scholarly journals Dexmedetomidine Ameliorate CLP-Induced Rat Intestinal Injury via Inhibition of Inflammation

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Yanqing Chen ◽  
Liyan Miao ◽  
Yusheng Yao ◽  
Weilan Wu ◽  
Xiaodan Wu ◽  
...  

The aim was to verify that dexmedetomidine (DEX) can attenuate CLP-induced intestinal injury via inhibition of inflammation. Male Sprague-Dawley (SD) rats were randomly allocated into Sham group and the other three CLP model groups, in terms of different treatments: placebo, DEX, and yohimbine plus DEX (DEX + YOH) groups. Pathology examination was conducted with HE stain. To identify differences among groups, the levels of DAO, and D-lactate in serum were measured by spectrophotometry, and the levels of TNF-α, IL-1β, and IL-6 in serum and organ were measured by ELISA. The expressions of occludin and TLR4 in tissue were detected by Western blot. The survival rate of an additional group of animals within 7 d was recorded. In DEX group, mortality was lower, histology change was minor, DAO, and D-lactate levels were reduced, and occludin expression was increased; the expressions of TNF-α, IL-1β, IL-6, and TLR4 were also decreased in DEX group. These results indicated that acute intestinal injury induced by CLP was mitigated by DEX treatment. However, these effects of DEX were significantly attenuated by yohimbine in DEX + YOH group. Our study indicated the protective effects of DEX on CLP-induced injury, which may be associated with the inhibition of inflammation via modulating TLR4 pathway and can be blocked by yohimbine.

2019 ◽  
Vol 38 (11) ◽  
pp. 1275-1282
Author(s):  
A Pergel ◽  
L Tümkaya ◽  
MK Çolakoğlu ◽  
G Demiral ◽  
S Kalcan ◽  
...  

Carbon tetrachloride (CCL4) is often employed in the production of chlorofluorocarbons, petroleum refining, oil and rubber processing, and laboratory applications. Oral, subcutaneous, and inhalation exposure to CCL4 in animal studies have been shown to be capable of leading to various types of cancer (benign and malignant, liver, breast, and adrenal gland tumors). The present study also evaluated the protective role of infliximab (INF) against the deleterious effects of CCL4 on the intestinal system. Twenty-four male Sprague-Dawley rats were randomly assigned into three groups, control ( n = 8), CCL4 ( n = 8), and CCL4 + INF ( n = 8). The control group received 1 mL isotonic saline solution only via intraperitoneal (i.p.) injection. The CCL4 group received a single i.p. dose of 2 mL/kg CCL4. The CCL4 + INF group received a single i.p. dose of 7 mg/kg INF followed 24 h later by a single dose of 2 mL/kg CCL4. All rats were euthanized 2 days following drug administration. CCL4 group samples also exhibited diffuse loss of enterocytes, vascular congestion, neutrophil infiltration, an extension of the subepithelial space and significant epithelial lifting along the length of the villi with a few denuded villous tips. In addition, CCL4 treatment increased intestinal malondialdehyde (MDA) level and caspase-3 positivity. On the other hand, INF decreased MDA levels, caspase-3 positivity, and loss of villous. Our findings suggest that CCL4 appears to exert a highly deleterious effect on the intestinal mucosa. On the other hand, INF is effective in preventing this CCL4-induced intestinal injury by reducing oxidative stress and apoptosis.


Nanoscale ◽  
2020 ◽  
Vol 12 (42) ◽  
pp. 21599-21604
Author(s):  
Yi Li ◽  
Hong Yu ◽  
Liang Zhao ◽  
Yuting Zhu ◽  
Rui Bai ◽  
...  

Caspase3 gene silencing based on the gene transfer carrier F-CNT-siCas3 had obvious protective effects on myocardial cell apoptosis, ventricular remodeling, and cardiac function in Sprague-Dawley (SD) rats after coronary artery ligation.


2020 ◽  
Vol 7 ◽  
Author(s):  
László Juhász ◽  
Attila Rutai ◽  
Roland Fejes ◽  
Szabolcs P. Tallósy ◽  
Marietta Z. Poles ◽  
...  

