scholarly journals The Effects of Montelukast on Antioxidant Enzymes and Proinflammatory Cytokines on the Heart, Liver, Lungs, and Kidneys in a Rat Model of Cecal Ligation and Puncture–Induced Sepsis

2011 ◽  
Vol 11 ◽  
pp. 1341-1356 ◽  
Author(s):  
Ali Kagan Coskun ◽  
Murat Yigiter ◽  
Akgun Oral ◽  
Fehmi Odabasoglu ◽  
Zekai Halici ◽  
...  
Keyword(s):  
Tissue Injury ◽  
Cecal Ligation ◽  
Lipid Peroxide ◽  
Multiple Organ ◽  
Control Group ◽  
Myeloperoxidase Activity ◽  
Protective Effects ◽  
Cecal Ligation And Puncture ◽  
Necrosis Factor Alpha ◽  
Liver And Kidney

We investigated the potential protective effects of montelukast (MLK) on cecal ligation and puncture (CLP)–induced tissue injury in vital organs — liver, heart, kidneys, and especially lungs — through inhibition of the proinflammatory cytokine response and the generation of reactive oxygen species (ROS) in rats. The rat groups were (1) a 10-mg/kg MLK-treated CLP group; (2) a 20-mg/kg MLK-treated CLP group; (3) a 20-mg/kg MLK-treated, sham-operated group; (4) a CLP control group; and (5) a sham-operated control group. MLK treatment significantly decreased proinflammatory (tumor necrosis factor-alpha, interleukin-6) cytokine levels following CLP. The lipid peroxide level increased in the lung, heart, liver, and kidney tissues after CLP-induced sepsis, and myeloperoxidase activity increased in the lung, heart, and liver tissues. MLK attenuated this elevation in all tissues except the kidney, dose dependently. The glutathione levels and superoxide dismutase activity were significantly increased in the lung, liver, and kidney tissues after MLK treatment. MLK treatment after CLP also potentially reduced mortality. The lung and kidney tissues were the most protected by MLK under sepsis conditions. We can suggest that MLK reverses the systemic inflammatory reaction to polymicrobial sepsis and thereby reduces multiple organ failure.

Protective effect of febuxostat in sepsis-induced liver and kidney injuries after cecal ligation and puncture with the impact of xanthine oxidase, interleukin 1β, and c-Jun N-terminal kinases

2020 ◽  
Vol 39 (7) ◽  
pp. 906-919 ◽  
Author(s):  
YF Ibrahim ◽  
RR Fadl ◽  
SAE Ibrahim ◽  
MF Gayyed ◽  
AMA Bayoumi ◽  
...  
Keyword(s):  
Protective Effect ◽  
Xanthine Oxidase ◽  
Tissue Injury ◽  
Cecal Ligation ◽  
Elevated Serum ◽  
Albino Rats ◽  
Cecal Ligation And Puncture ◽  
Necrosis Factor Alpha ◽  
Liver And Kidney ◽  
The Impact

Sepsis is one of the most common causes of death among hospitalized patients. Activity of xanthine oxidase (XO), a reactive oxygen species-producing enzyme, is known to be elevated in septic patients. Our aim was to investigate the possible protective role of XO inhibitor, febuxostat (FEB), in a rat model of sepsis-induced liver and kidney injures. Adult male albino rats were divided into four groups ( n = 12 each): sham control, sham + FEB, cecal ligation and puncture (CLP), and CLP + FEB groups. FEB (10 mg/kg per os (p.o.)) was given once daily for 2 days and 30 min prior to laparotomy with CLP. CLP was associated with a high mortality rate accompanied by significant liver and kidney injuries indicated by elevated serum alanine aminotransferase, aspartate aminotransferase, urea, and creatinine levels and confirmed by histopathological tissue injury. Moreover, there was an increase in neutrophil gelatinase-associated lipocalin, uric acid, malondialdehyde, and nitric oxide levels and with decreased superoxide dismutase activity and total antioxidant capacity. In addition, CLP caused increased expression of the inflammatory markers tumor necrosis factor alpha, interleukin 1beta protein levels, and nuclear factor kappa B immunoexpression. Finally, CLP operated rats exhibited an upregulation in the apoptotic mediators, caspase 3, and P-C-Jun N-terminal kinases (JNK) proteins. FEB treatment of CLP rats caused a significant improvement and normalization in all measured parameters. Moreover, FEB amerliorates degenerative histopathological changes and improves the overall survival rate. In conclusion, FEB exhibited a protective effect in sepsis-induced liver and kidney injuries most probably through its anti-inflammatory, antioxidant, and antiapoptotic properties and attenuating JNK signaling pathway secondary to its XO enzyme inhibitory activity.

