Neuropeptide W Attenuates Oxidative Multi-Organ Injury in Rats Induced with Intra-Abdominal Sepsis

Abstract Sepsis leads to systemic hypotension, disturbed perfusion, inflammation and tissue toxicity in vital organs. Neuropeptide W (NPW) has modulatory effects in the control of blood pressure and inflammatory processes, implicating a potential beneficial effect against sepsis-induced oxidative damage. Under anesthesia, male Sprague Dawley rats underwent cecal ligation and puncture. Immediately after surgery, either saline or TNF-alpha inhibitor (etanercept; 1 mg/kg) antibiotic (ceftriaxon; 100 mg/kg) combination or NPW (0.1, 1 or 3 µg/kg) was given subcutaneously, and injections were repeated at 12th and 24th h. The sham-operated control group was treated with saline at the same time points. All rats were euthanized at the 25th h of surgery. Sepsis resulted in oxidative damage of the brain, heart, lung, liver and kidney. Elevations in blood urea nitrogen and alkaline phosphatase, showing renal and hepatic dysfunction, were not evident when septic rats were treated with NPW. NPW reduced serum levels of C-reactive protein, corticosterone and interleukin-6, while histopathologically verified tissue damage in all the studied tissues was ameliorated. NPW treatment suppressed lipid peroxidation in the heart, lung and brain, and the depleted antioxidant GSH levels of the brain and heart were replenished by NPW. Moreover, sepsis-related neutrophil recruitment to liver and lung was also suppressed by NPW. Although survival rate of the rats was not significantly prolonged by NPW, most of these improvements in systemic and local inflammatory events were comparable with those reached by the etanercept and antibiotic combination, suggesting the therapeutic impact of NPW during the acute period of sepsis.

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Systemic Effects Induced by Hyperoxia in a Preclinical Model of Intra-abdominal Sepsis

Mediators of Inflammation ◽

10.1155/2020/5101834 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

M. Isabel García-Laorden ◽

Raquel Rodríguez-González ◽

José L. Martín-Barrasa ◽

Sonia García-Hernández ◽

Ángela Ramos-Nuez ◽

...

Keyword(s):

Cecal Ligation ◽

Experimental Period ◽

Serum Levels ◽

Organ Damage ◽

Abdominal Sepsis ◽

High Oxygen ◽

Continuous Treatment ◽

Preclinical Model ◽

Sprague Dawley ◽

Oxygen Concentrations

Supplemental oxygen is a supportive treatment in patients with sepsis to balance tissue oxygen delivery and demand in the tissues. However, hyperoxia may induce some pathological effects. We sought to assess organ damage associated with hyperoxia and its correlation with the production of reactive oxygen species (ROS) in a preclinical model of intra-abdominal sepsis. For this purpose, sepsis was induced in male, Sprague-Dawley rats by cecal ligation and puncture (CLP). We randomly assigned experimental animals to three groups: control (healthy animals), septic (CLP), and sham-septic (surgical intervention without CLP). At 18 h after CLP, septic ( n = 39 ), sham-septic ( n = 16 ), and healthy ( n = 24 ) animals were placed within a sealed Plexiglas cage and randomly distributed into four groups for continuous treatment with 21%, 40%, 60%, or 100% oxygen for 24 h. At the end of the experimental period, we evaluated serum levels of cytokines, organ damage biomarkers, histological examination of brain and lung tissue, and ROS production in each surviving animal. We found that high oxygen concentrations increased IL-6 and biomarkers of organ damage levels in septic animals, although no relevant histopathological lung or brain damage was observed. Healthy rats had an increase in IL-6 and aspartate aminotransferase at high oxygen concentration. IL-6 levels, but not ROS levels, are correlated with markers of organ damage. In our study, the use of high oxygen concentrations in a clinically relevant model of intra-abdominal sepsis was associated with enhanced inflammation and organ damage. These findings were unrelated to ROS release into circulation. Hyperoxia could exacerbate sepsis-induced inflammation, and it could be by itself detrimental. Our study highlights the need of developing safer thresholds for oxygen therapy.

