Atorvastatin Improves Peritoneal Sclerosis Induced by Hypertonic PD Solution in Rats

2005 ◽  
Vol 28 (2) ◽  
pp. 170-176 ◽  
Author(s):  
S. Duman ◽  
S. ŞEn ◽  
E.Y. SÖZmen ◽  
D.G. Oreopoulos

Background Peritoneal sclerosis is a complication of peritoneal dialysis and results in ultrafiltration failure. It is related to chronic peritoneal injury due to dialysis solution content and recurrent peritonitis. Statins have anti-inflammatory properties which may be of value in modulating responses to injury. We evaluated the capacity of atorvastatin to modify peritoneal alterations secondary to hypertonic glucose. Methods Thirty-two non-uremic rats were divided into three groups: group I (Sham) rats received no treatment (n=11), group II received hypertonic (3.86%, 10 ml/day) PD solution (n=10) and group III received hypertonic PD solution (10 ml/day) plus 80 mg/L atorvastatin in drinking water (n=11). After four weeks, a one-hour peritoneal equilibration test (PET) was performed with 3.86% PD solution. Dialysate-to-plasma urea ratio (D/P urea), glucose reabsorption (D1/D0 glucose), ultrafiltration volume (UF), dialysate protein, TGF-ß1 and VEGF levels were determined. Results Administration of atorvastatin resulted in preserved UF (4.9±0.8 vs 7.5±0.6 mL, p <0.01), protein loss (2.2±0.2 vs 2.1±0.1 g/L, p >0.05), and peritoneal thickness (53±3 vs 26±4 μm, p <0.01). D1/D0 glucose was significantly reduced in the dextrose group (0.70±0.02 vs 0.56±0.04, p <0.01). Both higher levels of TGF-ß1 (206±40 vs 474±120 pg/mL, p<0.05), and VEGF in dialysate effluent (4±0.4 vs 7.9±3 pg/mL, p>0.05), was determined in the dextrose group. Conclusion Exposure to hypertonic glucose solution resulted in alterations in peritoneal transport manifested by a rapid dissipation of the glucose gradient and resultant impaired UF response. Administration of atorvastatin led to prevention of these alterations. We suggest that the anti-inflammatory properties of statins are useful in providing protection of the peritoneal membrane from the effects of hypertonic glucose.

2005 ◽  
Vol 28 (2) ◽  
pp. 156-163 ◽  
Author(s):  
S. Duman ◽  
S. ŞEn ◽  
C. Duman ◽  
D.G. Oreopoulos

Background Peritoneal sclerosis (PS) is one of the most serious causes of failure in long-term peritoneal dialysis. Angiotensin II is known to promote fibrosis and inflammation in various tissues. We previously showed that ACE inhibitors (ACEIs) have beneficial effects on hypertonic PD solutions (3.86% PD) induced peritoneal alterations. The aim of this study is to compare the effects of an ACEI and a receptor blocker on peritoneal alterations induced by hypertonic PD solutions in rats. Methods Forty-three non-uremic rats were divided into four groups: group I (Sham) rats received no treatment (n=11), group II received hypertonic (3.86%, 10 ml/day) PD solution (n=10) and groups III and IV received hypertonic PD solution (10 ml/day) plus 640 mg/L valsartan (n=11) and 100 mg/L lisinopril in drinking water (n=11). After four weeks, a one-hour peritoneal equilibration test (PET) was performed with 3.86% PD solution. Dialysate-to-plasma urea ratio (D/P urea), glucose reabsorption (D1/D0 glucose), ultrafiltration volume (UF), dialysate protein, TGFß1 and VEGF levels were determined. Results Administration of valsartan or lisinopril resulted in preserved UF (8±0.8 and 6.7±0.7 vs 4.9±0.8 mL), D1/D0 glucose (0.69±0.05 and 0.62±0.05 vs 0.56±0.04) and peritoneal thickness (19.4±2.9 and 28.5±5.2 vs 53±3 μm), respectively. Both higher level of TGF ß1 (206±40 vs 474±120 pg/mL, p<0.05), and VEGF in dialysate effluent (4±0.4 vs 7.9±3 pg/mL, p>0.05), was determined in the dextrose group. Both cytokines are partially inhibited by valsartan or lisinopril (p >0.05) Conclusion Exposure to hypertonic glucose solution resulted in alterations in peritoneal transport manifested by a rapid dissipation of the glucose gradient and resultant impaired UF response. Administration of valsartan or lisinopril led to attenuation of these alterations. We suggest that the equal protection of the peritoneal membrane from the effects of hypertonic glucose was achieved by receptor blockers and ACE inhibitors.