scholarly journals Evaluation the cardiopulmonary markers in cecal ligation and puncture induced sepsis in Wistar rats

2020 ◽  
Vol 6 (5) ◽  
Author(s):  
Tina Didari ◽  
Shokoufeh Hassani ◽  
Maryam Baeeri ◽  
Vida Kazemi ◽  
Mohammad Abdollahi ◽  
...  
Keyword(s):  
Wistar Rats ◽  
Cecal Ligation ◽  
Myocardial Necrosis ◽  
Control Group ◽  
Sham Operation ◽  
Myeloperoxidase Activity ◽  
Cecal Ligation And Puncture ◽  
Necrosis Factor Alpha ◽  
Needle Size ◽  
Pathological Assessment

Objective: Sepsis is a clinical problem caused by host immune disability against pathogens. Rodent Cecal Ligation and Puncture (CLP) models mimic sepsis in humans. Gauges needle size in CLP is related to cytokine storm, inflammation, and organ failure. This study focus, for the first time, on precise and inexpensive biochemical markers to evaluate the difference of sepsis severity in the heart and lung tissues, one day after cecal ligation and puncture-induced sepsis with needle gauge 18 (G-18). Methods: Twelve adult male Wistar rats were randomly allocated into two groups of 6 animals. These groups include; sham operation as the control group and underwent CLP procedure with G-18. All rats were sacrificed 24 hours after CLP then lungs and heart samples were collected for biochemical and histological assessment. Following the procedure, reactive oxygen species (ROS), Myeloperoxidase Activity (MPO), Tumor Necrosis Factor-Alpha (TNF-α), High Mobility Group Box 1 (HMGB1), lactate generation, caspases (-3 and -9), gene expression of autophagy and cellular hypoxia and pathological assessment of both tissues were measured. Results: Increased level of ROS, MPO, pro-inflammatory cytokines, hyperlactatemia, caspases production, overexpression of hypoxia (PRKAA1 gene), and autophagy (MAP1LC3B gene) in the lungs were higher compared to heart 24 hours after the procedure. Moreover, hyperplasia of pneumocyte and inflammatory cells, and myocardial necrosis were found in the pathological assessment. Conclusion: The purpose of  study was to determine the severity of sepsis by means of cost effective and precise inflammatory markers. Our findings demonstrated that injury-related indicators in lungs meaningfully increased compared to heart 24 hours after CLP.

scholarly journals Parenteral Succinate Reduces Systemic ROS Production in Septic Rats, but It Does Not Reduce Creatinine Levels

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Sebastián P. Chapela ◽  
Isabel Burgos ◽  
Christian Congost ◽  
Romina Canzonieri ◽  
Alexis Muryan ◽  
...  
Keyword(s):  
Complex I ◽  
Electron Transport Chain ◽  
Cecal Ligation ◽  
Multiple Organ ◽  
Sepsis Group ◽  
Control Group ◽  
Ros Production ◽  
Oxygen Species ◽  
Cecal Ligation And Puncture ◽  
Transport Chain

In sepsis, reactive oxygen species (ROS) production is increased. This process takes place mainly within the electron transport chain. ROS production is part of the pathophysiology of multiple organ failure in sepsis. Succinate yields Dihydroflavine-Adenine Dinucleotide (FADH2), which enters the chain through complex II, avoiding complex I, through which electrons are lost. The aim of this work is to determine if parenteral succinate reduces systemic ROS production and improves kidney function. Rats with cecal ligation and puncture were used as model of sepsis, and 4 groups were made: Control group; Succinate group, which only received parenteral succinate; Sepsis group; and Sepsis which received parenteral succinate. Systemic ROS are measured 24 hours after the procedure. Rats subjected to cecal puncture treated with succinate had less systemic ROS than Septic untreated rats (p=0.007), while there were no differences in creatinine levels (p=0.07). There was no correlation between creatinine and systemic ROS levels (p=0.3). We concluded that parenteral succinate reduces ROS levels, but it does not reduce creatinine levels. Since there is no correlation between both levels, the processes would not be related.

