Antiproliferative and anti-inflammatory properties of diindolylmethane and lupeol against N-butyl-N-(4-hydroxybutyl) nitrosamine induced bladder carcinogenesis in experimental rats

2015 ◽  
Vol 35 (6) ◽  
pp. 685-692 ◽  
Author(s):  
B Prabhu ◽  
D Balakrishnan ◽  
S Sundaresan

Introduction: Chemoprevention may involve perturbation of a variety of steps in tumor initiation, promotion, and progression. Objective: To investigate the antiproliferative and anti-inflammatory potential effects of diindolylmethane (DIM) and lupeol on experimental bladder carcinogenesis. Methods: Sixty healthy male Wistar rats were selected and randomly divided into six groups, with 10 rats in each group. Group I: control; group II: N-butyl- N-(4-hydroxybutyl) nitrosamine (BBN; 150 mg/gavage/twice a week) for 8 weeks, and then they were given 100 ppm concentrations of dimethylarsenic acid (DMA) in the drinking water for 28 weeks; group III: BBN + DMA + DIM (5 mg/kg body weight (b.w.)/day) treatment was started after BBN treatment, and it was orally administered for 28 weeks); group IV: BBN + DMA + lupeol (50 mg/kg b.w./day) treatment was started after BBN treatment, and it was orally administered for 28 weeks); and groups V and VI: DIM and lupeol treatment alone for 36 weeks. Bladder tissues were collected after 36th week study protocol for further analysis. Results: Our results revealed that DIM and lupeol treatment showed inhibition of tumor growth in the bladder by histopathological confirmations as well as significantly ( p < 0.001) increased the expression of phosphotensin (PTEN) and significantly ( p < 0.001) decreased the expression of tumor necrosis factor α, nuclear factor κβ (p65) were quantified using Western blot analysis. DIM and lupeol treatment significantly ( p < 0.001) decreased the levels of Cox-2 in bladder tissue samples and NMP 22 in urine samples were quantified using enzyme-linked immunosorbent assay method. Conclusion: Preventive DIM and lupeol administration act as potent Cox-2 inhibitors, which activates the tumor suppressor protein PTEN against experimental bladder carcinogenesis by antiproliferative and anti-inflammatory properties.

2020 ◽  
Vol 92 (6) ◽  
pp. 46-52
Author(s):  
Natalya V. Chebotareva ◽  
Anatoly A. Vinogradov ◽  
Alla A. Gindis ◽  
Irina N. Bobkova ◽  
Wenjing Cao ◽  
...  

Chronic glomerulonephritis (CGN) is a disease with a steadily progressing course, which is based on inflammation with the activation of immune cells. The severity of the inflammatory reaction in the kidney tissue is determined by the balance of locally pro-inflammatory factors and protective mechanisms, which include anti-inflammatory cytokines and T-regulatory lymphocytes (Treg). The study of processes that can modulate the severity of inflammation in the kidney is of particular interest for understanding the basic patterns of CGN progression. Aim. To determine the clinical significance of the Th17, Th1, and Treg cytokines in urine to assess the activity and progression of chronic glomerulonephritis with nephrotic syndrome (NS). Materials and methods. The study included 98 patients with CGN 37 women and 61 men. Patients were divided into two groups according to the degree of CGN activity. Group I consisted of 51 patients with NS. In 21 subjects, a decrease in GFR60 ml/min was revealed. Group II included 47 patients with proteinuria from 1 to 3 g/day without NS. GFR60 ml/min/1.73 m2 was observed in 26 patients. A kidney biopsy was performed in 65 patients and the hystological diagnosis was verified: 20 had mesangioproliferative GN, 16 had membranous nephropathy, 18 had focal segmental glomerulosclerosis, and 11 had membranoproliferative GN. The control group consisted of 15 healthy people. The levels of IL-6, IL-10, IL-17, tumor necrosis factor a (TNF-a) in the urine were determined using enzyme-linked immunosorbent assay. The number of FoxP3-positive cells in the inflammatory interstitial infiltrate of the cortical layer was determined in 39 patients (in a biopsy sample in a 1.5 mm2 area). Results. In group of patients with CGN, there was an increase in the levels of Th17, Th1, and Treg cytokines in urine TNF-a and IL-10 compared with healthy individuals. An increase in the levels of IL-6 in the urine of patients with high clinical activity of CGN (with NS and renal dysfunction) was more pronounced than in patients with NS and normal renal function. There was a decrease in the number of Treg cells in the interstitium of the kidney and a decrease in the production of anti-inflammatory IL-10 in CGN patients with NS, compared with patients without NS. The most pronounced changes in the cytokine profile were observed in patients with FSGS with an increase in pro-inflammatory cytokines and a decrease in Treg in the kidney tissue/anti-inflammatory IL-10 in the urine. Conclusion. An imbalance of cytokines characterized by an increased levels of pro-inflammatory IL-17, IL-6, TNF-a, and a reduced levels of anti-inflammatory IL-10 and T-regulatory cells in the kidney tissue is noted in patients with NS, especially with FSGS. Imbalance of cytokines reflects the high activity of CGN and the risk of the progression of the disease.