1975 ◽  
Vol 12 (2) ◽  
pp. 125-144 ◽  
Author(s):  
B. P. Stuart ◽  
R. D. Phemister ◽  
R. W. Thomassen

Spontaneous proteinuria in otherwise clinically normal adult Beagles 4–6 years old was studied for 2 years. Eighteen dogs, representing a population of 218 Beagles, were placed into three groups: group I, nonproteinuric; group II, intermittently proteinuric; group III, persistently proteinuric. The groups were alike on the basis of laboratory tests, except urinary protein loss. Proteinuria was persistent in most affected dogs but not progressive during the 2 years. The loss of proteins with high molecular weight, including α-, β-, and γ-globulins, suggested the proteinuria was of glomerular origin. There were glomerular lesions but no other significant change in the kidneys and urogenital system. Lesions were generalized and characterized by prominent, local or diffuse mesangial proliferation and by thickening, wrinkling, and splitting of the glomerular basement membrane. The subendothelial space was often widened and contained electron-dense deposits. Similar electron-dense deposits, as well as lipid and mineral, were in the mesangium. Alterations in visceral epithelial cells and endothelium were prominent. Periglomerular sclerosis was present but tended not to correlate with the severity of mesangial change in any given renal corpuscle. The severity of both mesangial and periglomerular changes increased with increasing proteinuria. Immunofluorescence studies demonstrated granular discontinuous localization of IgG and βIC-globulins in the glomerular capillaries and mesangium. Similar localization was seen but to a lesser extent in nonproteinuric dogs. The glomerular lesions seen in these clinically healthy, proteinuric dogs are similar to those described in various canine diseases associated with terminal renal failure.


2018 ◽  
Vol 6 (3) ◽  
pp. 1-4
Author(s):  
Haris Munandarnst ◽  
Marline N

Traditionally, (Tarenna polycarpa (Miq.) Koord Ex Valeton as known as marbosi-bosi which commonly found in Sibolga, North Sumatera, Indonesia has been used as antidiabetes, cholesterol, anti-inflammatory and antibacterial. Tarenna species has been found its activities as antimicrobial, anti-oxidant and anti-inflammatory activity. The aim of this study was to investigate the anti inflammatory effect ethanol extract of marbosi-bosi leaves (Tarenna polycarpa (Miq.) Koord Ex Valeton in terms of decreased edema volume of male white rat in 1% carrageenan-induced and also to determine the effective dose of extract to decrease the volume of rat paw edema Ethanol extract of marbosi-bosi (Tarenna polycarpa (Miq.) Koord Ex Valeton was obtained by maceration. The antiinflammatory activity test was divided into 5 groups. The Group I (negative control) was given CMC 0.5%, Group II (positive control) was given diclofenac sodium 2,25 mg / kg BW, while Group III, IV and V were  given marbosi-bosi leaf extract at a dose of 50, 100 and 200 mg/kgBW respectively.  Each rat was induced by 1% carrageenan subplantar injection. Examination of antiinflammatory effect was measured by using digital plethysmometer at minute of 30 to minute of 360. The data were analyzed statistically using ANOVA (analysis of variance).The results showed that negative control did not show anti-inflammatory effect had significant differences with other treatment groups. In conclusion, ethanol extract marbosi-bosi (Tarenna polycarpa (Miq.) Koord Ex Valeton has an effective anti-inflammatory activity at a dose of 100 mg / kgBW.


