scholarly journals Resolvin D1 Reduces the Immunoinflammatory Response of the Rat Eye following Uveitis

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Rossi Settimio ◽  
Di Filippo Clara ◽  
Ferraraccio Franca ◽  
Simonelli Francesca ◽  
D'Amico Michele

This study investigated whether the administration of resolvin D1 to rats with endotoxininduced uveitis (EIU) ameliorates the immuno-inflammatory profile of the eye. 24 h after the administration of 200 μg LPS into the footpad of Sprague-Dawley rats, severe changes of the structure of the eye occurred concomitantly with a severe inflammatory and immune response. These latter included strong infiltration of PMN leukocytes CD11b+T-lymphocytes CD4+and CD8+within the eye and a significant release of the cytokines/chemokines TNF-alpha, CXCL8, and RANTES too. Bolus of resolvin D1 (RvD1; 10–100–1000 ng/kg in 200 μL of sterile saline via the tail vein) significantly and dose-dependently (i) reduced the development of the ocular derangement caused by LPS; (ii) reduced the clinical score attributed to EIU; (iii) reduced the protein concentration and myeloperoxidase activity (MPO) in aqueous humor (AqH); and (iv) reduced neutrophils, T-lymphocytes, and cytokines within the eye.

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
S. Rossi ◽  
C. Di Filippo ◽  
C. Gesualdo ◽  
N. Potenza ◽  
A. Russo ◽  
...  

This study investigated the protective effects of intravitreal Resolvin D1 (RvD1) against LPS-induced rat endotoxic uveitis (EIU). RvD1 was administered into the right eye at a single injection of 5 μL volume containing 10–100–1000 ng/kg RvD1 1 h post-LPS injection (200 μg,Salmonella minnesota) into thefootpad of Sprague-Dawley rats. 24 h later, the eye was enucleated and examined for clinical, biochemical, and immunohistochemical evaluations. RvD1 significantly and dose-dependently decreased the clinical score attributed to EIU, starting from the dose of 10 ng/kg and further decreased by 100 and 1000 ng/kg. These effects were accompanied by changes in four important determinants of the immune-inflammatory response within the eye: (i) the B and T lymphocytes, (ii) the miRNAs pattern, (iii) the ubiquitin-proteasome system (UPS), and (iv) the M1/M2 macrophage phenotype. LPS+RvD1 treated rats showed reduced presence of B and T lymphocytes and upregulation of miR-200c-3p, miR 203a-3p, miR 29b-3p, and miR 21-5p into the eye compared to the LPS alone. This was paralleled by decreases of the ubiquitin, 20S and 26S proteasome subunits, reduced presence of macrophage M1, and increased presence of macrophage M2 in the ocular tissues. Accordingly, the levels of the cytokine TNF-α, the chemokines MIP1-αand NF-κB were reduced.


2006 ◽  
Vol 74 (7) ◽  
pp. 4387-4389 ◽  
Author(s):  
Rachel Marion ◽  
Asiya Baishanbo ◽  
Gilles Gargala ◽  
Arnaud François ◽  
Philippe Ducrotté ◽  
...  

ABSTRACT In 5-day-old immunocompetent Sprague-Dawley rats infected with either 102 or 105 Cryptosporidium parvum oocysts, transient infection resulted 120 days later in increased cardiovascular depressor response to jejunal distension and jejunal myeloperoxidase activity (P < 0.05). Nitazoxanide treatment normalized jejunal sensitivity (P < 0.001) but not myeloperoxidase levels (P > 0.05). Data warrant further evaluation of the role of early cryptosporidiosis in the development of chronic inflammatory gut conditions.


2018 ◽  
Vol 9 (1) ◽  
pp. 31-40 ◽  
Author(s):  
Jing Shi ◽  
Guofeng Wu ◽  
Xiaohua Zou ◽  
Ke Jiang

Background/Aims: Cardiac surgery-associated acute kidney injury (CSA-AKI) is one of the most common postoperative complications in intensive care medicine. Baicalin has been shown to have anti-inflammatory and antioxidant roles in various disorders. We aimed to test the protective effects of baicalin on CSA-AKI using a rat model. Methods: Sprague-Dawley rats underwent 75 min of cardiopulmonary bypass (CPB) with 45 min of cardioplegic arrest (CA) to establish the AKI model. Baicalin was administered at different doses intragastrically 1 h before CPB. The control and treated rats were subjected to the evaluation of different kidney injury index and inflammation biomarkers. Results: Baicalin significantly attenuated CPB/CA-induced AKI in rats, as evidenced by the lower levels of serum creatinine, serum NGAL, and Kim1. Baicalin remarkably inhibited oxidative stress, reflected in the decreased malondialdehyde and myeloperoxidase activity, and enhanced superoxide dismutase activity and glutathione in renal tissue. Baicalin suppressed the expression of IL-18 and iNOS, and activated the Nrf2/HO-1 pathway. Conclusion: Our data indicated that baicalin mediated CPB/CA-induced AKI by decreasing the oxidative stress and inflammation in the renal tissues, and that baicalin possesses the potential to be developed as a therapeutic tool in clinical use for CSA-AKI.