Introduction: Sepsis is a dysregulated host response to infection with macro- and microhemodynamic deterioration. Kynurenic acid (KYNA) is a metabolite of the kynurenine pathway of tryptophan catabolism with pleiotropic cell-protective effects under pro-inflammatory conditions. Our aim was to investigate whether exogenously administered KYNA or the synthetic analog SZR-72 affects the microcirculation and mitochondrial function in a clinically relevant rodent model of intraabdominal sepsis.Methods: Male Sprague–Dawley rats (n = 8/group) were subjected to fecal peritonitis (0.6 g kg−1 feces ip) or a sham operation. Septic animals were treated with sterile saline or received ip KYNA or SZR-72 (160 μmol kg−1 each) 16 and 22 h after induction. Invasive monitoring was performed on anesthetized animals to evaluate respiratory, cardiovascular, renal, hepatic and metabolic dysfunctions (PaO2/FiO2 ratio, mean arterial pressure, urea, AST/ALT ratio and lactate levels, respectively) based on the Rat Organ Failure Assessment (ROFA) score. The ratio of perfused vessels (PPV) of the ileal serosa was quantified with the intravital imaging technique. Complex I- and II-linked (CI; CII) oxidative phosphorylation capacities (OXPHOS) and mitochondrial membrane potential (ΔΨmt) were evaluated by High-Resolution FluoRespirometry (O2k, Oroboros, Austria) in liver biopsies. Plasma endothelin-1 (ET-1), IL-6, intestinal nitrotyrosine (NT) and xanthine oxidoreductase (XOR) activities were measured as inflammatory markers.Results: Sepsis was characterized by an increased ROFA score (5.3 ± 1.3 vs. 1.3 ± 0.7), increased ET-1, IL-6, NT and XOR levels, and decreased serosal PPV (65 ± 12% vs. 87 ± 7%), ΔΨmt and CI–CII-linked OXPHOS (73 ± 16 vs. 158 ± 14, and 189 ± 67 vs. 328 ± 81, respectively) as compared to controls. Both KYNA and SZR-72 reduced systemic inflammatory activation; KYNA treatment decreased serosal perfusion heterogeneity, restored PPV (85 ± 11%) and complex II-linked OXPHOS (307 ± 38), whereas SZR-72 improved both CI- and CII-linked OXPHOS (CI: 117 ± 18; CII: 445 ± 107) without effects on PPV 24 h after sepsis induction.Conclusion: Treatment with SZR-72 directly modulates mitochondrial respiration, leading to improved conversion of ADP to ATP, while administration of KYNA restores microcirculatory dysfunction. The results suggest that microcirculatory and mitochondrial resuscitation with KYNA or the synthetic analog SZR-72 might be an appropriate supportive tool in sepsis therapy.


Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1222 ◽  
Author(s):  
Salvatore Benvenga ◽  
Herbert R. Marini ◽  
Antonio Micali ◽  
Jose Freni ◽  
Giovanni Pallio ◽  
...  

Cadmium (Cd) damages the thyroid gland. We evaluated the effects of myo-inositol (MI), seleno-L-methionine (Se) or their combination on the thyroids of mice simultaneously administered with Cd chloride (CdCl2). Eighty-four male mice were divided into 12 groups (seven mice each). Six groups (controls) were treated with 0.9% NaCl (vehicle), Se (0.2 mg/kg/day), Se (0.4 mg/kg/day), MI (360 mg/kg/day), MI+Se (0.2 mg/kg) and MI+Se (0.4 mg/kg). The other six groups were treated with CdCl2 (2 mg/kg), CdCl2+MI, CdCl2+Se (0.2 mg/kg), CdCl2+Se (0.4 mg/kg), CdCl2+MI+Se (0.2 mg/kg) and CdCl2+MI+Se (0.4 mg/kg). An additional group of CdCl2-challenged animals (n = 7) was treated with resveratrol (20 mg/kg), an effective and potent antioxidant. All treatments lasted 14 days. After sacrifice, the thyroids were evaluated histologically and immunohistochemically. CdCl2 reduced the follicular area, increased the epithelial height, stroma, and cells expressing monocyte chemoattractant protein-1 (MCP-1) and C-X-C motif chemokine 10 (CXCL10). CdCl2+Se at 0.2/0.4 mg/kg insignificantly reversed the follicular and stromal structure, and significantly decreased the number of MCP-1 and CXCL10-positive cells. CdCl2+MI significantly reversed the thyroid structure and further decreased the number of MCP-1 and CXCL10-positive cells. CdCl2+MI+Se, at both doses, brought all indices to those of CdCl2-untreated mice. MI, particularly in association with Se, defends mice from Cd-induced damage. The efficacy of this combination was greater than that of resveratrol, at least when using the follicular structure as a read-out for a comparison. We suggest that the use of these nutraceuticals, more specifically the combination of MI plus SE, can protect the thyroid of Cd-exposed subjects.


2021 ◽  
Author(s):  
Suyan Li ◽  
Fenyan Zhang ◽  
Yiguang Lin ◽  
Xiaoli Niu ◽  
Jian Lv ◽  
...  

