective in preventing nephrotoxicity in many models. The aim of this study was to investigate ALA’s ability to protect against nephrotoxicity induced by colistin in rats. Male Wistar albino rats were randomly divided into four groups. Group 1 was the control group (Control; n = 6), in which isotonic saline was administered to the rats. Group 2 was the ALA group (ALA; n = 6) in which rats received 100 mg/kg ALA. Groups 3 was the CMS (CMS; n = 7) in which 450.000 IU/kg/day of CMS was administered to the rats. Groups 4 was the CMS + ALA group (n = 6), in which rats were injected with 100 mg/kg of ALA 30 min before administration of CMS. All injections were performed intraperitoneally at 1, 4, 7, and 10 days. Urine was collected by using a metabolic cage for 24 h after each administration. The rats were euthanized under ether anesthesia after 24 h of the last administration. Blood and kidney samples then were collected for histological and biochemical analysis. ALA pretreatment could reverse the effects of colistin-induced nephrotoxicity, partly through its suppressing effect on Nox4 and caspase-3, which in turn results in its antioxidant and antiapoptotic effect. Therefore, ALA may be an effective strategy for the management of colistin nephrotoxicity.


2011 ◽  
Vol 31 (6) ◽  
pp. 565-573 ◽  
Author(s):  
M Tutanc ◽  
V Arica ◽  
N Yılmaz ◽  
A Nacar ◽  
I Zararsiz ◽  
...  

Aim: In cyclosporin-A (CsA)-induced toxicity, oxidative stress has been implicated as a potential responsible mechanism. Therefore, we aimed to investigate the protective role of erdosteine against CsA-induced nephrotoxicity in terms of tissue oxidant/antioxidant parameters and light microscopy in rats. Materials and methods: Wistar albino rats were randomly separated into four groups. Group 1 rats treated with sodium chloride served as the control, group 2 rats were treated with CsA, group 3 with CsA plus erdosteine, and group 4 with erdosteine alone. Animals were killed and blood samples were analyzed for blood urea nitrogen (BUN), serum creatinine (Cr), uric acid (UA), total protein (TP), and albumin (ALB) levels. Kidney sections were analyzed for malondialdehyde (MDA) and nitric oxide (NO) levels and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities, as well as for histopathological changes. Results: In the CsA group, MDA, GSH-Px, BUN, and Cr levels were increased. The TP and ALB levels were decreased. These changes had been improved by erdosteine administration. Other biochemical parameters did not show any significant change. Conclusion: These results indicate that erdosteine produces a protective mechanism against CsA-induced nephrotoxicity and suggest a role of oxidative stress in pathogenesis.


Author(s):  
Jonathan Esima ◽  
Abraham Zorte ◽  
O. Onwuli, Donatus ◽  
Waribo, Helen Anthony

Aim: Ibuprofen is analgesic, antipyretic and anti-inflammatory drug, which is widely used as a cheap over- the counter drug (OTC); however, this drug accompanies anti coagulation/anti platelets effects which sometimes might illicit adverse effects. In this study, we investigated effect of ibuprofen on prothrombin time (PT), activated partial thromboplastin time (aPTT) and platelet count using wistar albino rats. Methods: A total of 21 rats grouped into 3(control, acute and chronic exposure groups, with all consisting of 7 rats each) was used. The acute and chronic exposure group were given 0.7 mg of ibuprofen orally for 1 and 21 days, respectively. Blood sample was collected via cardiac puncture then analyzed. Results: PT was significantly higher in both group 2 and 3 (acute and chronic exposure, respectively) than that of the control. Acute exposure group showed the highest PT rise. A PTT was not significantly different between group 2 and 3 versus the control group. Platelet count was significantly lower in both group 2 and 3than that in the control group (p<0.05). Group 3 (chronic exposure) showed the lowest platelet count. Conclusion: Oral administration of ibuprofen affected coagulation parameters and a longer exposure reduce platelets count. A strictly prescription for this drug may be needed to prevent its indiscriminate use.


2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Vassilios Liakopoulos ◽  
Stefanos Roumeliotis ◽  
Xenia Gorny ◽  
Theodoros Eleftheriadis ◽  
Peter R. Mertens

Peritoneal dialysis (PD) patients manifest excessive oxidative stress (OS) compared to the general population and predialysis chronic kidney disease patients, mainly due to the composition of the PD solution (high-glucose content, low pH, elevated osmolality, increased lactate concentration and glucose degradation products). However, PD could be considered a more biocompatible form of dialysis compared to hemodialysis (HD), since several studies showed that the latter results in an excess accumulation of oxidative products and loss of antioxidants. OS in PD is tightly linked with chronic inflammation, atherogenesis, peritoneal fibrosis, and loss of residual renal function. Although exogenous supplementation of antioxidants, such as vitamins E and C, N-acetylcysteine, and carotenoids, in some cases showed potential beneficial effects in PD patients, relevant recommendations have not been yet adopted in everyday clinical practice.


