Propylthiouracil-induced hypothyroidism protects ionizing radiation-induced multiple organ damage in rats

The objective of this study was to examine the potential radioprotective properties of propylthiouracil (PTU)-induced hypothyroidism against oxidative organ damage induced by irradiation. Sprague–Dawley rats were pre-treated with saline or PTU (10 mg/kg i.p.) for 15 days, and were then exposed to whole-body irradiation (800 cGy). A group of rats were decapitated at 6 h after exposure to irradiation, while another group was followed for 72 h after irradiation, during which saline or PTU injections were repeated once daily. Lung, liver, kidney and ileum samples were obtained for the determination of malondialdehyde (MDA; an index of lipid peroxidation) and glutathione (GSH, an antioxidant) levels, myeloperoxidase activity (MPO; an index of tissue neutrophil accumulation) and collagen contents, while oxidant-induced DNA fragmentation was evaluated in the ileal tissues. All tissues were also examined microscopically and assayed for the production of reactive oxidants using chemiluminescence (CL). Lactate dehydrogenase (LDH), an indicator of tissue damage, and tumour necrosis factor-α (TNFα) were assayed in serum samples. Irradiation caused a significant decrease in GSH level, which was accompanied by significant increases in MDA levels, MPO activity, CL levels and collagen content of the tissues studied (P<0.05–0.001). Similarly, serum TNFα and LDH were elevated in the irradiated rats as compared with the control group. On the other hand, PTU treatment reversed all these biochemical indices, as well as histopathological alterations induced by irradiation. Our results suggested that PTU-induced hypothyroidism reduces oxidative damage in the lung, hepatic, renal and ileal tissues probably due to hypometabolism, which is associated with decreased production of reactive oxygen metabolites and enhancement of antioxidant mechanisms.

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Discovery of Serum Proteomic Biomarkers for Prediction of Response to Moxibustion Treatment in Rats with Collagen-Induced Arthritis: An Exploratory Analysis

Acupuncture in Medicine ◽

10.1136/acupmed-2015-010909 ◽

2016 ◽

Vol 34 (3) ◽

pp. 184-193 ◽

Cited By ~ 10

Author(s):

Xiao Xu ◽

Miao-Miao Wang ◽

Zhi-ling Sun ◽

Dan-ping Zhou ◽

Ling Wang ◽

...

Keyword(s):

Rat Model ◽

Multiple Testing ◽

Day Treatment ◽

Expression Patterns ◽

Control Group ◽

Sprague Dawley ◽

Collagen Induced Arthritis ◽

Serum Samples ◽

Beneficial Effects ◽

Bovine Collagen

Objective To examine the possible impact of moxibustion on the serum proteome of the collagen-induced arthritis (CIA) rat model. Materials and Methods Thirty-six male Sprague-Dawley rats were included in this experiment. The CIA animal model was prepared by injection of type II bovine collagen in Freund's adjuvant on the first and seventh day. The 36 rats were randomly divided into two groups: the untreated CIA group (control), and the CIA plus treatment with moxibustion (CIA+moxi) group. Moxibustion was administered daily at ST36 and BL23 for 7, 14 or 21 days (n=12 rats each). Arthritis score was used to assess the severity of arthritis. At the end of each 7 day treatment, blood samples from the control group and the CIA+moxi group were collected. After removal of high abundance proteins from serum samples, two-dimensional gel combined with matrix-assisted laser desorption ionisation time-of-flight MS/MS (MALDI-TOF-MS/MS) techniques were performed to examine serum protein expression patterns of the CIA rat model with and without moxibustion treatment. In addition, the relevant proteins were further analysed with the use of bioinformatics analysis. Results Moxibustion significantly decreased arthritis severity in the rats in the CIA+moxi group, when compared with the rats in the CIA group 35 days after the first immunisation (p=0.001). Seventeen protein spots which changed >1.33 or <0.77 at p<0.05 using Bonferonni correction for multiple testing were found to be common to all three comparisons, and these proteins were used for classification of functions using the Gene Ontology method. Consequently, with the use of the Ingenuity Pathway Analysis, the top canonical pathways and a predicted proteomic network related to the moxibustion effect of CIA were established. Conclusions Using the proteomics technique, we have identified novel candidate proteins that may be involved in the mechanisms of action underlying the beneficial effects of moxibustion in rats with CIA. Our findings suggest that immune responses and metabolic processes may be involved in mediating the effects of moxibustion. Moreover, periodxiredoxin I (PRDX1) and inositol 1,4,5-triphosphate receptor (IP3R) may be potential targets.