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Dietary supplementation with housefly (Musca domestica) maggot meal in growing beagles: hematology, serum biochemistry, immune responses and oxidative damage

Annals of Animal Science ◽

10.2478/aoas-2020-0045 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Yang Hong ◽

Jing Zhou ◽

Ming-Ming Yuan ◽

Han Dong ◽

Guo-Qiang Cheng ◽

...

Keyword(s):

Immune Responses ◽

Oxidative Damage ◽

Musca Domestica ◽

Control Diet ◽

Serum Antibody ◽

Serum Levels ◽

Serum Biochemistry ◽

Protein Carbonyl ◽

Control Group ◽

Reactive Protein

AbstractThe present study was carried out to evaluate the hematology, serum biochemistry, immune responses and oxidative damage of growing beagles fed a diet supplemented with housefly (Musca domestica) maggot meal (MM). Weaning beagles (initial body weight 2.69 ± 0.17 kg) were fed a control diet (0% MM) or experimental diet (5% MM) for 42 days. The results indicated that the diet supplemented with 5% MM had no significant effects on the hematology and serum biochemistry of growing beagles (P>0.05). Meanwhile, neither the serum concentrations of lysozyme and C-reactive protein nor the serum antibody responses to canine distemper virus and canine parvovirus were influenced by dietary MM supplementation (P >0.05). However, dogs in the experimental group had lower serum levels of malondialdehyde and protein carbonyl than those in the control group (P<0.05). These findings demonstrated that MM could be used as an alternative protein source in growing beagles without any adverse effects on hematology, serum biochemistry and immune responses. Furthermore, dietary MM could alleviate oxidative damage in growing beagles.

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EFFECT OF PNEUMOPERITONEUM IN MODEL OF ABDOMINAL SEPSIS

JOURNAL OF SURGICAL AND CLINICAL RESEARCH ◽

10.20398/jscr.v11i1.20837 ◽

2020 ◽

Vol 11 (1) ◽

pp. 31-38

Author(s):

Cybelle Dutra Silva ◽

Evelynne Mayara Araújo Silva ◽

Vítor Brasil Medeiros ◽

Aldo Cunha Medeiros

Keyword(s):

Cecal Ligation ◽

Serum Levels ◽

Abdominal Sepsis ◽

Sepsis Group ◽

C Reactive Protein ◽

Serum Cytokine ◽

Reactive Protein ◽

Cytokine Levels ◽

Group 2 ◽

Group 1

ABSTRACT Purpose: This study aims to examine the effects of CO2 pneumoperitoneum on the level of inflammation biomarkers in a model of abdominal sepsis in rats. Methods: Twelve Wistar rats were randomly assigned to two groups of 6 rats each. Under anesthesia, abdominal sepsis was induced by cecal ligation and puncture (CLP). Rats were observed for 24 hours. Group 1: sepsis; group 2: sepsis + pneumoperitoneum with CO2 for 30 min. Six hours after pneumoperitoneum deflation, blood samples were collected by cardiac puncture to measure (TNFα), interleukin-1β (IL-1β), interleukin-6 (IL-6), C-reactive protein (PCR) and procalcitonin (PCT). Statistical analysis using Student t test (p<0.05). Results: All animals survived. The rats with sepsis + pneumoperitoneum had levels of TNFα, IL-1β and IL-6 (542.4 ± 21pg / mL; 312.1 ± 12 pg / mL and 115.4 ± 11 pg / mL (respectively ), significantly lower than in the sepsis group (p = 0.01). Serum cytokine levels in the sepsis group were TNFα = 733.2 ± 24pg / mL; IL-1β = 432.1 ± 15 pg / mL and IL-6 = 232.3 ± 16 pg / mL. Serum levels of PCT and CRP were significantly lower in the sepsis + pneumoperitoneum group than in the sepsis group. (p=0.01). Conclusion: In conclusion, pneumoperitoneum CO2 attenuates the biomarkers of the acute phase inflammatory response associated with perioperative sepsis by PLC.