scholarly journals Tripterygium glycoside improves regulatory T cells and attenuates acute organ dysfunction in septic mice

2021 ◽  
Vol 19 ◽  
pp. 205873922110008
Author(s):  
Xiaoming Zhang ◽  
Xiaojie Zhou
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Cecal Ligation ◽  
Multiple Organ ◽  
Protective Effects ◽  
Cecal Ligation And Puncture ◽  
Mice Model ◽  
Tnf Α ◽  
Lung And Kidney ◽  
Pro Inflammatory Cytokines

Sepsis is a fatal infectious disease accompanied by multiple organ failure. Immune dysfunction and inflammatory response play an important role in the progression of the disease. Tripterygium glycoside (TG) has immune suppression and anti-inflammatory effects. Here, we investigated the effects of TG on cecal ligation and puncture (CLP)-induced sepsis. Septic mice model was induced by cecal ligation and puncture(CLP), after administration of TG, specimens are collected at designated time points. Histopathology changes of lung tissues and Kidney tissues were observed under light microscope, magnetic microbeads were used to isolate splenic CD4+CD25+ regulatory T cells (Tregs), and phenotypes were then analyzed by flow cytometry. ELISA method was employed to detect the concentrations of plasma TNF-α, IL-6, and IL-10. Nuclear p-NF-κB and Cytoplasmic IkB-a was detected by western blot. TG administration significantly alleviated lung and kidney inflammatory injury and improved the survival of septic mice. Furthermore, the suppressive function of regulatory T cells was enhanced and plasma expression of IL-10 was increased following TG treatment. The NF-B signaling pathway and secretion of plasma TNF-α and IL-6 was notably inhibited in septic mice treated with TG. TG exerts protective effects through improving regulatory T cells and attenuating pro-inflammatory cytokines in septic mice.

Juglone Attenuates Sepsis-Induced Acute Lung Injury via Suppression of the TLR4/Nf-κb Pathway

2020 ◽  
Vol 18 (2) ◽  
pp. 201-206
Author(s):  
Qiu Nan ◽  
Xu Xinmei ◽  
He Yingying ◽  
Fan Chengfen
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Nuclear Factor Kappa B ◽  
Cecal Ligation ◽  
Myeloperoxidase Activity ◽  
Nuclear Factor ◽  
Cecal Ligation And Puncture ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Nuclear Factor Kappa

Sepsis, with high mortality, induces deleterious organ dysfunction and acute lung injury. Natural compounds show protective effect against sepsis-induced acute lung injury. Juglone, a natural naphthoquinone, demonstrates pharmacological actions as a pro-apoptotic substrate in tumor treatment and anti-inflammation substrate in organ injury. In this study, the influence of juglone on sepsis-induced acute lung injury was investigated. First, a septic mice model was established via cecal ligation and puncture, and then verified via histopathological analysis of lung tissues, the wet/dry mass ratio and myeloperoxidase activity was determined. Cecal ligation and puncture could induce acute lung injury in septic mice, as demonstrated by alveolar damage and increase of wet/dry mass ratio and myeloperoxidase activity. However, intragastric administration juglone attenuated cecal ligation and puncture-induced acute lung injury. Secondly, cecal ligation and puncture-induced increase of inflammatory cells in bronchoalveolar lavage fluid was also alleviated by the administration of juglone. Similarly, the protective effect of juglone against cecal ligation and puncture-induced acute lung injury was accompanied by a reduction of pro-inflammatory factor secretion in bronchoalveolar lavage fluid and lung tissues. Cecal ligation and puncture could activate toll-like receptor 4/nuclear factor-kappa B signaling pathway, and administration of juglone suppressed toll-like receptor 4/nuclear factor-kappa B activation. In conclusion, juglone attenuated cecal ligation and puncture-induced lung damage and inflammatory response through inactivation of toll-like receptor 4/nuclear factor-kappa B, suggesting a potential therapeutic strategy in the treatment of sepsis-induced acute lung injury.