PPAR Research ◽  
2010 ◽  
Vol 2010 ◽  
pp. 1-13 ◽  
Author(s):  
Enrico Briguglio ◽  
Rosanna Di Paola ◽  
Irene Paterniti ◽  
Emanuela Mazzon ◽  
Giacomo Oteri ◽  
...  

We have investigated the effects of WY14643, a potent peroxisome proliferator activator receptor-α(PPAR-α) agonist, in a rat model of ligature-induced periodontitis. Male Sprague-Dawley rats were lightly anaesthetized with pentobarbitone (35 mg/kg). Sterile, 2-0 black braided silk thread was placed around the cervix of the lower left first molar and knotted medially. Animals received WY14643 (1 mg/kg i.p, daily for eight days). Eighths days after placement of the ligature, we evaluated several markers of inflammation such us (1) myeloperoxidase activity, (2) a cytokines and adhesion molecules expression, (3) NF-κB expression, (4) iNOS expression, (5) the nitration of tyrosine residues, (6) activation of the nuclear enzyme poly(ADP-ribose) polymerase, (7) apoptosis, and (8) the degree of gingivomucosal tissues injury. Administration of WY14643 significantly decreased all of the parameters of inflammation as described above. These results demonstrate that WY14643 exerts an anti-inflammatory role during experimental periodontitis and is able to ameliorate the tissue damage.


2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
S. Rossi ◽  
C. Di Filippo ◽  
C. Gesualdo ◽  
F. Testa ◽  
M. C. Trotta ◽  
...  

Rat endotoxin-induced uveitis (EIU) is a well-established model of human uveitis. In this model, intravitreal injection of resolvin D1 (RvD1, 10–100–1000 ng/kg) 1 hour after subcutaneous treatment of Sprague-Dawley rats with lipopolysaccharide (LPS, 200 μg/rat) significantly prevented the development of uveitis into the eye. RvD1 dose-dependently increased the expression of sirtuin-1 (SIRT1) within the eye, while it decreased the expression of acetyl-p53 and acetyl-FOXO1. These effects were accompanied by local downregulation of some microRNAs related to the expression and activity of SIRT1. These were miR-195-5p, miR-200a-3p, miR-34a-5p, and miR-145-5p. An increase of manganese superoxide dismutase and decrease of caspase 3 were evident after RvD1 treatment. In another set of experiments, the protective effects of RvD1 (1000 ng/kg) were partly abolished by the pretreatment of the rats with EX527 (10 mg/kg/day, i.p.), a specific inhibitor of SIRT1 activity, for 7 days prior to the induction of EIU in rats. Similarly, the effects of RvD1 (1000 ng/kg) on the SIRT1 protein expression were abolished by Boc2,N-t-butoxycarbonyl-PLPLP, a specific formyl-peptide receptor type 2/lipoxin A receptor antagonist. Therefore, an interplay of the SIRT1 activity on the RvD1 mediated resolution of EIU is argued.


2005 ◽  
Vol 288 (6) ◽  
pp. E1082-E1088 ◽  
Author(s):  
Thaddeus W. W. Pace ◽  
Robert L. Spencer

Glucocorticoid negative feedback regulation of the hypothalamic-pituitary-adrenal (HPA) axis is mediated by corticosteroid receptors. It is widely thought that during stress, glucocorticoid receptors (GR) are essential for this negative feedback. In contrast, mineralocorticoid receptors (MR) are associated with HPA axis regulation in basal, nonstress conditions. Notions about the relative roles of MR and GR for HPA axis regulation during stressor challenge may not be complete. Recent work in our laboratory suggests that previous estimates of MR occupancy at resting plasma levels of corticosterone (CORT) may be overestimated. It is possible that a significant number of MR may be available to mediate negative feedback during stressor challenge. We hypothesized that this may be especially the case during mild stressor challenge when the plasma CORT response is weak. In the present studies, adult male Sprague-Dawley rats were first treated systemically or centrally with the selective MR antagonist RU28318 (50 mg/kg sc or 500 ng·10 μl−1·2 h−1 icv) or vehicle (300 μl propylene glycol sc or 10 μl/2 h sterile saline icv) and then challenged with 60-min novel environment or restraint. In vehicle controls, restraint resulted in a greater plasma CORT response than novel environment. Both systemic and central treatment with RU28318 significantly increased CORT responding to novel environment relative to vehicle controls. However, RU28318 treatment did not increase the CORT response to restraint. These data suggest that MR may be necessary for glucocorticoid regulation of HPA axis activity during mild stressors, but not during stressors that result in a more robust CORT response.


Author(s):  
Leslie A Stewart ◽  
Denise M Imai ◽  
Laurel Beckett ◽  
Yueju Li ◽  
K C Lloyd ◽  
...  