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Quantitative Analysis of Diffusion Tensor Imaging in Chronic Hepatitis in Rats

10.21203/rs.3.rs-20509/v1 ◽

2020 ◽

Author(s):

Mengping Huang ◽

Xin Lu ◽

Xiaofeng Wang ◽

Jian Shu

Keyword(s):

Chronic Hepatitis ◽

Diffusion Tensor Imaging ◽

Liver Fibrosis ◽

Diffusion Tensor ◽

Control Group ◽

Sprague Dawley ◽

Subcutaneous Injections ◽

Sprague Dawley Rats ◽

Pathological Stages ◽

The Brain

Abstract Background Diffusion tensor imaging (DTI) is mainly used for detecting white matter fiber in the brain. From this, DTI has been applied to assess fiber in liver disorders by prior studies. But non-sufficient data has been obtained if DTI could be used for exactly staging chronic hepatitis. This study is to assess the value of DTI for staging of liver fibrosis (F), necroinflammatory activity (A), and steatosis (S) of chronic hepatitis in rats. Methods Seventy male Sprague-Dawley rats were divided into control group(n = 10) and experimental group(n = 60). The rat models of chronic hepatitis were established by abdominal subcutaneous injections of 40% CCl4. All rats underwent 3.0T MRI. ROIs were placed on DTI to estimate MR parameters (rADC value and FA value). Histopathology was the reference standard. Multiple linear regression was used to analyze the association between MR parameters and pathology. The differences in rADC value and FA value among pathological stages were evaluated by MANOVA or ANOVA. LSD was used to test the differences between each two groups. ROC analysis was performed. Results The numbers of each pathology were as follows: F0(n = 15), F1(n = 11), F2(n = 6), F3(n = 9), F4(n = 6); A0(n = 8), A1(n = 16), A2(n = 16), A3(n = 7); S0(n = 10), S1(n = 7), S2(n = 3), S3(n = 11), S4(n = 16). The rADC value had a negative correlation with liver fibrosis (r=-0.392, P = 0.008) and inflammation (r=-0.359, P = 0.015). FA value had a positive correlation with fibrosis (r = 0.409, P = 0.005). Significant differences were found in FA value between F4 and F0 ~ F3 (P = 0.03), while no significant differences among F0 ~ F3 were found (P > 0.05). AUC of FA value in differentiating F4 from F0 ~ F3 was 0.909(p < 0.001) with 83.3% Sensitivity, 85.4% specificity when the FA value was at the cut-off of 588.089(× 10− 6mm2/s). Conclusion FA value for DTI can distinguish early cirrhosis from normal, mild and moderate liver fibrosis.

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Calcemia and Inflammatory Markers in Early-Onset Neonatal Infection

Acta Medica (Hradec Kralove Czech Republic) ◽

10.14712/18059694.2019.47 ◽

2019 ◽

Vol 62 (2) ◽

pp. 58-61

Author(s):

Štěpán Kutílek ◽

Martina Vracovská ◽

Kamila Pečenková ◽

Hana Brožíková ◽

Richard Pikner ◽

...