2013 ◽  
Vol 5 (1) ◽  
Author(s):  
Poppy M Lintong ◽  
Lily L. Loho ◽  
Herman Anggran

Abstract: Aspirin is one of the non-steroid-anti-inflammatory drugs. Its pharmacodynamic effects are as an analgesic, antipyretic, anti-inflammatory, anti-thrombotic, and uricosuric agent. The side effects of aspirin are on the respiratory tract, the gastrointestinal tract, blood, metabolic processes, endocrine functions, pregnancy, hypersensitivity, and drug interaction. The purpose of this study was to evaluate the macroscopic and microscopic features of wistar rat stomachs after the administration of aspirin. This was an experimental study, using nine wistar rats divided into three groups equally. Group I, the control group, was given a food pellet only. Group II was given the pellet, added with aspirin 21 mg daily for 10 days. Group I and Group II were terminated on day 11. Group III was given the pellet, added with aspirin 21 mg/day for 10 days, and was terminated on day 14. All the wistar rat stomachs were examined macroscopically and microscopically. The results showed that the control group had a macroscopically normal stomach architecture, and the mucosa layers and rugae were intact and looked pinkish white. The groups treated with aspirin still showed normal stomach architecture, and the mucosa layers and rugae were intact but looked more palid than that of the control group. Microscopically, the stomach walls of the control group were normal, but groups treated with aspirin for 10 days revealed edema of the lamina propria, dilatation of capillaries; and predominantly neutrophilic infiltration in the lamina propria. Ceasing of aspirin administration showed a resolution of the inflammatory process, marked by diminished infiltration of PMN cells and tisuue edema. Conclusion: Aspirin treatment of 21 mg a day for 10 days revealed histopathologically acute gastritis of the wistar rat stomach walls. The inflammatory reaction was diminished after the cessation of aspirin. Keywords: aspirin, histopathology, stomach.   Abstrak: Aspirin tergolong obat anti-inflamasi non-steroid (AINS) yang secara farmakodinamika mempunyai efek analgesik, anti-piretik, anti-inflamasi, anti-trombotik, dan urikosurik, namun mempunyai efek samping pada saluran  cerna terutama lambung. Penelitian ini bertujuan untuk mendapatkan gambaran histopatologik (makroskopik dan mikroskopik) lambung tikus Wistar setelah pemberian aspirin. Penelitian ini bersifat eksperimental dengan menggunakan sampel sembilan ekor tikus Wistar yang dibagi atas tiga kelompok. Kelompok I (kontrol) terdiri dari tiga ekor tikus yang diberi pelet biasa dan air minum. Kelompok II terdiri dari tiga ekor tikus yang diberi pelet biasa, air minum, dan aspirin dosis 21 mg/hari  selama 10 hari. Pada hari ke-11 kelompok I dan II diterminasi. Kelompok III terdiri dari tiga ekor tikus yang diberikan pelet biasa, air minum, dan aspirin dosis 21 mg/hari selama 10 hari, kemudian aspirin dihentikan dan tikus diterminasi pada hari ke-14. Setelah diterminasi, kelompok I-III diotopsi, diambil organ lambungnya, kemudian dilakukan pemeriksaan histopatologik. Hasil penelitian memperlihatkan makroskopik mukosa lambung tampak lebih pucat sedangkan mikroskopik menunjukkan tanda-tanda radang akut. Penghentian pemberian aspirin diikuti dengan resolusi reaksi inflamasi yang ditandai oleh penurunan infiltrasi sel-sel radang PMN dan edema jaringan. Sinpulan: Pemberian aspirin 21 mg/hari selama 10 hari mengakibatkan terjadinya gambaran histopatologik gastritis akut pada lambung tikus Wistar. Reaksi inflamasi menurun setelah penghentian pemberian aspirin. Kata kunci: aspirin, histopatologi, lambung.