An extended-release formulation of the NSAID meloxicam (MSR) is used to provide 72 h of continuous analgesia in many species, including rodents. Although standard formulations of meloxicam are frequently used in rats with no observable injection-site reactions, the potential adverse effects from MSR have not been characterized sufficiently nor has a prospective study of these effects been performed in rats. To address this deficiency, we evaluated injection-site reactions after a single subcutaneous administration of MSR (n = 16) or sterile saline (SC, n = 6) in the flank of age- and sex-matched Sprague–Dawley rats. Mass and erythema scores were measured daily for 2 wk, and injection sites were collected for histopathology after euthanasia. Rats were randomly selected for euthanasia at 7 d (n = 12) or 14 d (n = 10) after injection to capture the subacute and chronic phases of mass and erythematic lesion formation. No rats in the SC group developed lesions, whereas all 16 MSR-treated rats developed masses. The median time to first mass in the MSR treatment group was 3 d (95% CI, 2–3 d), and nearly 8 d for erythema (95% CI, 6.7–9.1 d). The trajectory of mass lesion severity showed rapid progression from score 1 at onset (day 2 or 3) to score 2 for almost all animals by day 5 or 6. Histopathology was characterized by localized inflammation with central necrosis and peripheral fibrosis, with some sections showing developing draining tracts. Given the high prevalence and severity of localized skin reactions, MSR analgesia should be considered carefully for Sprague–Dawley rats.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Wei-Chi Chou ◽  
Ming-Chang Kao ◽  
Chung-Tai Yue ◽  
Pei-Shan Tsai ◽  
Chun-Jen Huang

Reperfusion of ischemic limbs can induce inflammation and subsequently cause acute lung injury. Caffeine, a widely used psychostimulant, possesses potent anti-inflammatory capacity. We elucidated whether caffeine can mitigate lung inflammation caused by ischemia-reperfusion (IR) of the lower limbs. Adult male Sprague-Dawley rats were randomly allocated to receive IR, IR plus caffeine (IR + Caf group), sham-operation (Sham), or sham plus caffeine (n=12in each group). To induce IR, lower limbs were bilaterally tied by rubber bands high around each thigh for 3 hours followed by reperfusion for 3 hours. Caffeine (50 mg/kg, intraperitoneal injection) was administered immediately after reperfusion. Our histological assay data revealed characteristics of severe lung inflammation in the IR group and mild to moderate characteristic of lung inflammation in the IR + Caf group. Total cells number and protein concentration in bronchoalveolar lavage fluid of the IR group were significantly higher than those of the IR + Caf group (P<0.001andP=0.008, resp.). Similarly, pulmonary concentrations of inflammatory mediators (tumor necrosis factor-α, interleukin-1β, and macrophage inflammatory protein-2) and pulmonary myeloperoxidase activity of the IR group were significantly higher than those of the IR + Caf group (allP<0.05). These data clearly demonstrate that caffeine could mitigate lung inflammation induced by ischemia-reperfusion of the lower limbs.


1996 ◽  
Vol 270 (5) ◽  
pp. G821-G825 ◽  
Author(s):  
K. Tjandra ◽  
P. Kubes ◽  
K. Rioux ◽  
M. G. Swain

Since glucocorticoids have been shown to inhibit leukocyte accumulation to inflammatory sites (6,9) and endogenous glucocorticoid levels are elevated in our cholestatic rat model, we investigated their role during acute inflammation. Sprague-Dawley rats (150-200 g) were either bile duct resected (BDR) or sham resected (sham). Five days later, a 2% carrageenan solution in saline was injected subcutaneously into preformed air pouches on their backs. Animals were killed 5 h later, and inflammatory response was quantitated by measuring the exudate volume, cell count, and myeloperoxidase (mainly in neutrophils) activity. We also pretreated BDR/sham rats with RU-486 (2 mg/kg ip), a glucocorticoid receptor antagonist, 1 h before carrageenan injection. BDR rats exhibited an impaired inflammatory response reflected by 20, 52, and 42% decreases in exudate volume, cell count, and myeloperoxidase activity, respectively (all P ⊂ 0.05). RU-486 treatment significantly increased the inflammatory response in BDR rats (to sham levels), but not in sham rats. These results suggest that endogenous glucocorticoid suppresses the inflammatory response in BDR rats.


2007 ◽  
Vol 23 (8) ◽  
pp. 471-477 ◽  
Author(s):  
M Sandikci ◽  
U Eren ◽  
S Kum

The aim of this study was to determine the localization and number of CD4- and CD8-positive T lymphocytes in bronchus-associated lymphoid tissue (BALT) of the embryos and newborns or young and adult rats exposed to formaldehyde (6 ppm), technical xylene (300 ppm), or a combination of these two agents (3 ppm + 150 ppm) for 6 weeks (8 h/day). A total of 96 female Sprague-Dawley rats were used. The CD4-positive cells were localized predominately in area under the epithelium and in the periphery of BALT follicles after the exposure period. However, CD8-positive cells were localized mainly in the periphery of BALT follicles after the exposure period. The number of CD4- and CD8-positive lymphocytes significantly increased in exposed young and adult rats compared to the respective controls. These results suggest that formaldehyde and/or xylene may affect the local immunity in BALT particularly in young and adult rats.


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