Keyword(s):

Early Onset ◽

Inverse Correlation ◽

Protein S ◽

Neonatal Infection ◽

Serum Levels ◽

Control Group ◽

Term Neonates ◽

Reactive Protein ◽

Laboratory Markers ◽

Weak Negative Correlation

Introduction: Ionised hypocalcemia (S-Ca2+) has been repeatedly observed in neonates with sepsis. Our aim was to evaluate total calcemia (S-Ca) and its relationship to laboratory markers of infection. Methods: We retrospectively evaluated total calcemia (S-Ca) and its relationship to laboratory markers of sepsis/infection (serum levels of C-reactive protein – S-CRP and procalcitonin – S-PCT) in 29 full-term neonates with early-onset neonatal infection hospitalized at our neonatology ward between 2012 and 2016. The control group consisted of 705 neonates without infection. Results: In neonates with early-onset infection , the S-Ca on day 1, 2 and 3 was significantly lower (p < 0.0001; p < 0.0001; p = 0.05 versus controls) same as the pooled S-Ca (p < 0.0001 versus controls). There was a weak negative correlation between pooled S-Ca and S-PCT, or pooled S-Ca and S-CRP (r = −0.22, p = 0.06; r = −0.19, p = 0.09). Conclusion: S-Ca was decreased in neonates with early-onset infection and did show a slight tendency to inverse correlation with S-CRP and S-PCT. Pediatricians must be aware of the fact that a drop in total S-Ca should alert their attention to the risk of neonatal infection, and, likewise, that the children with neonatal infection are at a higher risk of hypocalcemia with all its consequences.

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Is Systemic Inflammation Associated With Elevated PSA Serum Levels In Patients Submitted Chronic Hemodialysis?

International Archives of Medicine ◽

10.3823/2522 ◽

2017 ◽

Vol 10 ◽

Author(s):

Gilmar Pereira Silva ◽

Vitor Pereira Xavier Grangeiro

Keyword(s):

Systemic Inflammation ◽

Serum Levels ◽

Chronic Hemodialysis ◽

Control Group ◽

Inclusion Criteria ◽

Reactive Protein ◽

Free Psa ◽

Significant Difference ◽

Level Elevation ◽

Hs Crp

Backgroundː whereas that systemic inflammation (SI) affects 40–60% of patients on hemodialysis (HD) is characterized by serum C-reactive protein (CRP) level elevation or proinflammatory interleukin production or both. We evaluated the association between SI and total (tPSA) and free PSA (fPSA) in patients on HD with tPSA <4ng / ml. Methodsː Sixty patients with chronic kidney disease (CKD) undergoing HD and 20 controls were included. Inclusion criteria were patients aged 18-60 years; tPSA < 4 ng/mL without clinically detectable prostate cancer; and patients undergoing HD for >6 months. Patients were excluded if they had local infections or SI. Hs-CRP was measured using turbidimetry, and tPSA and fPSA levels using immunochemoluminescence. Overall, 27 patients had inflammation (hs-CRP >5 mg/L) and 33 had no inflammation (hs-CRP was ≤5 mg/L). In the control group, hs-CRP was ≤ 1 mg/L. Resultsː there was no significant difference in mean levels among groups 3 and 4 for age (p=0,058), tPSA (p=0,74) and fPSA (p=0,30). The SI did not promote differences between groups 1, 2 and 4 for the levels of tPSA (0,71 ± 0,18 vs 0,67 ± 0,15 vs 0,67 ± 0,11; p=0,69) and fPSA (0,34 ± 0,01 vs 0,34 ± 0,01 vs 0,35 ± 0,01, p= 0,59) . As well as maintained no correlation with tPSA and fPSA (p>0,05). Conclusionː The systemic inflammation in hemodialytic patients without clinically detectable cancer (PSA<4ng/ml) is no associated with changes fractions of tPSA and fPSA.

