scholarly journals Autophagy Alters Bladder Angiogenesis and Improves Bladder Hyperactivity in the Pathogenesis of Ketamine-Induced Cystitis in a Rat Model

Biology ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 488
Author(s):  
Jian-He Lu ◽  
Yi-Hsuan Wu ◽  
Tai-Jui Juan ◽  
Hung-Yu Lin ◽  
Rong-Jyh Lin ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Inflammatory Responses ◽  
Interstitial Fibrosis ◽  
Contractile Activity ◽  
White Blood Cells ◽  
Capillary Density ◽  
Bladder Function ◽  
Control Group ◽  
Sprague Dawley ◽  
Antiangiogenic Effect

The present study attempts to elucidate whether autophagy alters bladder angiogenesis, decreases inflammatory response, and ameliorates bladder hyperactivity—thereby influencing bladder function in ketamine-induced cystitis (KIC). In our methodology, female Sprague-Dawley (S-D) rats were randomly divided into the control group, the ketamine group, the ketamine+rapamycin group, and the ketamine+wortmannin group. The bladder function, contractile activity of detrusor smooth muscle, distribution of autophagosome and autolysosome, total white blood cells (WBCs) and leukocyte differential counts, the expressions of autophagy-associated protein, angiogenesis markers, and signaling pathway molecules involved in KIC were tested, respectively. The data revealed that treatment with ketamine significantly results in bladder overactivity, enhanced interstitial fibrosis, impaired endothelium, induced eosinophil-mediated inflammation, swelling, and degraded mitochondria and organelles, inhibited angiogenesis, and elevated the phosphorylation of Akt. However, treatment with rapamycin caused an inhibitory effect on vascular formation, removed ketamine metabolites, decreased the eosinophil-mediated inflammation, and ameliorated bladder hyperactivity, leading to improve bladder function in KIC. Moreover, wortmannin treatment reduced basophil-mediated inflammatory response, improved bladder angiogenesis by increasing capillary density and VEGF expression, to reverse antiangiogenic effect to repair KIC. In conclusion, these findings suggested that autophagy could modulate inflammatory responses and angiogenesis, which improved bladder function in KIC.

Role of leukocytes in reperfusion injury of skeletal muscle after partial ischemia

1989 ◽  
Vol 257 (4) ◽  
pp. H1068-H1075 ◽  
Author(s):  
J. Yokota ◽  
J. P. Minei ◽  
G. A. Fantini ◽  
G. T. Shires
Keyword(s):  
Skeletal Muscle ◽  
Reperfusion Injury ◽  
White Blood Cells ◽  
Creatine Phosphate ◽  
High Energy ◽  
Control Group ◽  
Base Line ◽  
Infrarenal Aorta ◽  
Sprague Dawley ◽  
Membrane Injury

These experiments evaluated the leukocyte as a potential source of oxygen free radical (OFR) generation during reperfusion injury in post-ischemic skeletal muscle. The infrarenal aorta of heparinized Sprague-Dawley rats was clamped for 90 min, declamped, and reperfused for 60 min. Hindlimb muscle resting transmembrane potential difference (Em) and high-energy phosphate content were determined at base line, during ischemia, and on reperfusion. Four groups were studied: a control group, a second group receiving superoxide dismutase and catalase (SOD + CAT) on declamping, a third group receiving dimethylmyleran (DMM) 7 days before the experiment to obtain a selective leukopenia (white blood cells = 1,210 +/- 144/mm3, neutrophils = 1.2%), and a fourth group pretreated with allopurinol (ALLO). During the ischemic period, resting Em was significantly depolarized (-78.6 +/- 0.5 mV from -90.3 +/- 0.3; P less than 0.05) in the control group, whereas creatine phosphate (CP) was depleted and ATP maintained. Data collected during the ischemic phase of the three other groups were similar to the control group (P = NS). On reperfusion, persistent depolarization of resting Em was observed despite restoration of muscle CP content in the control and ALLO groups (-75.4 and -77.0 mV, respectively). In contrast, significant repolarization of resting Em was noted after reperfusion in the SOD + CAT and DMM groups (-86.5 and -88.6 mV, respectively). These data implicate leukocyte-generated OFR as mediators of reperfusion-associated cellular membrane injury in postischemic skeletal muscle.