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Genistein attenuated gastric inflammation and apoptosis in Helicobacter pylori-induced gastropathy in rats

BMC Gastroenterology ◽

10.1186/s12876-020-01555-x ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Prasong Siriviriyakul ◽

Duangporn Werawatganon ◽

Nisarat Phetnoo ◽

Kanjana Somanawat ◽

Tanittha Chatsuwan ◽

...

Keyword(s):

Helicobacter Pylori ◽

Inflammatory Mediators ◽

Kinase Inhibitor ◽

Specific Protein ◽

Control Group ◽

Sprague Dawley ◽

Serum Samples ◽

Necrosis Factor Alpha ◽

Tunel Reaction ◽

H Pylori

Abstract Background Helicobacter pylori (H. pylori) infection is a major cause of chronic gastritis, peptic ulcer diseases and cancer. Genistein (4′,5,7-trihydroxyisoflavone), a tyrosine-specific-protein kinase inhibitor, has been shown to exert an anti-inflammatory property. The aim of this study was to examine the treatment effects of genistein and its mechanisms in rats with H. pylori infection. Methods Eighteen male Sprague-Dawley rats were divided into three groups (6 rats per group): (1) control group (Con); (2) H. pylori infected group (HP): the rats were inoculated with H. pylori (108− 1010 CFU/mL; 1 mL/rat.) for 3 consecutive days; and (3) HP + genistein group (HP + Gen): the rats were inoculated with H. pylori as above. Then, they were gavaged with genistein (16 mg/kg BW) for 14 days. Gastric tissue was used for the determination of nuclear factor (NF)-κB expression by immunohistochemistry (IHC), degree of apoptosis by the terminal deoxynucleotidyl transferasemediated dUTP nick-end labeling (TUNEL) reaction, and histopathology. Serum samples were used to measure the levels of tumor necrosis factor-alpha (TNF-α) and cytokine-induced neutrophil chemoattractant-1 (CINC-1). Results Rats in the HP group had significantly higher levels of pro-inflammatory mediators, NF-κB expression and apoptotic cells when compared with the Con group, and these markers significantly decreased in HP + Gen group when compared with the HP group. The histopathology of HP group showed moderate gastric inflammation and many HP colonization. Gastric pathology in HP + Gen group demonstrated the attenuation of inflammatory cell infiltration and H. pylori colonization. Conclusion Genistein exerted its gastroprotective effects through the reduction of pro-inflammatory mediators, nuclear receptor NF-κB expression and gastric mucosal apoptosis in rats with H. pylori-induced gastropathy.

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Effects of prenatal x-irradiation on motor performance in the rat

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1961.201.4.703 ◽

1961 ◽

Vol 201 (4) ◽

pp. 703-706 ◽

Cited By ~ 28

Author(s):

Jack Werboff ◽

Irving Goodman ◽

Joan Havlena ◽

Melvin R. Sikov

Keyword(s):