2020 ◽  
Vol 104 (5) ◽  
pp. 36-43
Author(s):  
P. Leonenko ◽  
◽  
Yu. Kokoieva ◽  

Summary. Inflammation and pain can lead not only to a deterioration in the patient’s condition, but also to such local consequences as: bone resorption, loss of soft tissue volume, an increase in the wound healing time and patient rehabilitation in general. Inflammation-induced bone resorption in the area of implantation with direct prosthetics, caused by the activity of cytokines and prostaglandins, negatively affects the entire result of treatment of dentition defects in general. This is because the quality and quantity of bone tissue is one of the key points in the success of prosthetics on dental implants, therefore, pharmacological support of dental implantation and direct prosthetics is an important component of treatment. Purpose: to investigate the effect of inflammation and pain on peri-implant bone tissue at the stages of dental implantation and direct prosthetics and scientifically substantiate pharmacological support in order to prevent inflammatory bone resorption. Materials and methods. A clinical prospective study of 57 patients was carried out at the stage of dental implantation and direct prosthetics with randomization according to the type of pharmacological accompaniment: 1) group I received anti-inflammatory therapy in the form of a balanced inhibitor of COX-1, COX-2 and 5-LOG – nimesulide and analgesic therapy – dexketaprofen trometamol; 2) group II received anti-inflammatory therapy – a selective COX-2 inhibitor – meloxicam and analgesic therapy – ibuprofen; 3) group III did not receive anti-inflammatory and analgesic therapy due to contraindications to the use of non-steroidal anti-inflammatory drugs. Patients of groups I, II, III underwent: clinical, radiological and functional research methods by monitoring the state in dynamics. Results. According to the data obtained, the indices of pain intensity in group I were significantly lower (p < 0.05) as of 1 and 2-d days, compared with groups II and III. The stabilization of inflammatory processes in group I was recorded on the 2-d day. There was a significant decrease (p < 0.05) in the signs of the inflammatory process in patients of group I on the 3rd day (3.01±0.11 units), and on the 7-th day – their complete absence (1.12±0.23 units). In group II, significant regression of inflammation was noted on the 4th day (3.14±0.12 units), and on the 7-th day, minimal signs were observed (2.04±0.17 units). A decrease in signs of inflammation in group III occurred from the 5th day (3.31±0.28 units), and inflammatory phenomena were observed on the 7th day of the study (2.65±0.27 units). In group I, there was a significant stop in the loss of stability of the connection between the bone tissue and the dental implant on the 20-th day (65.08±1.03 points). As of the 25-th day, in patients of group I of the study, there was significantly higher (p < 0.05) indicators of the coefficient of stability of the implant (66.21±1.40 points) in relation to group II of patients (62.93±0.94 points), in who used selective COX-2 inhibitors, and group III (62.90±0.75 points), where NSAID’s were not used. The loss of marginal bone around the dental implant during the study period in group I was 0.5±0.23 mm CI, in group II – 1.1±0.34 mm, in group III – 1.3±0.28 mm. Side effects in group I of the study were recorded in 5.3 % of patients taking drugs nimesulide and dexketoprofen, and in 15.8 % of those in group II who took drugs meloxicam and ibuprofen. Conclusions. Complex pharmacological support of dental implantation and direct prosthetics on implants in the treatment of dentition defects, consisting of perioperative analgesia – dexketoprofen trometamol, as well as nimesulide for anti-inflammatory therapy, made it possible to influence the trauma-induced bone resorption in the implantation area by controlling inflammation. As a result, on the 20-th day in the patients of the group I of the study, a significant stop was noted in the loss of stability of the connection of the bone tissue and the dental implant (65.08±1.03 units), and on the 25-th day of the study in the group I it was found significantly higher (p < 0.05) indicators of the coefficient of stability of the implant and less loss of height of marginal bone tissue in relation to groups II and III of patients. This pharmacological complex made it possible to achieve stabilization of pathological processes in soft tissues – stopping the formation of edema on the 2-d day, a significant decrease (p < 0.05) of signs of the inflammatory process on the 3-d day (3.01±0.11 points) and to implement effective pain prevention at the stages of dental implantation and direct prosthetics.