2016 ◽  
Vol 7 (4) ◽  
pp. 175-178
Author(s):  
Solmaz Pourzare Mehrbani ◽  
Zohreh Babaloo ◽  
Zahra Jamali ◽  
Tahmoores Abdollahian ◽  
Hosein Eslami ◽  
...  

ABSTRACT Background Air pollution in cities has always been a permanent and serious threat for the health of society and the environment, influencing the health of different body organs and systems both acutely and chronically. Therefore, the aim of this study is to investigate the effect of air pollution in saliva Interleukin-8 (IL-8) levels in children. Materials and methods A total of 88, 8- to 10-year-old children were included in this descriptive cross-sectional study. Group I, the case group, included 44 children from Tabriz (Iranian Azerbaijan), and group II, the control group, included 44 children from Kalibar Town (of Tabriz). Both groups in this study had a similar economic status. Following sampling and selection of individuals, for measuring the levels of saliva IL-8, ELISA (enzyme-linked immunosorbent assay) method was used. To investigate the difference between the means of the groups, independent t test or its nonparametric equivalent, i.e., Man—Whitney test and Statistical Package for the Social Sciences (SPSS) 21 were used. In this study, p-value lower than 0.05 was considered statistically significant. Results The results of this study indicate a significant difference in the levels of saliva IL-8 between the two groups, where the mean level of saliva IL-8 is greater in children residing in the region with higher air pollution level than in the children dwelling in the region with a greater air pollution level (p = 0.001). Conclusion The results obtained from this study indicated that the level of saliva IL-8 increases in regions with air pollution, potentially causing several mouth problems in children. How to cite this article Mehrbani SP, Babaloo Z, Jamali Z, Abdollahian T, Eslami H, Sobhani N. Effect of Air Pollution on Salivary Interleukin-8 Levels in Children. World J Dent 2016;7(4):175-178.


Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 191 ◽  
Author(s):  
Polina Vishnyakova ◽  
Anastasiya Poltavets ◽  
Maria Nikitina ◽  
Konstantin Midiber ◽  
Liudmila Mikhaleva ◽  
...  

Preeclampsia is a gestation-associated hypertensive syndrome that threatens the life and health of the mother and the child. The condition is presumably caused by systemic failure with a strong involvement of innate immunity. In particular, it has been associated with flexible phenotypes of macrophages, which depend on the molecules circulating in the blood and tissue fluid, such as cytokines and hormones. This study aimed at a comparative evaluation of pro-inflammatory (TNFα) and anti-inflammatory (CD206, MMP9, HGF) markers, as well as the levels of estrogen receptor α, expressed by decidual macrophages in normal pregnancy and in patients with early- and late-onset preeclampsia. The tissue samples of decidua basalis were examined by immunohistochemistry and Western blotting. Isolation of decidual macrophages and their characterization were performed using cultural methods, flow cytometry and real-time PCR. Over 50% of the isolated decidual macrophages were positive for the pan-macrophage marker CD68. In the early-onset preeclampsia group, the levels of estrogen receptor α in decidua were significantly decreased. Furthermore, significantly decreased levels of HGF and CD206 were observed in both preeclampsia groups compared with the control group. The observed downregulation of estrogen receptor α, HGF and CD206 may contribute to the balance of pro- and anti-inflammatory macrophages and thereby to pathogenesis of preeclampsia.