Effects of danshensu on the transforming growth factor-β1/smads signaling pathway in rats with lung injury

2020 ◽  
Vol 10 (11) ◽  
pp. 1816-1823
Author(s):  
Jing Qin ◽  
Xiaoqiang Zhang ◽  
Shengyan Wang ◽  
Yongming Zhang
Keyword(s):  
Lung Injury ◽  
Mrna Expression ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Abdominal Cavity ◽  
Physiological Saline ◽  
Transforming Growth Factor Β1 ◽  
Control Group ◽  
Sprague Dawley ◽  
Sd Rats

Observe the therapeutic effect of Danshensu on lung injury for rats, as well as explore the mechanism of Danshensu in TGF-β1/Smads signaling. Thirty Sprague-Dawley (SD) rats were intratracheally instilled with bleomycin to induce lung injury and interstitial fibrosis. Divided Thirty rats into three groups. DA group (η = 10): Inject 15 mg/kg Danshensu into the abdominal cavity; DXM group (η = 10): Inject 1 mg/kg dexamethasone into the abdominal cavity; BLM group (η = 10): Inject 2 mL physiological saline into the abdominal cavity. Then ten SD rats were intratracheally instilled with physiological saline as normal control group, NC group: Inject 2 mL physiological saline into the abdominal cavity. After a period of 28 days, the degree of pulmonary alveolitis was evaluated using hematoxylin-eosin (HE) staining, and the degree of lung fibrosis was evaluated using Masson?s trichrome (MT) staining. The immunohistochemistry was used to determine the expression of α-SMA. Magnetic nanoparticles+rtQ-PCR was used to determine the mRNA expressions for TGF-β1, Smad3, and Smad7. The alveolitis and pulmonary fibrosis in DA rats were obviously less than those in BLM rats and DXM rats. The expression of α-SMA in DA rats was obviously less than that of in BLM rats and DXM rats; the mRNA expression of TGF-β1 and Smad3 in DA rats were obviously reduced; the Smad7 mRNA expression was obviously up-regulated. DA can alleviate rat lung injury caused by bleomycin. Inhibiting the TGF-β1 and Smad3 mRNA expression, as well as boosting the Smad7 mRNA expression is one of the mechanisms by which Danshensu reduces lung injury.

scholarly journals Effect of diaspirin cross-linked hemoglobin on normal and postischemic microcirculation of the rat pancreas

1999 ◽  
Vol 276 (6) ◽  
pp. G1507-G1514 ◽  
Author(s):  
Ernst von Dobschuetz ◽  
Tomas Hoffmann ◽  
Clemens Engelschalk ◽  
Konrad Messmer
Keyword(s):  
Detrimental Effect ◽  
Oxygen Carrier ◽  
Capillary Density ◽  
Control Group ◽  
Leukocyte Adherence ◽  
Sprague Dawley ◽  
Rat Pancreas ◽  
Sprague Dawley Rats ◽  
Pancreatic Ischemia ◽  
Complete Restoration

Microcirculatory alterations with reduced nutritive supply to the pancreas could be the cause of hyperamylasemia, which occurs in some patients receiving the vasoactive oxygen carrier diaspirin cross-linked hemoglobin (DCLHb) in clinical studies. Therefore, the effects of DCLHb on rat pancreas microcirculation were evaluated. Anesthetized Sprague-Dawley rats received one of the following treatments during baseline conditions ( n = 7 rats/group): 10% hydroxyethyl starch (HAES) (0.4 ml/kg), DCLHb (400 mg/kg), or DCLHb (1,400 mg/kg). After 1 h of complete, reversible pancreatic ischemia, other animals received 10% HAES (0.4 ml/kg) or DCLHb (400 mg/kg) during the onset of reperfusion. The number of red blood cell-perfused capillaries (functional capillary density, FCD) and the level of leukocyte adherence in postcapillary venules in the pancreas were assessed by means of intravital microscopy during 2 h after treatment. In the nonischemic groups, FCD was 18% greater after DCLHb (1,400 mg/kg) than after 10% HAES treatment without any increase in leukocyte adherence. In the inschemia-reperfusion (I/R) 10% HAES group, FCD was significantly ( P < 0.05) lowered, leukocyte adherence enhanced, and mean arterial pressure (MAP) reduced by 31% compared with nonischemic animals. DCLHb treatment in the I/R group resulted in a slight increase in FCD, a significant ( P < 0.05) reduction of leukocyte adherence, and a complete restoration of MAP compared with the animals of the I/R control group. Thus our data provide no evidence for a detrimental effect on the pancreatic microcirculation or an enhanced risk of postischemic pancreatitis by DCLHb.