2021 ◽  
Vol 12 (3) ◽  
pp. 2813-2825

The present study was carried out to study coumestan derivative wedelolactone in Indomethacin-induced enterocolitis in rats. Wistar rats were randomly divided into three groups containing six animals per group. Group I served as normal control. Group II, Group III & Group IV receive 7.5 mg/kg, s.c, indomethacin on two consecutive days. Group III and Group IV have received a wedelolactone dose of 50 mg/kg, and 100 mg/kg per oral, respectively, for 14 days after the induction with indomethacin. The protective effect was measured based on intestinal parameters of the disease activity index, colitis score, myeloperoxidase (MPO) activity in the colon. The inflammation biomarkers were quantified by ELISA in the rat colon. Further, activity was ascertained by histopathology. Pro-inflammatory functions IL-1a, IL-1b, IL-2, TNF, INFγ, STAT3, and CCL-5 play an important role in the variation of the intestinal immune system. Wedelolactone showed significantly decreased Disease activity index, Colitis score, Myeoloperoxidase activity. Expression of pro-inflammatory was increased in indomethacin-induced groups and was significantly suppressed in animals administered with wedelolactone at 50 mg/kg & 100 mg/kg dose (p<0.01 & p<0.001). Histological reports also revealed that treated groups have comparatively less damage than that of the induced groups. We concluded that wedelolactone showed an anti-inflammatory effect by downregulation of the IL-6/STAT3 inflammatory signaling pathway and the equilibrium production of pro-inflammatory cytokines.


Introduction. Nonsteroidal anti-inflammatory drugs are the most commonly used medicines in medical practice. As literary sources show, they often cause unwanted side-effects. The purpose of our work was to evaluate the frequency, clinical manifestations and morphological features of lesions of the gastroduodenal zone that arise in patients of rheumatologic, neurological profiles and angiosurgery department during the course of treatment with nonsteroidal anti-inflammatory drugs of different groups, to trace the dependence of the frequency of manifestations of the pathology of the stomach and duodenum from simultaneous receiving two nonsteroidal anti-inflammatory drugs and their combination with glucocorticosteroids and anticoagulants. Material and methods. 73 patients who had used NSAIDs for a long time and had endoscopically confirmed medicated gastroduodenopathy. Patients were divided into 3 groups depending on the profile of the department: Group I included - 24 patients of the department of vascular surgery; Group II - 23 patients of the neurological department; Group III - 26 patients with rheumatological profile. Results. Asymptomatic clinical picture of NSAID-gastropathy was found, which did not coincide with the available endoscopic changes in the gastroduodenal tube: in 63% of cases, erosive changes in the mucous membrane were present, and stomach and duodenal ulcers were revealed in 11%. It was also found that in the group of patients receiving proton pump inhibitors, the incidence of gastroduodenopathy was reliably lower (34.2%) than in patients who did not receive them (53.4%). During this study, it was found that the use of selective non-steroidal anti-inflammatory drugs can significantly reduce the probability of developing the pathology of the gastroduodenal zone, compared with non-selective. Conclusions. The course of treatment with nonsteroidal anti-inflammatory drugs should be as short as possible and should be carried out with minimal but effective doses. Parallel prophylactic administration of proton pump inhibitors is appropriate in patients at high risk of developing erosions and ulcers in the background of treatment with these drugs.


Author(s):  
Paulina Maya Octasari ◽  
Fransiska Ayuningtyas

Cream<span style="text-decoration: line-through;">s </span>and ointment<span style="text-decoration: line-through;">s</span> are topical dosage forms used in the manufacture of drugs. Topical anti-inflammatory drug is a solution to problems of gastrointestinal side effects caused by taking nonsteroidal anti-inflammatory drug orally. The compound 2,5-bis (4-nitrobenzilidine) cyclopentanone is an analog of curcumin which has better anti-inflammatory activity than curcumin. This study aimed to determine the antiinflammatory effect of cream and ointment from 2,5-bis (4-nitrobenzilidine) cyclopentanoneagainst edema in mice induced by formalin. This research were experimental randomized complete design using a single factor. Twenty mice were divided into 4 groups: group I were given a cream base, the group II were given ointment base, group III were given cream compound 0.25% and group IV were given ointment compound 0.25%. The data were processed into AUC values and the percentage of anti-inflammatory effectwere calculated. Results were analyzed using ANOVA and T-test statistics. The results showed that between the dosage form had statistically difference of anti-inflammatory effect (p&lt;0.05). The ointmentshowed a greater value of antiinflammatory activity rather than cream.