2008 ◽  
Vol 28 (5_suppl) ◽  
pp. 38-42 ◽  
Author(s):  
Devrim Bozkurt ◽  
Pinar Cetin ◽  
Savas Sipahi ◽  
Ender Hur ◽  
Hasim Nar ◽  
...  

Background Encapsulating peritoneal sclerosis (EPS) is a clinical syndrome associated with symptoms of ileus and irreversible sclerosis of both visceral and parietal peritoneum. Peritoneal dialysis (PD) patients rarely develop EPS, a severe life-threatening condition of unknown pathogenesis. Angiotensin II is known to promote fibrosis and inflammation in various tissues. Renin–angiotensin system (RAS) blockade provides advantages in the course of diseases such as hypertension, chronic kidney disease, and proteinuria. We have also previously shown that RAS blockade has beneficial effects on hypertonic (3.86%) PD solution-induced peritoneal alterations. Because it shares the same characteristics as other fibrotic processes, peritoneal fibrosis can benefit from RAS blockade. Objective To determine the advantages of RAS blockade in regression of EPS. Methods We divided 56 nonuremic albino Wistar rats into 6 groups: control group ( n = 10), daily intraperitoneal (IP) injection of 2 mL isotonic saline for 3 weeks; CG group ( n = 10), daily IP injection of 2 mL/200 g chlorhexidine gluconate (CG) for 3 weeks; resting group ( n = 10), daily IP injection of CG (0 – 3 weeks) plus peritoneal rest (4 – 6 weeks). After 3 weeks of being injected with CG (0 – 3 weeks), a fourth group ( n = 9) was treated with 100 mg/L enalapril (ENA group); a fifth group ( n = 10) was treated with 80 mg/L valsartan (VAL group), and a sixth group ( n = 7) was treated with 100 mg/L enalapril + 80 mg/L valsartan (ENA+VAL group) in drinking water for an additional 3 weeks (4 – 6 weeks). At the end, a 1-hour peritoneal equilibration test was performed with 25 mL 3.86% PD solution. Dialysate-to-plasma ratio of urea (D/P urea), dialysate WBC count, ultrafiltration volume (UF), and morphological changes of parietal peritoneum were examined. Results Exposure to CG for 3 weeks resulted in alterations in peritoneal transport (increased D/P urea, decreased UF volume; p < 0.05) and morphology (increased inflammation, neovascularization, fibrosis, and peritoneal thickness; p < 0.05). Peritoneal rest had some beneficial effect only on UF failure and dialysate cell count ( p < 0.05). However, RAS blockade was more effective than peritoneal rest with respect to UF volume, vascularity ( p < 0.05), and peritoneal thickness ( p > 0.05). Dual blockade of RAS had no additional beneficial effects. Conclusion We suggest that RAS blockade either with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers may be a more effective option than resting in the management of EPS.


Author(s):  
A.Timucin ATAYOGLU ◽  
Sibel SILICI

Background: Infection can lead to delayed wound healing. Recently it has been shown that propolis which is used in complementary medicine has an antibacterial and anti-inflammatory effect. The aim of this study is to determine whether propolis may contribute to wound healing. Material and Methods: Twenty-one male Wistar albino rats were randomly divided into three groups. Group1 and Group 2 were topically treated with propolis ointment and Thiocillin® oinment, respectively while Group 3 was the control group. On incision wound model, Thiocillin® and propolis ointments were applied on wound sites once daily for 30 days and the mean epidermal thickness (MET) at the 30th day was compared while antimicrobial activity of propolis was studied against different pathogens as well. Results: Propolis exhibited in vitro antibacterial activity against Staphylococcus aureus, Escherichia coli, Streptococcus sp. and Pseudomonas sp. It is observed that the MET in the groups of Propolis ointment and Thiocillin® ointment were significantly greater than that of the control group, while the MET in the group of propolis ointment was significantly greater than that of Thiocillin® ointment treated group. Conclusion: Propolis is effective in wound healing. Further study in-depth is necessary to probe into clinical correlation.


2021 ◽  
Vol 11 (22) ◽  
pp. 10900
Author(s):  
Abdulsamet Emet ◽  
Erdi Ozdemir ◽  
Duygu Uckan Cetinkaya ◽  
Emine Kilic ◽  
Ramin Hashemihesar ◽  
...  

The high costs and extensive time needed for the treatment of critical-sized bone defects are still major clinical concerns in orthopedic surgery; therefore, researchers continue to look for more cost and time-effective methods. This study aims to investigate the effects of a decellularized omentum scaffold with a combination of platelet-rich plasma (PRP) and mesenchymal stem cells on the healing of critical-sized bone defects. Wistar albino rats (n = 30) were investigated in five groups. Critical-sized bone defects were formed on bilateral radius shafts. No scaffold, decellularized omentum, omentum with PRP and omentum + mesenchymal stem cells was used in group 1 (control group), 2, 3 and 4, respectively. In addition, omentum with a combination of mesenchymal stem cells +PRP was used in group 5. After 6 weeks, both radiological and histological healing were evaluated comparatively among the groups. After the use of a decellularized omentum scaffold, vitality of new cells was maintained, and new bone formation occurred. When compared to the control group, radiological healing was significantly better (p = 0.047) in the omentum and omentum + PRP-treated groups. Furthermore, histological healing was better in the omentum and omentum + PRP-treated groups than the control group (p = 0.001). The use of a decellularized omentum scaffold is suitable in the healing of critical bone defects.