scholarly journals Monocytes Undergo Functional Reprogramming to Generate Immunosuppression through HIF-1α Signaling Pathway in the Late Phase of Sepsis

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Li-Li Li ◽  
Bing Dai ◽  
Yu-Han Sun ◽  
Ting-Ting Zhang
Keyword(s):  
Clinical Study ◽  
Inflammatory Response ◽  
Signaling Pathway ◽  
Animal Study ◽  
Inflammatory Responses ◽  
Late Phase ◽  
Severe Pneumonia ◽  
Control Group ◽  
L1 Protein ◽  
Control Injection

Severe pneumonia with sepsis is characterized by a dysregulated inflammatory response of endotoxin. In our study, we attempted to investigate the roles of the immune guardian cells (monocytes) in the immune-inflammatory response of severe pneumonia-induced sepsis. We performed analysis in the blood samples of human and animals with ELISA, western blot, flow cytometry (FCM) methods, etc. Results showed that the proinflammatory status shifted to hypoinflammatory phases during the sepsis process. In a clinical study, the levels of IL-1β, IL-6, TNF-α, etc., except for IL-10, were inhibited in the late phase of sepsis, while, in an animal study, the immune suppression status was attenuated with administration of the adenovirus Ade-HIF-1α. Conversely, the amount of IL-10 was lower in the adenovirus Ade-HIF-1α group compared with the sepsis model group and the Ade-control group. Moreover, in the clinical study, the programmed cell death-ligand 1 (PD-L1) was overexpressed in monocytes in the late phase of sepsis, while the expression of proteins HIF-1α and STAT3 was decreased in the late phase of sepsis. However, in the animal study, we found that the HIF-1α factor facilitated the inflammatory response. The expression of the proteins HIF-1α and STAT3 was increased, and the PD-L1 protein was decreased with the adenovirus Ade-HIF-1α administration compared with the rats without Ade-HIF-1α injection and with the Ade-control injection. Additionally, the proteins HIF-1α and STAT3 were coregulated at transcriptional levels during the inflammatory responses of sepsis. Taken together, monocytes undergo reprogramming to generate immunosuppression through the HIF-1α signaling pathway in the late phase of sepsis.

scholarly journals Proinflammatory Role of Angiotensin II in the Aorta of Normotensive Mice

2019 ◽  
Vol 2019 ◽  
pp. 1-11
Author(s):  
Rariane Silva de Lima ◽  
Juliane Cristina de Souza Silva ◽  
Cintia Taniguti Lima ◽  
Leandro Ezequiel de Souza ◽  
Maikon Barbosa da Silva ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Inflammatory Response ◽  
Inflammatory Responses ◽  
Inflammatory Cells ◽  
Control Group ◽  
Positive Staining ◽  
Perivascular Adipose Tissue ◽  
Local Inflammatory Response ◽  
Applied Dose ◽  
And Migration