Abstract 320: End-Tidal Carbon Dioxide Can Guide Fluid Resuscitation in a Cecal Ligation and Puncture Induced Rat Model of Sepsis

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
Jing Xu ◽  
Guanghui Zheng ◽  
Liangliang Wu ◽  
Xiangshao Fang ◽  
Yue Wang ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Survival Time ◽  
Fluid Resuscitation ◽  
Rat Model ◽  
Cecal Ligation ◽  
Control Group ◽  
Cecal Ligation And Puncture ◽  
End Tidal Carbon Dioxide ◽  
Lactate Levels ◽  
End Tidal

Introduction: Abnormal levels of end-tidal carbon dioxide (ETCO 2 ) may reflect a derangement in perfusion, metabolism, or gas exchange. It is unclear if ETCO 2 can be used for fluid resuscitation (FR) compared with traditional mean arterial pressure (MAP) as an outcome predictor in sepsis. Hypothesis: Use of ETCO2 is better than MAP in guiding fluid resuscitation to improve lactate levels and microcirculatory blood flow in sepsis. Methods: Thirty-five male Sprague-Dawley rats weighing 350-400g were randomized to: 1) SHAM, n=5; 2) cecal ligation and puncture (CLP) Control group (with CLP, without FR, n=10); 3) ETCO 2 group (with CLP, FR began when ETCO 2 ≤25 mmHg, n=10) and 4) MAP group (with CLP, FR began when MAP≤100 mmHg, n=10). Lactate level, cardiac output (CO), perfused small vessel density (PSVD) and sublingual microvascular flow index (MFI) was assessed at baseline, 2 h, 4 h, 8 h, 10 h and 12 h post-CLP. Survival duration was recorded. Results: After FR,CO in the ETCO 2 group increased compared with the MAP group 12h after CLP while lactate levels decreased compared with the Control and MAP groups (p<0.05) (Figure-1). Both sublingual PSVD and MFI decreased after CLP in the control group and MAP group but significantly improved in the ETCO 2 group 8h post-CLP. The average survival time in the ETCO 2 group was significantly greater than MAP group (Figure-2). Conclusions: ETCO 2 guided FR was associated with improved CO, lactate, microcirculatory flow, and survival time compared to MAP guided FR in a CLP-induced rat model of sepsis.

scholarly journals Protective Role of Coenzyme Q10 in Acute Sepsis-Induced Liver Injury in BALB/c Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Qian-wei Li ◽  
Qin Yang ◽  
Hong-Yang Liu ◽  
Yu-ling Wu ◽  
Yu-Hua Hao ◽  
...  
Keyword(s):  
Liver Injury ◽  
Coenzyme Q10 ◽  
Cecal Ligation ◽  
Protective Role ◽  
Hepatic Tissue ◽  
Control Group ◽  
Cecal Ligation And Puncture ◽  
Sequestosome 1

Sepsis increases the risk of the liver injury development. According to the research works, coenzyme Q10 exhibits hepatoprotective properties in vivo as well as in vitro. Current work aimed at investigating the protective impacts of coenzyme Q10 against liver injury in septic BALB/c mice. The male BALB/c mice were randomly segregated into 4 groups: the control group, the coenzyme Q10 treatment group, the puncture and cecal ligation group, and the coenzyme Q10+cecal ligation and puncture group. Cecal ligation and puncture was conducted after gavagaging the mice with coenzyme Q10 during two weeks. Following 48 h postcecal ligation and puncture, we estimated hepatic biochemical parameters and histopathological changes in hepatic tissue. We evaluated the expression of factors associated with autophagy, pyroptosis, and inflammation. Findings indicated that coenzyme Q10 decreased the plasma levels in alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase in the cecal ligation and puncture group. Coenzyme Q10 significantly inhibited the elevation of sequestosome-1, interleukin-1β, oligomerization domain-like receptor 3 and nucleotide-binding, interleukin-6, and tumor necrosis factor-α expression levels; coenzyme Q10 also increased beclin 1 levels. Coenzyme Q10 might be a significant agent in the treatment of liver injury induced by sepsis.

l-theanine alleviates liver and kidney dysfunction in septic rats induced by cecal ligation and puncture