Abstract Background Accumulating evidence suggests that the intestinal flora is involved in many neurodegenerative diseases. Sepsis can lead to severe intestinal flora imbalance and brain dysfunction. In this study, we investigated Sennoside A may relieve lipopolysaccharide(LPS)-associated encephalopathy via its effect on the gut microbiota in rats. Methods Adult male Sprague-Dawley (SD) rats and germ free (GF) rats were used. The ordinary and germ free SD rats were adopted as a LPS-associated encephalopathy model with or without Sennoside A administration. We investigated gut microbiota diversity and structure, conducted electroencephalograms (EEG) and measured the levels of TNF-α, IL-1β and IL-6 in the cortexes of Sprague Dawley (SD) rats with or without Sennoside A administration. Horizontal fecal microbiota transplantation (FMT) and germ-free rats were used to confirm the important roles of gut microbiota in the mitigation of LPS-associated encephalopathy in rats after Sennoside A supplementation. Results We found that Sennoside A treatment markedly improved brain function in septic rats including decreased ratios of abnormal EEG and lowered levels of TNF-α, IL-1β, and IL-6 in the rat cortexes. While the gut microbiota changed in septic SD rats, Sennoside A improved gut microbial composition, which might mediate its brain protective effects in sepsis. Sennoside A also reduced inflammation in the cortexes of septic rats via gut microbiota improvement. In germ-free rats that received lipopolysaccharide(LPS),Sennoside A could not lower the ratios of abnormal EEG, and could not alleviate TNF-α, IL-1β, and IL-6 levels in the rats’ cortexes. FMT lowered the ratios of abnormal EEG and alleviate TNF-α, IL-1β, and IL-6 levels in rats’ cortexes, which confirmed our hypothesis that the effect of Sennoside A on the improvement of LPS-associated encephalopathy through gut microbiota. Conclusion Our data confirm our hypothesis that Sennoside A likely exerts its brain protective effects through gut microbiota alteration.


2016 ◽  
Vol 57 (6) ◽  
pp. 627-636 ◽  
Author(s):  
Ling Zhou ◽  
Baoquan Wan ◽  
Xingfa Liu ◽  
Yemao Zhang ◽  
Jinsheng Lai ◽  
...  

Abstract A 50-Hz magnetic field (MF) is a potential health-risk factor. Its effects on the cardiovascular system have not been fully investigated. This study was conducted to explore the effects of long-term exposure to a 50-Hz MF on the cardiovascular system. In the study, an exposure system was constructed, and the distribution of the 50-Hz MF was determined. Sixty-four Sprague-Dawley (SD) rats were exposed to a 50-Hz MF at 100 μT for 24 weeks, 20 h per day, while another 64 rats were sham exposed. During the exposure, blood pressure was measured every 4 weeks. After 24 weeks, echocardiography, cardiac catheterization and electrocardiography were performed. Moreover, heart and body weight were recorded, and haematoxylin–eosin staining and real-time PCR were conducted. The results showed that compared with the sham group, exposure to a 50-Hz MF did not exert any effects on blood pressure, pulse rate, heart rate or cardiac rhythm. Furthermore, echocardiography and cardiac catheterization showed that there were no significant differences in the cardiac morphology or haemodynamics. In addition, histopathological examination showed that exposure to a 50-Hz MF had no effects on the structure of the heart. Finally, expression of the cardiac hypertrophy–related genes did not show any significant differences between the 50-Hz MF exposure group and the sham group. Taken together, in SD rats, exposure to a 50-Hz/100 μT MF for 24 weeks did not show any obvious effects on the cardiovascular system.


2013 ◽  
Vol 2013 ◽  
pp. 1-4 ◽  
Author(s):  
Xian Shi ◽  
Yuxian Zhong ◽  
Jiarui Yao ◽  
Sen Hu ◽  
Lu Wang ◽  
...  

Sixty Sprague-Dawley rats were divided into 5 groups: (a) control group (HS); (b) Immediate rehydration group (IFR); (c) ST36 electroacupuncture (EA) delay rehydration group (EA/DFR): EA at ST36 immediately after blood loss with infusion 3 h later; (d) EA nonmeridian rehydration group (SEA/DFR): EA at nonacupuncture sites with rehydration similar to EA/DFR; (e) ST36 EA group (EA): EA at ST36 immediately after blood loss with no rehydration. Forty-five percent of the entire blood volume was taken out to make lethal hemorrhagic shock models. We recorded the survival rate, intestinal tissue DAO content, and microcirculation. The survival rate of the EA/DFR group and the IFR group was significantly higher than that of the other three groups (P<0.05). Twelve hours after blood loss, intestinal tissue DAO content of the EA/DFR group and the IFR group was significantly higher than that of the SEA/DFR group, EA group, and HS group (P<0.05andP<0.01). The mucosal blood flow of the EA/DFR group and the IFR group was significantly higher than the other groups (P<0.05each). We conclude that EA improves the blood pressure and raises the early survival rate of hemorrhagic shock rats, maintains the intestinal barrier function, and improves the degree of intestinal ischemia.


Author(s):  
Yating Qin ◽  
Chao Lv ◽  
Xinxin Zhang ◽  
Weibin Ruan ◽  
Xiangyu Xu ◽  
...  