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Arum conophalloides Aqueous Extract Induced Hepatotoxicity in Rat; Histopathological, Biochemical, and mir-122 Assessments

MicroRNA ◽

10.2174/2211536608666191016142400 ◽

2020 ◽

Vol 9 (3) ◽

pp. 224-231

Author(s):

Amin Derakhshanfar ◽

Javad Moayedi ◽

Mahjoob Vahedi ◽

Abouzar Valizadeh

Keyword(s):

Aqueous Extract ◽

Fold Increase ◽

Normal Structure ◽

Serum Levels ◽

Sprague Dawley ◽

Hydroalcoholic Extract ◽

Sprague Dawley Rats ◽

Liver And Kidney ◽

Biochemical Indices ◽

Potential Hepatotoxicity

Background: Arum conophalloides (A. conophalloides) is a wild edible delicate plant, widely used in traditional medicine. Objective: This study aimed to examine the effects of A. conophalloides extracts on biochemical, molecular, and histopathological changes in the rat. Methods: Fifty adult male Sprague-Dawley rats were divided into 5 groups (10 each) as follows: G1 or control, received distilled water; G2 and G3, treated with the aqueous extract at doses of 200 and 400 mg/kg; G4 and G5, treated with the hydroalcoholic extract at doses of 200 and 400 mg/kg. Prior to and at the end of the experiments, the serum levels of biochemistry parameters and the relative expression of miR-122 were assessed. Moreover, the liver and kidney tissues were examined microscopically. Results: Liver and kidney tissues showed normal structure in all groups. There were no significant changes in biochemical indices or the expression of miR-122 in the extract-treated groups at the dose of 200 mg/kg. However, the group that received the aqueous extract at the dose of 400 mg/kg exhibited a significantly lower level of HDL, LDL, ALT, and ALP in comparison to the control. Additionally, miR-122 expression in this group exhibited a 10-fold increase (P=0.009). Conclusion: The serum level of hepatocyte-specific miR-122 will be more helpful in detecting hepatic changes in early stages than ALT and AST activity or histopathological evaluations of liver sections. Our findings highlight the potential hepatotoxicity of A. conophalloides aqueous extract in a rat model.

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Antioxidant and Hepatoprotective Activity of a New Tablets Formulation fromTamarindus indicaL.

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2016/3918219 ◽

2016 ◽

Vol 2016 ◽

pp. 1-7 ◽

Cited By ~ 7

Author(s):

Jesús Rafael Rodriguez Amado ◽

Ariadna Lafourcade Prada ◽

Julio Cesar Escalona Arranz ◽

Renato Pérez Rosés ◽

Humberto Morris Quevedo ◽

...

Keyword(s):

Lipid Peroxidation ◽

Serum Levels ◽

Hepatoprotective Activity ◽

Negative Control ◽

Diet Group ◽

Control Group ◽

Standard Diet ◽

Tamarindus Indica ◽

Sprague Dawley ◽

Group I

Hepatotoxic chemicals damage liver cells primarily by producing reactive oxygen species. The decoction of the leaves ofTamarindus indicaL. is used for liver disorders. In this work we evaluated the hepatoprotective activity of a tablet formulation of this plant. Thirty-five Sprague Dawley rats were randomly divided into five groups (n=7). First group (I) is control group, fed with standard diet. Groups II to V (hepatotoxic groups) were subjected to a subcutaneous injection of CCl4(0.5 mL/kg). Group II was negative control, fed with standard diet; group III was subjected to administration of Silymarin 150 mg/kg and groups IV and V were treated with tablets in dose of 100 mg/kg and 200 mg/kg, respectively. Lipid peroxidation and the activity of superoxide dismutase, catalase, and reduced glutathione were evaluated. Serum levels of alanine aminotransferase, aspartate aminotransferase, gamma-glutamine transferase, alkaline phosphatase, and a lipid profile were evaluated too. The tablets inhibit lipid peroxidation. The redox balance (SOD-CAT-GSH) remains normal in the experimental groups treated with tablets. The liver function using dose of 200 mg/kg of tablets was better than the other experimental groups. These results justify, scientifically, the ethnobotanical use of the leaves ofTamarindus indicaL.