Motor Performance ◽

Motor Impairment ◽

Whole Body ◽

Control Group ◽

Albino Rats ◽

Sprague Dawley ◽

X Irradiation ◽

Motor Strength ◽

Low Levels ◽

Almost All

Gravid albino rats of the Sprague-Dawley strain received either 25, 50, or 100 r whole-body X-radiation on either day 5, 10, 15, or 20 of gestation. Controls were sham-irradiated. Over 500 surviving offspring were evaluated on measures of motor maturation of the upright and righting responses, motor strength, and locomotor learning during the neonatal period. The results indicate that radiation exposure of 100 r on day 15 of gestation retards motor maturation of the upright and righting responses. Almost all of the radiation groups show a decrease in motor strength as compared to the control group with maximum deficits in the groups receiving 50 or 100 r on day 10 or 15 of gestation. On the locomotor learning measure, the results are not consistent, but the group receiving 100 r on day 15 of gestation is maximally affected. These deficits in motor performance are related to observable motor impairment. It is concluded that low levels of radiation received prenatally can have detrimental effects on the development of motor performances in the rat.

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Insidious Cerebral Capillary Trauma from Motor Vehicle-Induced Vibration

Neurophysiology and Rehabilitation ◽

10.33805/2641-8991.103 ◽

2017 ◽

pp. 1-7

Author(s):

Prabhjot Grewal ◽

Samita Goyal ◽

Magdelana Matloub ◽

FengYi Shen ◽

Lin-ling Zhang ◽

...

Keyword(s):

Motor Vehicle ◽

Neuronal Damage ◽

Whole Body Vibration ◽

Cerebral Injury ◽

Whole Body ◽

Control Group ◽

Sprague Dawley ◽

Body Vibration ◽

Human Apolipoprotein ◽

Cerebral Capillary

Cumulative cerebral injury from motor vehicle-induced whole body vibration has not been demonstrated thus far. Our lab has demonstrated isolated cerebral injury from whole body vibration and we believe that repetitive vibration can cause cumulative insults, impairing cerebral function. A simulated motor vehicle-induced whole body vibration study was conducted with fifty-six Sprague-Dawley rats divided into seven groups (N=8): (1) 8-week control group; (2) 8-week vibration group (exposed to whole body vibration at 30 Hz and 0.5g acceleration for 4 hours/day, 5 days/week for 8 weeks); (3) 8-week vibration group with preconditioning human apolipoprotein A-I molecule mimetic (4F); (4) 8-week vibration group with post conditioning 4F peptide; (5) 8-week vibration group with pre and post conditioning 4F peptide; (6) 12-week control group; and (7) 12-week vibration group (exposed to the same vibration, 5 days/week for 12 weeks). At the end point, all rats were evaluated by brain histo-pathological studies. The pathology demonstrated capillary constriction with surrounding edema as well as thickened, uneven and damaged capillary walls. Capillary constriction reduces the oxygen supply to cerebral neurons, leading to neuronal damage. In the 12-week vibration group, each effect was more pronounced as compared to the 8-week vibration group. There was no prominent cerebral capillary damage in the 4F-peptide conditioning groups. This study showed cumulative cerebral injury from motor vehicle-induced whole body vibration and demonstrated the preventative effect of 4F-peptide conditioning.

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Nafamostat Mesilate, a Broad Spectrum Protease Inhibitor, Modulates Platelet, Neutrophil and Contact Activation in Simulated Extracorporeal Circulation

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650224 ◽

1996 ◽

Vol 75 (01) ◽

pp. 076-082 ◽

Cited By ~ 40

Author(s):

Sumuk Sundaram ◽

Nicolas Gikakis ◽

C Erik Hack ◽

Stefan Niewiarowski ◽

L H Edmunds ◽

...