2020 ◽  
Vol 22 (5) ◽  
pp. 879-886
Author(s):  
R. F. Sholan

The purpose of this work was to study the relationships between urinary cytokines, mast cells and nerve growth factor (NGF) in the patients with interstitial cystitis/bladder pain syndrome (IC/BPS). Sixty-eight women with clinically diagnosed IC/BPS were under study. Their mean age was 54.2±12.4 years. Urinary concentrations of interleukins (IL-1β, IL-6, IL-8), tumor necrosis factor-α (TNFα), and NGF were determined by ELISA technique. Mast cells were identified in biopsies of mucous membranes from urinary bladder harvested during cystoscopy. Statistical evaluation was performed by Statistica program in Microsoft Excel. Pearson correlation quotients were calculated. Depending on the type of IC/BPS, the patients were divided into 2 groups: group I included 36 patients with classic type of disease; group II comprised 32 patients with non-ulcer type of IC/BPS. No significant differences were revealed between the groups. In 13.9% of patients from group I, the onset of clinical manifestations of the disease was observed at the age of less than 40 years; in group II, 28.1% of the examined mentioned appearance of the disease symptoms at this age. The levels of IL-1β in the patients from group I was 2.4 times higher than in controls (p < 0.05). IL-6, IL-8 and TNFα concentrations exceeded control values by 2.0 (p < 0.05), 2.5 (p < 0.05) and 2.0 times (p < 0.05), respectively. In the patients from group II, the content of IL-1β, IL-6, IL-8 and TNFα was 2.4 (p < 0.05), 2.0 (p < 0.05), 2.0 (p < 0.05) and 1.9 (p < 0.05) times higher than in the control group, respectively. There were no significant differences between groups I and II, in IL-1β, IL-6, and TNFα levels, except of IL-8 in women of group I that was 20.3% higher than in group II. The urinary NGF level in the patients with IC/BPS exceeded the control level 1.6 times (p < 0.05) for group I, and 1.5 times (p < 0.05) for group II. The number of mast cells in the patients of group I was significantly higher than in controls and in group II, i.e., 1.6 (p < 0.05) and 1.4 times (p < 0.05), respectively. In most cases, a direct weak correlation was revealed between the indices. Only in group I, a moderate correlation (r = + 0.508) could be detected between IL-1β and mast cells. Determination of cytokine levels allows to detect activation of inflammatory cells in bladder tissue and provides an opportunity for developing diagnostic strategies. Increased numbers of mast cells may indicate the importance of these cells in the disease progression, whereas elevated levels of NGF in urine suggests that IC/BPS may be caused by chronic inflammation.


2020 ◽  
Author(s):  
Jin-hu Chen ◽  
Jian-ting Zhao ◽  
Zheng-yong Yu ◽  
Yi-hao Che ◽  
Yu-jia Wang ◽  
...  

Abstract Background: Mucosal inflammation and ulcer play important roles in the pathogenesis of ulcerative colitis. As as traditional Chinese medicine compound composed of Periplaneta americana and Taraxacum mongolicum, Ento-PB is always prescribed for the treatment of ulcer and inflammatory diseases. As for the significant role of P. americana in terms of promoting mucosal healing, the compatibility of the anti-inflammatory drug T. mongolicum may enable Ento-PB to simultaneously play anti-inflammatory and promote mucosal healing effects on the treatment of UC. Therefore, this study aimed to evaluate the therapeutic potential and possible mechanism of Ento-PB for UC by establishing an acetic acid-induced colitis model in dogs.Methods: Preliminary identification to the chemical components of compound Ento-PB was carried out through high performance liquid chromatography. A cross-bred dogs model of acetic acid-induced ulcerative colitis was established to evaluate the efficacy of compound Ento-PB. The expression levels of inflammatory cytokines C-reactive protein (CRP), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-10 (IL-10) in plasma were measured by carrying out enzyme-linked immunosorbent assay (ELISA).Results: With the extension of treatment time, Ento-PB could effectively improve clinical symptoms of UC cross-bred dogs. Colonoscopy displayed that mucosal redness, swelling and congestion decreased gradually, and obviously repaired after mucosal injury. The intestinal texture was gradually clear, and the colonoscopy score gradually reduced. Histopathological examination revealed that the structure of colon was restored significantly, the infiltration of inflammatory cells was reduced, and the histological score was remarkably reduced. At the same time, the results of dynamic monitoring of inflammatory cytokines in plasma proved that Ento-PB can gradually down-regulate the activity of CRP, iNOS and COX-2, reduce the expression levels of inflammatory cytokines TNF-α and IL-1β, and gradually restore anti-inflammatory and the expression level of cytokine IL-10.Conclusions: Ento-PB reduces the level of pro-inflammatory cytokines in a dose- and time-dependent manner and inflammation, improves colon tissue lesions and the repair of intestinal mucosa after injury, and effectively increases acetic acid-induced colon inflammation in UC cross-bred dogs.