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Ameliorative Effect of Vernonia amygdalina Plant Extract on Heavy Metal-Induced Liver and Kidney Dysfunction in Rats

Advances in Pharmacological and Pharmaceutical Sciences ◽

10.1155/2020/2976905 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Precious Barnes ◽

Joshua Kwame Yeboah ◽

Wilson Gbedema ◽

Roland Osei Saahene ◽

Benjamin Amoani

Keyword(s):

Heavy Metal ◽

Metal Toxicity ◽

Antioxidant Properties ◽

Ethanolic Extract ◽

Heavy Metal Toxicity ◽

Control Group ◽

Sprague Dawley ◽

Vernonia Amygdalina ◽

Kidney Dysfunction ◽

Liver And Kidney

Heavy metal toxicity contributes to liver and kidney dysfunction and damage through oxidative stress mechanisms; however, from previous studies, extracts from the Vernonia amygdalina plant have shown to possess potent antioxidant properties. This study was aimed at uncovering the potential ameliorative effects of ethanolic extract from Vernonia amygdalina plant in heavy metal toxicity-induced liver and kidney dysfunction. For this study, 44 Sprague Dawley rats were divided into three groups. The control group received a basal diet and water only while the treatment groups received varied dosages of the heavy metals. The copper (Cu) and lead (Pb) groups had five subgroups. The Cu only and Cu recovery subgroups were administered with 16 mg/kg Cu intraperitoneally daily for 14 days, whereas the Pb only and Pb recovery subgroups were administered with 13 mg/kg Pb intraperitoneally daily for 14 days. Subsequently, the Pb only and Cu only subgroups were sacrificed. The three Pb and Cu treatment subgroups received oral graded doses (100 mg/kg, 200 mg/kg, and 300 mg/kg) of the extract for 21 days. The Cu recovery and Pb recovery subgroups were left to recover for 21 days. After histological examinations, the Pb and Cu pretreatment groups showed evidence of focal necrosis accompanied by inflammatory cell infiltrations. The serum levels of liver biomarkers AST, ALT, and GGT, as well as urea and creatinine, were significantly elevated (P=0.01) following copper and lead exposure. Upon posttreatment of the rats with the extract, the physiological levels of the biomarkers were restored and tissue architecture of the organs improved. Thus, the ethanolic extract of Vernonia amygdalina is capable of ameliorating the effects of heavy metal toxicity through potent antioxidative mechanisms.

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Does Oral Ingestion ofPiper sarmentosumCause Toxicity in Experimental Animals?

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/705950 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 4

Author(s):

Maizura Mohd Zainudin ◽

Zaiton Zakaria ◽

Nor Anita Megat Mohd Nordin ◽

Faizah Othman

Keyword(s):

Safety Information ◽

The Body ◽

Control Group ◽

Sprague Dawley ◽

Internal Organs ◽

Haematological Profile ◽

Daily Dose ◽

Liver And Kidney ◽

Prevalence Of Diabetes Mellitus ◽

Herbal Plant

The prevalence of diabetes mellitus has reached epidemic proportion in Malaysia and worldwide. Scientific studies have shown that herbal plantPiper sarmentosumexhibits an antidiabetic property. Despite the extensive usage and studies of this herb as alternative medicine, there is paucity of the literature on the safety information of this plant. Thus, the present study aimed to observe the subacute toxic effects ofPiper sarmentosumaqueous extract (PSAE) on the haematological profile, liver, and kidney in rats. The extract was administered by oral gavage to 6 male and femaleSprague Dawleyrats in daily dose of 50 mg/kg, 300 mg/kg, and 2000 mg/kg for 28 consecutive days. The control group received normal saline. General behavior of the rats, adverse effects, and mortality were observed for 28 days. The haematological and biochemical parameters were determined at baseline and after the treatment. PSAE did not show abnormality on the body weight and gross observation of internal organs. The haematological, biochemical and histopathological profiles showed minimal changes and variation within normal clinical range except for significant increase in serum potassium level that suggests the need of regular monitoring. Nevertheless, these findings suggested that PSAE up to 2000 mg/kg/day did not show subacute toxicity inSprague Dawleyrats.

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