Angiotensin II plays important functions in cardiovascular system mediating actions leading to inflammatory responses such as activation of VSMC in order to produce ROS, inflammatory cytokines, chemokines, and adhesion molecules. Changes in angiotensin II production could stimulate the recruitment and activation of myeloid cells initiating local inflammatory response without effect on BP. We aimed to verify if angiotensin II induces an inflammatory response in the aorta and if it correlates with variations in BP. C57Bl/6 mice treated with saline solution (0.9%, control group) or angiotensin II (30ng/kg, Ang II group) were used. BP and HR levels were measured. Immunohistochemistry for IL1-β, TGF-β, iNOS, CD45, andα-actin was performed in the aorta. BP and HR do not change. A biphasic response was observed both for IL1-βand TGF-βexpression and also for the presence of CD45 positive cells, with an acute increase (between 30 and 60 minutes) and a second increase, between 24 and 48 hours. Positive staining for iNOS increased in the earlier period (30 minutes) in perivascular adipose tissue and in a longer period (48 hours) in tunica adventitia. Immunoblotting toα-actin showed no alterations, suggesting that the applied dose of angiotensin II does not alter the aortic VSMCs phenotype. The results suggest that angiotensin II, even at doses that do not alter BP, induces the expression of inflammatory markers and migration of inflammatory cells into the aorta of normotensive mice. Thus, angiotensin II may increase the propensity to develop a cardiovascular injury, even in normotensive individuals.

scholarly journals Effects of Repeated Chlamydia pneumoniae Inoculations on Aortic Lipid Accumulation and Inflammatory Response in C57BL/6J Mice

2005 ◽  
Vol 73 (10) ◽  
pp. 6458-6466 ◽  
Author(s):  
Liisa Törmäkangas ◽  
Leena Erkkilä ◽  
Taina Korhonen ◽  
Terttu Tiirola ◽  
Aini Bloigu ◽  
...  
Keyword(s):  
Heat Shock ◽  
Inflammatory Response ◽  
Lipid Accumulation ◽  
Chlamydia Pneumoniae ◽  
Inflammatory Responses ◽  
Autoimmune Response ◽  
Control Group ◽  
Heat Shock Protein 60 ◽  
Aortic Sinus ◽  
Dna And Rna

ABSTRACT Chlamydia pneumoniae is a common respiratory tract pathogen, and persistent infections have been associated with atherosclerosis. We studied the effects of repeated chlamydial inoculations on the inflammatory response and on aortic lipid accumulation in C57BL/6J mice. Mice fed a diet supplemented with 0.2% cholesterol were infected three or six times with C. pneumoniae every fourth week. Sera and lungs were analyzed for inflammatory responses, lung tissues were tested for the presence of C. pneumoniae DNA and RNA, and intimal lipid accumulation in the aortic sinus was quantified. High levels of chlamydial heat shock protein 60 (Hsp60) immunoglobulin G2c subclass antibodies were detected in all of the infected mice, and a positive and statistically significant correlation was found between these antibodies and autoantibodies against mouse Hsp60. Both Hsp60 antibody levels correlated with the severity of lung tissue inflammation. The cholesterol supplement in the diet had no effect on serum cholesterol levels. Significantly larger intimal lipid lesions were seen in the mouse group infected six times (6,542 μm2) than in the control group (1,376 μm2; P = 0.034). In conclusion, repeated inoculations increased aortic sinus lipid accumulation in normocholesterolemic mice. The correlation between the antibodies to mouse and chlamydial Hsp60 proteins and their association with lung inflammation further support the theory of the development of an autoimmune response against heat shock proteins after repeated chlamydial infections.

scholarly journals Exposure to Nickel Oxide Nanoparticles Induces Acute and Chronic Inflammatory Responses in Rat Lungs and Perturbs the Lung Microbiome

2022 ◽  
Vol 19 (1) ◽  
pp. 522
Author(s):  
Mi-Jin Jeong ◽  
Soyeon Jeon ◽  
Hak-Sun Yu ◽  
Wan-Seob Cho ◽  
Seungho Lee ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Nickel Oxide ◽  
Inflammatory Responses ◽  
Control Group ◽  
Oxide Nanoparticles ◽  
Microbial Composition ◽  
Nickel Oxide Nanoparticles ◽  
Lung Microbiome ◽  
Rat Lungs ◽  
Nio Nps