Keyword(s):

Protease Inhibitor ◽

Complement Activation ◽

Postoperative Bleeding ◽

Organ Damage ◽

Multiple Organ ◽

Control Group ◽

Nafamostat Mesilate ◽

C1 Inhibitor ◽

Contact Activation ◽

Induced Aggregation

SummaryActivation of humoral and cellular participants in inflammation enhances the risk of postoperative bleeding and multiple organ damage in cardiopulmonary bypass (CPB). We now compare the effects of heparin alone in combination with nafamostat mesilate (NM), a protease inhibitor with specificity of trypsin-like enzymes, in an extracorporeal circuit which simulates CPB. NM significantly inhibits the release of platelet (β-thromboglobulin (βTG) at 60 and 120 min. Platelet counts do not differ. ADP-induced aggregation decreases in circuits with NM, which is due to a direct effect of NM on platelet function. NM prevents any significant release of neutrophil elastase; at 120 min, plasma elastase-α1antitrypsin complex is 0.16 μg/ml in the NM group and 1.24 μg/ml in the control group. NM completely inhibits formation of complexes of C1 inhibitor with kallikrein and FXIIa. NM does not alter markers of complement activation (C1-C1-inhibitor complex and C5b-9), or indicators of thrombin formation (F1.2). However, at 120 min, thrombin activity as measured by release of fibrinopeptide A is significantly decreased. The data indicate that complement activation during CPB correlates poorly with neutrophil activation and that either kallikrein or FXIIa or both may be more important agonists. The ability of NM to inhibit two important contact system proteins and platelet and neutrophil release raises the possibility of suppressing the inflammatory response during clinical CPB.

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Relationship Between Serum Severe Acute Respiratory Syndrome Coronavirus 2 Nucleic Acid and Organ Damage in Coronavirus 2019 Patients: A Cohort Study

Clinical Infectious Diseases ◽

10.1093/cid/ciaa1085 ◽

2020 ◽

Cited By ~ 2

Author(s):

Dan Xu ◽

Fuling Zhou ◽

Wenbo Sun ◽

Liangjun Chen ◽

Lan Lan ◽

...

Keyword(s):

Nucleic Acid ◽

Severe Acute Respiratory Syndrome ◽

Troponin I ◽

Demographic Data ◽

Organ Damage ◽

Multiple Organ ◽

Serum Samples ◽

Cardiac Damage ◽

Multiple Organs ◽

Laboratory Biomarkers

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide and has the ability to damage multiple organs. However, information on serum SARS-CoV-2 nucleic acid (RNAemia) in patients affected by coronavirus disease 2019 (COVID-19) is limited. Methods Patients who were admitted to Zhongnan Hospital of Wuhan University with laboratory-confirmed COVID-19 were tested for SARS-COV-2 RNA in serum from 28 January 2020 to 9 February 2020. Demographic data, laboratory and radiological findings, comorbidities, and outcomes data were collected and analyzed. Results Eighty-five patients were included in the analysis. The viral load of throat swabs was significantly higher than of serum samples. The highest detection of SARS-CoV-2 RNA in serum samples was between 11 and 15 days after symptom onset. Analysis to compare patients with and without RNAemia provided evidence that computed tomography and some laboratory biomarkers (total protein, blood urea nitrogen, lactate dehydrogenase, hypersensitive troponin I, and D-dimer) were abnormal and that the extent of these abnormalities was generally higher in patients with RNAemia than in patients without RNAemia. Organ damage (respiratory failure, cardiac damage, renal damage, and coagulopathy) was more common in patients with RNAemia than in patients without RNAemia. Patients with vs without RNAemia had shorter durations from serum testing SARS-CoV-2 RNA. The mortality rate was higher among patients with vs without RNAemia. Conclusions In this study, we provide evidence to support that SARS-CoV-2 may have an important role in multiple organ damage. Our evidence suggests that RNAemia has a significant association with higher risk of in-hospital mortality.

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Significance of TNF in hemorrhage-related hemodynamic alterations, organ injury, and mortality in rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1997.272.5.h2219 ◽

1997 ◽

Vol 272 (5) ◽

pp. H2219-H2226 ◽

Cited By ~ 4

Author(s):

S. Bahrami ◽

Y. M. Yao ◽

G. Leichtfried ◽

H. Redl ◽

I. Marzi ◽

...