2021 ◽  
Vol 18 ◽  
Author(s):  
Jagseer Singh ◽  
Pooja A Chawla ◽  
Rohit Bhatia ◽  
Shamsher Singh

: The present work reports synthesis and screening of fifteen 2,5-disubstituted-4-thiazolidinones with different substitutions of varied arylidene groups at imino. The structures of the compounds were confirmed by spectral characterization. The compounds were subjected to in vivo anti-inflammatory and in vitro antioxidant activities. The derivatives possessed remarkable activities quite close to standard drugs used. Unlike conventional non-selective NSAIDs, the synthesized compounds did not contain any acidic group, thereby ensuring a complete cure from ulcers. To further substantiate the claim for safer derivatives, the active compounds were docked against the cyclooxygenase (COX)-2 enzyme. It was found that 4-fluorophenylimino substituent at 2- position and 3-nitro moiety on a 5-benzylidene nucleus of the 4-thiazolidinone derivative fitted in the COX-2 binding pocket. The compounds exhibited remarkable activity in scavenging free radicals, as depicted by the DPPH assay method. The structure-activity relationship was also established in the present work with respect to the nature and position of the substituents. The active compounds were evaluated for drug-like nature under Lipinski’s rule of five, and the toxicity behaviour of active compounds was predicted using ADMETlab software. The compounds have the potential to target degenerative disorders associated with inflammation and the generation of free radicals.


Author(s):  
GOMATHI KANNAYIRAM ◽  
SANDHYA A ◽  
SOWMIYA S ◽  
VALARMATHI S ◽  
DANIEL JOSEPH

Objective: The aim of this study is to evaluate the anti-inflammatory activity of Nigella sativa silver nanoparticles (NS AgNPs). Methods: Fourier transform infrared analysis was used to characterize the NS AgNPs and the extract. 2,2-diphenylpicrylhydrazyl assay was done to test the antioxidant potency of NS AgNP. Furthermore, in vitro anti-inflammatory activity of the extract and the NS AgNP was determined by red blood cell (RBC) membrane stabilization assay, protein inhibition assay, and interleukin-1 (IL-1) beta assay. Results: The NS AgNP exhibited dose-dependent antioxidant property. At the concentration 0.01 mg/ml 80% of radical was scavenged by NS AgNP. Inhibition of protein denaturation assay also suggests that NS AgNP shows the highest activity (70%) when compared with the standard drug aspirin (65%). RBC assay suggests that NS AgNP stabilizes the RBC membrane and prevents leaking. In the enzyme-linked immunosorbent assay method the NS AgNP showed better IL-1 beta inhibition activity when compared to aqueous extract. Conclusion: From the study, it was inferred that NS AgNPs are more effective when compared to the extract. These results suggest that NS AgNP can be used to treat inflammatory disorders.


QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
M E Nasser ◽  
S M Shawky ◽  
E A M Sanad

Abstract Background The biology of claudins is a rapidly evolving field, and many intriguing questions remain unanswered. Although it had been assumed that the reason there are ≥24 isoforms of claudin is that each one has distinct permeability properties. The nephron displays a wide spectrum of claudins, whose distribution varies in each tubular segment. In diabetic nephropathy and glomerulonephritis the gene expression of claudin-1, is markedly upregulated in the podocyte, accompanied by a tighter filtration slit diaphragm (cell-cell junction made by the glomerular podocytes) and the appearance of TJ-like structures between the foot processes causing further podocytes injury and proteinuria. Aim of the work to assess urinary claudin -1 level as a marker of podocyte injury in patients with proteinuria. Patients and Methods it is a case control study which was conducted upon 90 subjects who were divided into three groups: group I included 30 patients with type II DM, group II included 30 patients with glomerulonephritis and group III had 30 healthy subjects as controls. Urinary claudin-1 level was measured by Enzyme linked Immunosorbent Assay (ELISA) Results In this study, we found that urinary claudin-1 level was significantly higher in diabetics group and GN group than in control group. In comparison between GN group and diabetic group, we found that urinary claudin-1 level was higher in GN group than in diabetics group but with no statistically significant difference between the two groups. Conclusion urinary claudin-1 level was significantly higher in diabetics and GN group and has positive correlation with uACR. So it can be used as marker of podocytes injury and proteinuria


2017 ◽  
Vol 8 (1) ◽  
pp. 21-25
Author(s):  
Anita Rawat ◽  
Anil Kumar Gangwar ◽  
Archana Ghildiyal ◽  
Neena Srivastava ◽  
Sunita Tiwari ◽  
...  

Background: Pre-eclampsia(PE) is  the  most  frequently encountered  medical  complication  during  pregnancy. In developing countries PE   is a principal cause of maternal mortality. A disturbance  in  the  angiogenic/antiangiogenic  factors  and  in  the  hypoxia/placental re-oxygenation  process,  seems  to  activate a maternal  endothelial  dysfunction.Aims and Objective: To estimate Vascular Endothelial Growth Factor ( VEGF )  level  in the cord blood of healthy and Preeclamptic ( PEc ) pregnant women and to associate this with Preeclamptic pregnancy.Material and Methods: A case-control study ofUmbilical cord serum VEGF levels from women with uncomplicated pregnancies (control group, n=60) and pregnancies complicated by Pre-eclampsia (n=40). VEGF in the cord serum was estimated by SANDWICH Enzyme Linked Immunosorbent Assay method by using ELISA Kit and then compared between the two groups.Results: The mean VEGF concentrations in the women who had pre-eclampsia  (578.62±468.3)  were lower than in the control group( 625.75±533.1) , but the difference was not statistically significant ( p= 0.8548).  Conclusion VEGF plays a key role in the instability between endothelial dysfunction and angiogenesis that occurs during Preeclampsia.  VEGF levels might be a useful tool for the early diagnosis of Pre-eclampsia.Asian Journal of Medical Sciences Vol.8(1) 2017 21-25


2012 ◽  
Vol 27 (2) ◽  
pp. 185-192 ◽  
Author(s):  
Conceição Aparecida Dornelas ◽  
Francisco Vagnaldo Fechine-Jamacaru ◽  
Irineu Lima Albuquerque ◽  
Hemerson Iury Ferreira Magalhães ◽  
Adjair Jairo Silva de Souza ◽  
...  

PURPOSE: To determine the effects of green propolis extracted in L-lysine (WSDP) and of L- lysine for 40 weeks on induced rat bladder carcinogenesis. METHODS: The animals (groups I, II, III, IV, V and VI) received BBN during 14 weeks. Group I was treated with propolis 30 days prior received BBN, and then these animals were treated daily with propolis; Groups II and III was treated with subcutaneous and oral propolis (respectively) concurrently with BBN. The animals of Group IV were treated L-lysine; Group V received water subcutaneous; and Group VI received only to BBN. Among the animals not submitted to carcinogenesis induction, Group VII received propolis, Group VIII received L-lysine and Group IX received water. RESULTS: The carcinoma incidence in Group I was lower than that of control (Group VI). The carcinoma multiplicity in Group IV was greater than in Group VI. All animals treated with L-lysine developed carcinomas, and they were also more invasive in Group IV than in controls. On the other hand, Group VIII showed no bladder lesions. CONCLUSION: The WSDP is chemopreventive against rat bladder carcinogenesis, if administered 30 days prior to BBN , and that L-lysine causes promotion of bladder carcinogenesis.


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