2001 ◽  
Vol 21 (3_suppl) ◽  
pp. 349-353 ◽  
Author(s):  
Hidetomo Nakamoto ◽  
Hiroe Imai ◽  
Yuji Ishida ◽  
Yasuhiro Yamanouchi ◽  
Tsutomu Inoue ◽  
...  

Objective Encapsulating peritoneal sclerosis (EPS), in which all or part of the intestine is enveloped in a fibrous ball resembling a cocoon, is a serious complication of peritoneal dialysis (PD). The aim of the present study was to investigate whether pH-neutral or acidic dialysis solutions induce peritoneal fibrosis. Design We divided 18 male Wistar–Kyoto (WKY) rats into three groups and dialyzed them with various solutions as follows: group I, 10 mL acidic dialysis solution (pH 3.8, containing 1.35% glucose), n = 6; group II, 10 mL pH 5.0 dialysis solution, n = 6; and group III, 10 mL neutral dialysis solution (pH 7.0), n = 6. Peritoneal catheters were inserted, and dialysis solution was injected every day for 40 days. At the end of the experiment, a peritoneal equilibration test (PET) was performed. Expression of mRNA of aquaporins 1 and 4 (AQP-1 and AQP-4) in the peritoneum were studied by semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR). Results In rats treated with pH 3.8 dialysis solution, necropsy findings revealed features identical to those of EPS. The typical appearance was of granulation tissue or fibrotic tissue (or both) covering multiple surfaces. Multiple adhesions were present. In microscopic examinations, peritoneal fibrosis and loss of mesothelium were found. In rats treated with pH 7.0 dialysis solution, no signs of EPS were seen. In rats treated with pH 5.0 dialysis solution, milder changes (subserosal thickening and partial adhesion of the peritonea) were observed. The mRNA of AQP-1 and AQP-4 were expressed in the peritonea of the rats. The expression of the AQPs was significantly suppressed in rats treated with pH 3.8 dialysis solution. Conclusions In rats, long-term intraperitoneal injection of acidic dialysis solution produced features typical of EPS in humans. Newly developed neutral dialysis solutions protected the against the development of EPS during peritoneal dialysis in rats.


2020 ◽  
Vol 11 (4) ◽  
pp. 5539-5545
Author(s):  
Dwintha Lestari ◽  
Indrati ◽  
Anggun Rafisa

Inflammation is a body tissue reaction to the damage caused by foreign object. One of the plants that the community uses to eliminate inflammation is cashew leaf (Anacardium occidentale L). This research aimed to find out if the guava extract has an anti-inflammatory effects compared with diclofenac. This was an experimental study using 30-tails Wistar strain, which is divided into 6 groups that every 1 hour later induced lambda-carrageenan. Group I and IV are given ethanolic extract of cashew leaf 300 mg/kg BW. Group II and V were given cellulose (CMC) 1% as a control. Group III and VI were given diclofenac 4.5 mg/kg of BW. Edema volume from hour 1 to 6 and MDA levels of foot tissue in the hour 6 were measured in group I, II, III. Hyperalgesia was measured in group IV, V and VI. All research results were statistically tested with ANOVA test followed by the Newman Keuls test. Ethanolic extract of cashew leaf 300 mg/kg BW inhibited the formation of edema volume, preventing hyperalgesia significantly (P &lt; 0.05) compared to a group of control and diclofenac. Measurement of MDA levels between groups with ethanolic extract of cashew leaf, control, and diclofenac was not significantly different (P &gt; 0.05). Ethanolic extract of cashew leaf has an anti-inflammatory effect based on inhibition of edema volume, hyperalgesia.


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