Keyword(s):

Survival Rate ◽

Hemorrhagic Shock ◽

Peripheral Resistance ◽

Resistance Index ◽

Organ Damage ◽

Multiple Organ ◽

Organ Injury ◽

Tnf Alpha ◽

Control Group ◽

Necrosis Factor Alpha

To evaluate the role of tumor necrosis factor-alpha (TNF-alpha) in hemodynamic alterations, multiple organ damage, and mortality caused by hemorrhagic shock, we employed a monoclonal antibody to TNF-alpha (TNF-alpha MAb) in anesthetized rats subjected to prolonged hemorrhagic shock (mean arterial pressure of 30–x35 mmHg for 180 min) followed by resuscitation over 50 min. Treatment of rats with 20.0 mg/kg TNF-alpha MAb 15 min after the end of resuscitation significantly decreased the total peripheral resistance index (P = 0.031) and provided remarkable protection from multiple organ damage compared with controls. The 48-h survival rate was significantly higher in the treatment group (73.3%) than in the control group (26.7%; P = 0.029). The results suggest that TNF-alpha induced by hemorrhagic shock in rats is an important mediator of pathophysiological alterations associated with cardiovascular abnormalities, multiple organ injury, and even lethality. Postresuscitation treatment with TNF-alpha MAb, even after an initial TNF-alpha formation had occurred, significantly attenuated the cardiovascular consequences and improved the survival rate. Thus monoclonal antibodies to TNF-alpha might provide new prospects in the treatment of hemorrhage-related disorders.

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Can Tumor Necrosis Factor-α and Interleukin-6 Be Used as Prognostic Markers of Infection following Ureteroscopic Lithotripsy?

ISRN Urology ◽

10.1155/2014/457063 ◽

2014 ◽

Vol 2014 ◽

pp. 1-5 ◽

Cited By ~ 3

Author(s):

Athanasios Bantis ◽

Georgios Tsakaldimis ◽

Athanasios Zissimopoulos ◽

Stilianos Giannakopoulos ◽

Christos Kalaitzis ◽

...

Keyword(s):

Prognostic Markers ◽

Surgical Intervention ◽

Infectious Complications ◽

Ureteral Stones ◽

Control Group ◽

Serum Samples ◽

Ureteroscopic Lithotripsy ◽

Postoperative Fever ◽

Factor Α ◽

Necrosis Factor

Introduction. Ureteroscopic lithotripsy (URS) although highly effective for the treatment of ureteral stones is associated with certain complications, the more common of which are postoperative fever and infection. In the present study we aimed to evaluate the levels of serum cytokines in patients undergoing ureteroscopic lithotripsy and investigate any possible correlation between levels of cytokines and infectious complications after URS. Materials and Methods. Thirty patients (19 males, 11 females), with a mean age of 47 (range: 26–68) that underwent URS lithotripsy for ureteral stones, and 10 healthy volunteers serving as the control group were enrolled in this study. Serum samples for TNF-α and IL-6 were obtained before surgical intervention and after 1, 24, and 48 hours and 2 , 24, and 48 hours, respectively. The preoperative and postoperative levels were compared and correlated with the possible complications after URS. Results. Serum TNF-α levels were statistically significant, increased 1 hour (P=0.0083) and 48 hours (P<0.001) after operation. IL-6 levels were found statistically significant, elevated after 2 and 24 hours from the URS (P<0.001). In 2 patients we observed postoperative fever (>38.5°C). These two patients had high preoperative values of TNF-α and IL-6 ( 30 and 50 pg/mL, resp.) and these values increased postoperatively. Conclusion. High preoperative levels of serum TNF-α and IL-6 may indicate a predisposition for postoperative inflammation and infection following URS lithotripsy.

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Human umbilical cord mesenchymal stem cells (hUCMSCs) promotes the regeneration of severe endometrial damage in a rat model

10.21203/rs.2.20062/v1 ◽

2020 ◽

Author(s):

Zhuang Mei ◽

Zhang Wuwen ◽

Liu Dan ◽

Yan Hua ◽

Fang Ge ◽

...