Nickel oxide nanoparticles (NiO NPs) are highly redox active nanoparticles. They can cause acute and chronic inflammation in rat lungs. Unlike the gut microbiome, the association between the lung microbiome’s role and pulmonary inflammatory response to inhaled nanoparticles remains largely unexplored. We aimed to explore the interaction between the lung microbiome and inflammatory responses in rats exposed to NiO NPs. Thirty female Wistar rats were randomly categorized into control and low- (50 cm2/rat), and high- (150 cm2/rat) dose NiO NPs exposure groups. NiO NPs were intratracheally instilled, and cytological, biochemical, proinflammatory cytokine, and lung microbiome analyses of bronchoalveolar lavage fluid were performed at 1 day and 4 weeks after instillation. NiO NPs caused a neutrophilic and lymphocytic inflammatory response in rat lung. We demonstrated that exposure to NiO NPs can alter the lung microbial composition in rats. In particular, we found that more Burkholderiales are present in the NiO NPs exposure groups than in the control group at 1 day after instillation. Dysbiosis in the lung microbiome is thought to be associated with acute lung inflammation. We also suggested that Burkholderiales may be a key biomarker associated with lung neutrophilic inflammation after NiO NPs exposure.

Protective effect of glycine on renal injury induced by ischemia-reperfusion in vivo

2002 ◽  
Vol 282 (3) ◽  
pp. F417-F423 ◽  
Author(s):  
Ming Yin ◽  
Zhi Zhong ◽  
Henry D. Connor ◽  
Hartwig Bunzendahl ◽  
William F. Finn ◽  
...  
Keyword(s):  
Renal Injury ◽  
Cell Injury ◽  
Ischemia Reperfusion Injury ◽  
Interstitial Fibrosis ◽  
Ischemia Reperfusion ◽  
Control Group ◽  
Renal Tubular Cell ◽  
Sprague Dawley

Although glycine prevents renal tubular cell injury in vitro, its effect in vivo is not clear. The purpose of this study was to investigate whether a bolus injection of glycine given before reperfusion plus continuous dietary supplementation afterward would reduce renal injury caused by ischemia-reperfusion. Female Sprague-Dawley rats received a semisynthetic powdered diet containing 5% glycine and 15% casein (glycine group) or 20% casein (control group). Two days later, renal ischemia was produced by cross-clamping the left renal vessels for 15 min, followed by reperfusion. The right kidney was removed before reperfusion. The postischemic glomerular filtration rate (GFR) showed that renal function was less impaired and recovered more quickly in rats receiving glycine. For example, at day 7, GFR in controls (0.31 ± 0.03 ml · min−1 · 100 g−1) was about one-half that of glycine-treated rats (0.61 ± 0.06 ml · min−1 · 100 g−1, P < 0.05). Furthermore, tubular injury and cast formation observed in controls was minimized by glycine (pathology score, 3.2 ± 0.4 vs. 1.0 ± 0.4, P < 0.05). Urinary lactate dehydrogenase (LDH) concentration was elevated by ischemia-reperfusion in the control group (260 ± 22 U/l), but values were significantly lower by about fourfold (60 ± 30 U/l) in glycine-fed rats. Similarly, free radical production in urine was significantly lower in glycine-treated animals. Importantly, on postischemic day 1, binding of pimonidazole, an in vivo hypoxia marker, was increased in the outer medulla in controls; however, this phenomenon was prevented by glycine. Two weeks later, mild leukocyte infiltration and interstitial fibrosis were still observed in controls, but not in kidneys from glycine-treated rats. In conclusion, these results indicate that administration of glycine indeed reduces mild ischemia-reperfusion injury in the kidney in vivo, in part by decreasing initial damage and preventing chronic hypoxia.

scholarly journals Chitosan Oligosaccharides Protect Sprague Dawley Rats from Cyclic Heat Stress by Attenuation of Oxidative and Inflammation Stress

Animals ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 1074 ◽  
Author(s):  
Ruixia Lan ◽  
Siqi Li ◽  
Qingqing Chang ◽  
Zhihui Zhao
Keyword(s):  
Heat Stress ◽  
Inflammatory Response ◽  
Average Daily Gain ◽  
Relative Weight ◽  
Basal Diet ◽  
Male Rats ◽  
Control Group ◽  
Sprague Dawley ◽  
Chitosan Oligosaccharides ◽  
Cyclic Heat