Anthracyclines, such as doxorubicin (DOX), are among the effective chemotherapeutic drugs for various malignancies. However, their clinical use is limited by irreversible cardiotoxicity. This study sought to determine the role of neuraminidase 1 (NEU1) in DOX-induced cardiomyopathy and the potential cardio-protective effects of NEU1 inhibitor oseltamivir (OSE). Male Sprague–Dawley (SD) rats were randomized into three groups: control, DOX, and DOX + OSE. NEU1 was highly expressed in DOX-treated rat heart tissues compared with the control group, which was suppressed by OSE administration. Rats in the DOX + OSE group showed preserved cardiac function and were protected from DOX-induced cardiomyopathy. The beneficial effects of OSE were associated with the suppression of dynamin-related protein 1 (Drp1)-dependent mitochondrial fission and mitophagy. In detail, the elevated NEU1 in cardiomyocytes triggered by DOX increased the expression of Drp1, which subsequently enhanced mitochondrial fission and PINK1/Parkin pathway-mediated mitophagy, leading to a maladaptive feedback circle towards myocardial apoptosis and cell death. OSE administration selectively inhibited the increased NEU1 in myocardial cells insulted by DOX, followed by reduction of Drp1 expression, inhibition of PINK1 stabilization on mitochondria, and Parkin translocation to mitochondria, thus alleviating excessive mitochondrial fission and mitophagy, alleviating subsequent development of cellular apoptotic process. This work identified NEU1 as a crucial inducer of DOX-induced cardiomyopathy by promoting Drp1-dependent mitochondrial fission and mitophagy, and NEU1 inhibitor showed new indications of cardio-protection against DOX cardiotoxicity.


Author(s):  
Stephanie M. Himmler ◽  
Brett T. Himmler ◽  
Rafał Stryjek ◽  
Klaudia Modlińska ◽  
Wojciech Pisula ◽  
...  

During play fighting, rats attack and defend the nape and during the course of this competitive interaction, they may adopt a configuration in which one animal stands over its supine partner (i.e., pin). Because the pin configuration is typically frequent and relatively easy to identify, it has been widely used as a marker to detect the effects of experimental treatments. In the present study, the frequency of pinning during standardized, 10min trials in three strains of rats, Long Evans hooded (LE), Sprague-Dawley (SD) and wild (WWCPS), was compared. LE and SD had higher rates than WWCPS rats (#/min: 6.5, 5.5, 1.5, respectively). When adjusted for strain differences in the frequency of attacks, SD as well as WWCPS rats had lower rates of pinning compared to LE rats. Both SD and WWCPS rats were less likely to use tactics of defense that promote pinning. Moreover, while the majority of the pins achieved in LE rats arose from the defender actively rolling over onto its back, the majority of pins in WWCPS rats arose because one partner pushed the other onto its back. SD rats were intermediate in this regard. Finally, once they do adopt the pin configuration, SD rats are less likely to remain supine than LE and WWCPS rats. That is, both SD and WWCPS rats have significantly fewer pins than LE rats, but a different combination of factors account for this. These data highlight the need to use a battery of measures for ascertaining the effects of experimental manipulations on play. Some suggested guidelines are provided.


2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Michael Buenor Adinortey ◽  
Charles Ansah ◽  
Benjamin Aboagye ◽  
Justice Kwabena Sarfo ◽  
Orleans Martey ◽  
...  

Dissotis rotundifolia is a plant in the family Melastomataceae. The methanolic extract of the whole plant is reported to be rich in C-glycosylflavones such as vitexin and orientin. Though there are several reports on the ethnomedicinal use of this plant extract in stomach ulcers, experimental-based data is unavailable. The drive for carrying out this research was to obtain data on the possible ameliorative effect of the whole plant extract of Dissotis rotundifolia (DRE) in gastric ulcerations induced by ethanol in Sprague Dawley (SD) rats. SD rats were pretreated with 100, 300, and 500 mg/kg of DRE for 14 days after which an ulcerogen-ethanol was administered. Gross examinations of the stomach lining and histological analysis of gastric lesions were carried out coupled with an assessment of the antioxidant activity of gastric mucosa using MDA, GSH, CAT, and SOD as indicators. The data suggested a significant attenuation in gastric mucosal damage in DRE-pretreated ethanol-induced gastric ulcer reflected in the antioxidant status. There was also a reduction or absence of hemorrhage, edema, and leucocytes infiltration in DRE-treated groups compared to the negative control group. DRE conserved glutathione (GSH) levels, reduced malondialdehyde (MDA) levels, and enhanced catalase (CAT) and superoxide dismutase (SOD) enzyme levels. The present study shows that DRE possess protective effects against ethanol-induced ulcer damage in the stomach of rats, which could be attributed to its antioxidant activity.


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