Keyword(s):

Stem Cells ◽

Messenger Rna ◽

Normal Group ◽

Control Group ◽

Human Umbilical Cord ◽

Sprague Dawley ◽

Expression Levels ◽

Paracrine Secretion ◽

Factor Α ◽

Injury Control

Abstract Background: Intrauterine adhesions (IUA) is a common endometrial disease, which is one of the causes of infertility. Transplantation of stem cells may provide a viable solution for endometrial repair and regeneration. We made a model of severe endometrial injury in rats, transplanted hUCMSCs, and studied the effect of hUCMSCs on endometrial regeneration. Methods: Thirty-two female Sprague-Dawley rats were randomly divided into four groups: normal group, injury control group, MSC1 group and MSC2 group. After 15 days of intervention and transplantation, histological analysis was performed and cytokine messenger RNA expression was measured. Results: The HE staining results showed that the endometrial tissue of the injury control group was significantly damaged, and the endometrial tissues of the MSC1 group and the MSC2 group were improved. We did not detect the expression of keratin and vimentin in the injury control group. However, there was the expression of keratin and vimentin in the MSC1 group and the MSC2 group. The results of Real-time PCR showed that the expression levels of tumor necrosis factor-α (TNF-α) mRNA in the normal group and MSC1 group was lower than that of the injury control group (P<0.05).The expression levels of basic fibroblast growth factor (bFGF) mRNA in the normal group and MSC2 group were higher than that of the injury control group (P<0.05). The expression levels of interleukin-1β (IL-1β) mRNA in the normal group was lower than that of the control group (P<0.05). Conclusions: Transplantation of hUCMSCs promoted the recovery of severe endometrial damage in rats. These findings suggest the effect may be related to the mechanisms of homing and paracrine secretion.

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Increase of Angiogenesis and Osteogenesis by Local Application of Simvastatin Depends on VEGF

10.21203/rs.3.rs-69245/v1 ◽

2020 ◽

Author(s):

Jie Tan ◽

Hong Wang ◽

Guohong Du ◽

Huijie Leng ◽

Chunli Song

Keyword(s):

Bone Formation ◽

Western Blot ◽

Dual Energy ◽

Male Rats ◽

Control Group ◽

Sprague Dawley ◽

Micro Computed Tomography ◽

Vegf Expression ◽

Serum Samples ◽

X Ray

Abstract Aims Simvastatin stimulates both BMP-2 and VEGF expression, but it is unknown which is more important for bone formation. This study was undertaken to determine whether these effects could be blocked by the anti-VEGF antibody bevacizumab. Methods 60 Sprague–Dawley male rats were randomly divided into five groups (n = 12 per group): normal control; simvastatin 0 mg or 0.5 mg; and bevacizumab with simvastatin 0 mg or 0.5 mg. Simvastatin groups were administered intraosseous injections of simvastatin delivered by thermosensitive poloxamer. Bevacizumab groups were given bevacizumab intraperitoneally or the same volume of saline. Serum samples were collected before the treatment and every two weeks thereafter. Four weeks after the treatment, four rats randomly selected from each group were subjected to Microfil® perfusion. The remaining eight rats was evaluated with dual energy X-ray absorptiometry (DXA) and micro-computed tomography (µCT). Four specimens (left tibias) were randomly selected from each group for undecalcified histology, the other four specimens selected for Western blot to analyse the changes of expression of BMP-2. Results local injection of simvastatin significantly increased bone formation. Microfil® perfusion showed that there were more vessels both in the bone marrow and around the bone after a single-dose simvastatin injection. Western blot analysis also confirmed that the expression levels of BMP2 were significantly higher in the simvastatin-treated groups compared with the control group. Compared with the simvastatin group, bevacizumab blunted the simvastatin-induced increase in bone mass and angiogenesis. Conclusion The anabolic effect of simvastatin on bone formation is through VEGF-related mechanisms.

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