Chitosan oligosaccharides (COS) exhibits antioxidant and anti-inflammatory properties. The aim of this study was to evaluate the effects of COS on antioxidant system and inflammatory response in heat-stressed rats. A total of 30 male rats were randomly divided to three groups and reared at either 24 °C or 35 °C for 4 h/d for this 7-day experiment: CON, control group with basal diet; HS, heat stress group with basal diet; HSC, heat stress with 200mg/kg COS supplementation. Compared with the CON group, HS significantly decreased (p < 0.05) average daily gain (ADG); average daily feed intake (ADFI); the relative weight of spleen and kidney; the level of liver CAT, GSH-Px, T-AOC, and IL-10; spleen SOD, GSH-Px, GSH, and IL-10; and kidney SOD, GSH-Px, T-AOC, and IL-10, while significantly increased the MDA concentration in liver, spleen, and kidney; the liver IL-1β concentration; and spleen and kidney IL-6 and TNF-α concentration. In addition, dietary COS supplementation significantly improved (p < 0.05) ADG; the relative weight of spleen and kidney; the level of liver GSH-Px, spleen GSH-Px, GSH, and IL-10; and kidney GSH-Px, while significantly decreased (p < 0.05) liver IL-1β concentration under heat stress condition. Collectively, COS was beneficial to heat-stressed rats by alleviating oxidative damage and inflammatory response.

scholarly journals Analysis of phenolic compounds and immunomodulatory activity of areca nut extract from Aceh, Indonesia, against Staphylococcus aureus infection in Sprague-Dawley rats

2020 ◽  
Vol 13 (1) ◽  
pp. 134-140
Author(s):  
Liza Meutia Sari ◽  
Rachmi Fanani Hakim ◽  
Zaki Mubarak ◽  
Andriyanto Andriyanto
Keyword(s):  
Staphylococcus Aureus ◽  
Blood Cells ◽  
White Blood Cells ◽  
Control Group ◽  
Immunomodulatory Activity ◽  
Areca Nut ◽  
Sprague Dawley ◽  
Phytochemical Content ◽  
Sprague Dawley Rats ◽  
Serum Glutamate

Aim: The aim of the study was to investigate the immunomodulatory activity of areca nut extract. The phytochemical content and phenolic composition of the extract were also determined. Materials and Methods: An extract of areca nut was prepared using 96% ethanol and subsequently screened for phytochemical content using a high-performance liquid chromatography (HPLC) method. The immunomodulatory activity of the extract was tested in 35 Sprague-Dawley rats, divided into four groups: One control group and three experimental groups in which the rats received 500, 1000, or 1500 mg/kg of oral areca nut extract biweekly (BW). The extract was orally administered 14 days before the intraperitoneal challenge with Staphylococcus aureus (1×108 CFU/mL). On the 14th day of the experiment, rats in all the four groups were sacrificed. Measurement of the levels of red blood cells, hematocrit (Hct), hemoglobin (Hb), white blood cells (WBCs), lymphocytes, monocytes, neutrophils, basophils, eosinophil, and macrophages were recorded. The activities of serum glutamate oxalate transaminase, serum glutamate pyruvate transaminase, urea, and creatinine were also determined. Results: Areca nut was found to contain an alkaloid, tannin, and flavonoid compounds. HPLC analysis revealed the presence of catechin as the major compound along with quercetin. Administration of areca nut extract in rats infected with S. aureus produced a significant increase in the concentration of WBC but did not affect Hct, Hb, and other cell types. Among the different doses tested, 1000 mg/kg BW was found to be most effective in cellular immunity models. No harmful effects on the liver and kidney functions were observed. Conclusion: The antioxidant activity of areca nut might be attributed to the presence of catechin and quercetin. Administration of areca nut extract increased the number of WBCs and improved the activity and capacity of macrophages significantly in rats infected with S. aureus.

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