Author(s):  
Eman I. Hassanen ◽  
Ahmed M. Hussien ◽  
Sally Mehanna ◽  
Marwa A. Ibrahim ◽  
Neven H. Hassan

Abstract Pesticides are viewed as a major wellspring of ecological contamination and causing serious risky consequences for people and animals. Imidacloprid (IM) and hexaflumuron (HFM) are extensively utilized insect poisons for crop assurance on the planet. A few investigations examined IM harmfulness in rodents, but its exact mechanism hasn’t been mentioned previously as well as the toxicity of HFM doesn’t elucidate yet. For this reason, the present study was designed to explore the mechanism of each IM and HFM–evoked rat liver and kidney toxicity and to understand its molecular mechanism. 21 male Wistar albino rats were divided into 3 groups, as follows: group (1), normal saline; group (2), IM; and group (3), HFM. Both insecticides were orally administered every day for 28 days at a dose equal to 1/10 LD50 from the active ingredient. After 28 days postdosing, rats were anesthetized to collect blood samples then euthanized to collect liver and kidney tissue specimens. The results showed marked changes in walking, body tension, alertness, and head movement with a significant reduction in rats’ body weight in both IM and HFM receiving groups. Significant increases in MDA levels and decrease of GHS levels were recorded in liver and kidney homogenates of either IM or HFM groups. Liver and kidney tissues obtained from both pesticide receiving groups showed extensive histopathological alterations with a significant increase in the serum levels of ALT, AST, urea, and creatinine and a decrease in total proteins, albumin, and globulin levels. In addition, there was upregulation of the transcript levels of casp-3, JNK, and HO-1 genes with strong immunopositivity of casp-3, TNF-ὰ, and NF-KB protein expressions in the liver and kidneys of rats receiving either IM or HFM compared with the control group. In all studied parameters, HFM caused hepatorenal toxicity more than those induced by IM. We can conclude that each IM and HFM provoked liver and kidneys damage through overproduction of ROS, activation of NF-KB signaling pathways and mitochondrial/JNK-dependent apoptosis pathway.


2001 ◽  
Vol 21 (2) ◽  
pp. 219-225 ◽  
Author(s):  
Soner Duman ◽  
Ali Ihsan Günal ◽  
Sait Sen ◽  
Gülay Asçi ◽  
Mehmet Özkahya ◽  
...  

Objective Peritoneal fibrosis (PF) is one of the most serious causes of failure in continuous ambulatory peritoneal dialysis (PD). Although the underlying mechanism responsible for the genesis of PF is still unknown, transforming growth factor p (TGFβ1) has been shown to be associated with PF. Angiotensin converting enzyme inhibitors have been shown to prevent the stimulating effect of growth factors. The aim of the present study was to investigate the effect of enalapril on peritoneal function and morphology in a rat model of experimental PF. Methods Twenty-one albino Wistar rats were divided into three groups: ( 1 ) the control group (C) received 10 mL isotonic saline intraperitoneally (IP), ( 2 ) the dextrose (Dx) group 10 mL 3.86% dextrose PD solution IP, and ( 3 ) the enalapril-treated group (ENA) 10 cc 3.86% dextrose PD solution IP plus 100 mg/L enalapril in drinking water. After 4 weeks, a 1-hour peritoneal equilibration test was performed with 20 mL 2.27% dextrose PD solution. Dialysate-to-plasma urea ratio (D/P urea), glucose reabsorption (D1/D0 glucose), ultrafiltration (UF) volume, and levels of dialysate protein, TGFβ1, and cancer antigen 125 (CA125) were determined. The parietal peritoneum was evaluated histologically by light microscopy. Results Administration of enalapril resulted in preserved UF (-0.2 ± 0.7 mL vs 1.7 ± 0.3 mL, p < 0.05), protein loss (2.3 ± 0.5 g/L vs 1.6 ± 0.2 g/L, p > 0.05), and peritoneal thickness (77 ± 7 μ vs 38 ± 5 μ, p < 0.001). D/P urea increased significantly in the Dx group ( p < 0.05). Both higher levels of TGFβ1 (undetectable vs 298 ± 43 pg/mL, p < 0.001) and lower levels of CA125 in dialysate effluent (0.94 ± 0.5 U/L vs 0.11 ± 0.1 U/L, p > 0.05) were determined in the Dx group. Conclusion These findings show that peritoneal morphology and function tests were dramatically deranged in the Dx group. The same properties were partially preserved in the ENA group. The production of TGFβ1 was significantly reduced but peritoneal thickness was not completely inhibited. In conclusion, by inhibiting the production of TGFβ1, enalapril can preserve peritoneal histology, peritoneal function, and remodeling of mesothelial cells.


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