Life Sciences ◽  
2020 ◽  
Vol 249 ◽  
pp. 117502 ◽  
Author(s):  
Meltem Malkoç ◽  
Huriye Patan ◽  
Serap Özer Yaman ◽  
Süleyman Türedi ◽  
Gökçen Kerimoğlu ◽  
...  
Keyword(s):  
Cecal Ligation ◽  
Cecal Ligation And Puncture ◽  
Kidney Dysfunction ◽  
Liver And Kidney

scholarly journals Impact of Coenzyme Q10 Administration on Lead Acetate-Induced Testicular Damage in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Manal El-khadragy ◽  
Wafa A. Al-Megrin ◽  
Norah A. AlSadhan ◽  
Dina M. Metwally ◽  
Rehab E. El-Hennamy ◽  
...  
Keyword(s):  
Coenzyme Q10 ◽  
Lead Acetate ◽  
Interleukin 1 ◽  
Tween 80 ◽  
Control Group ◽  
Protective Effects ◽  
Necrosis Factor Alpha ◽  
Coq10 Supplementation ◽  
Induced Apoptosis ◽  
Testicular Injury

Exposure to lead (Pb) causes multiorgan dysfunction including reproductive impairments. Here, we examined the protective effects of coenzyme Q10 (CoQ10) administration on testicular injury induced by lead acetate (PbAc) exposure in rats. This study employed four experimental groups (n=7) that underwent seven days of treatment as follows: control group intraperitoneally (i.p.) treated with 0.1 ml of 0.9% NaCl containing 1% Tween 80 (v:v), CoQ10 group that was i.p. injected with 10 mg/kg CoQ10, PbAc group that was i.p. treated with PbAc (20 mg/kg), and PbAc+CoQ10 group that was i.p. injected with CoQ10 2 h after PbAc. PbAc injection resulted in increasing residual Pb levels in the testis and reducing testosterone, luteinizing hormone, and follicle-stimulating hormone levels. Additionally, PbAc exposure resulted in significant oxidative damage to the tissues on the testes. PbAc raised the levels of prooxidants (malondialdehyde and nitric oxide) and reduced the amount of endogenous antioxidative proteins (glutathione and its derivative enzymes, catalase, and superoxide dismutase) available in the cell. Moreover, PbAc induced the inflammatory response as evidenced by the upregulation of inflammatory mediators (tumor necrosis factor-alpha and interleukin-1 beta). Further, PbAc treatment induced apoptosis in the testicular cells, as indicated by an increase in Bax and caspase 3 expression, and reduced Bcl2 expression. CoQ10 supplementation improved testicular function by inhibiting Pb accumulation, oxidative stress, inflammation, cell death, and histopathological changes following PbAc exposure. Our findings suggest that CoQ10 can act as a natural therapeutic agent to protect against the reproductive impairments associated with PbAc exposure.

scholarly journals HISTOLOGICAL STUDY ON THE PROTECTIVE EFFECTS OF TAMARIND SEED EXTRACT ON COBRA VENOM IN MICE

2017 ◽  
Vol 10 (10) ◽  
pp. 301
Author(s):  
Imad M Al-ani ◽  
Soraya Ismail ◽  
Khin M Maung ◽  
Pakeer Oothuman ◽  
Sinan Mohammed Abdullah Al-mahmood
Keyword(s):  
Histological Study ◽  
Seed Extract ◽  
Cobra Venom ◽  
Control Group ◽  
Protective Effects ◽  
Histopathological Changes ◽  
Tamarind Seed ◽  
Snake Bites ◽  
Medical Plant ◽  
Liver And Kidney

  Objective: Tamarind (Tamarindus indica) has been used as a medical plant for treating many human and animal diseases and widely used as a traditional herbal medicine for the treatment of snake bites. The objective of the study is to investigate whether tamarind seed extract (TSE) has neutralization activity on an adverse histological reaction against venoms of the King Cobra.Methods: A total of 20 healthy mature male mice were randomly divided into 4 groups with 5 mice in each. The control group was injected with 1 ml of normal saline. The second group was injected subcutaneously with a single dose of 24.96 μg/20 g King Cobra venom (KCV) solution. The third group was injected with the same dose of KCV solution and 10 mg/20 g of TSE. The fourth group was injected with the same dose of KCV solution and 15 mg/20 g TSE solution. The animals were sacrificed after 24 hrs of injection of the solution. Fragments of muscle, kidney, and liver were fixed in 10% neutral buffered formalin and processed for light microscopical studies.Results: The result showed that TSE reduced the histopathological changes induced by the KCV in the muscles, livers, and kidneys, and the improvement was proportional to the applied dose of the TSE indicating that TSE prevents adverse histological changes in the muscle, liver, and kidney.Conclusion: The present study demonstrated that TSE reduced the histopathological changes in the muscle, liver, and kidney induced by KCV in mice.

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