scholarly journals Sevoflurane exerts brain-protective effects against sepsis-associated encephalopathy and memory impairment through caspase 3/9 and Bax/Bcl signaling pathway in a rat model of sepsis

2018 ◽  
Vol 46 (7) ◽  
pp. 2828-2842 ◽  
Author(s):  
Nurdan Bedirli ◽  
Emin Umit Bagriacik ◽  
Guldal Yilmaz ◽  
Zerrin Ozkose ◽  
Mustafa Kavutçu ◽  
...  
Keyword(s):  
Rat Model ◽  
Memory Impairment ◽  
Caspase 3 ◽  
Cecal Ligation ◽  
Weight Ratio ◽  
Dry Weight ◽  
Protective Effects ◽  
Tissue Samples ◽  
Isoflurane Group ◽  
Experimental Rat Model

Objective We compared the effects of sevoflurane and isoflurane on systemic inflammation, sepsis-associated encephalopathy, and memory impairment in a rat sepsis model of cecal ligation and puncture (CLP)-induced polymicrobial peritonitis. Methods Twenty-four rats were assigned to sham, CLP, CLP + sevoflurane, and CLP + isoflurane groups. At 72 hours after CLP, the rats underwent behavior tests. Serum cytokines were evaluated. Brain tissue samples were collected for determination of glutathione peroxidase (GPX), superoxide dismutase (SOD), and catalase; the wet/dry weight ratio; myeloperoxidase (MPO) and malondialdehyde (MDA); apoptotic gene release; and histologic examinations. Results The MPO level, wet/dry weight ratio, and histopathology scores were lower and the Bcl2a1 and Bcl2l2 expressions were upregulated in both the CLP + sevoflurane and CLP + isoflurane groups compared with the CLP group. The interleukin-6, interleukin-1β, MDA, and caspase 3, 8, and 9 levels were lower; the GPX, SOD, Bax, Bcl2, and Bclx levels were higher; and non-associative and aversive memory were improved in the CLP + sevoflurane group compared with the CLP + isoflurane group. Conclusion Sevoflurane decreased apoptosis and oxidative injury and improved memory in this experimental rat model of CLP. Sevoflurane sedation may protect against brain injury and memory impairment in septic patients.

scholarly journals Protective effects of taxifolin on pazopanib-induced liver toxicity: an experimental rat model

2020 ◽  
Author(s):  
Baran AKAGUNDUZ ◽  
Muhammet OZER ◽  
Fatih OZCICEK ◽  
Ali Veysel KARA ◽  
Sahin LACIN ◽  
...  
Keyword(s):  
Rat Model ◽  
Liver Toxicity ◽  
Protective Effects ◽  
Experimental Rat Model

scholarly journals Endothelin receptor antagonist improves donor lung function in an ex vivo perfusion system

2020 ◽  
Vol 27 (1) ◽  
Author(s):  
K. Walweel ◽  
K. Skeggs ◽  
A. C. Boon ◽  
L. E. See Hoe ◽  
M. Bouquet ◽  
...  
Keyword(s):  
Gas Exchange ◽  
Partial Pressure ◽  
Ex Vivo ◽  
Weight Ratio ◽  
Dry Weight ◽  
Lung Damage ◽  
Endothelin Receptor ◽  
Donor Pool ◽  
Ex Vivo Lung Perfusion ◽  
Tissue Samples

Abstract Background A lung transplant is the last resort treatment for many patients with advanced lung disease. The majority of donated lungs come from donors following brain death (BD). The endothelin axis is upregulated in the blood and lung of the donor after BD resulting in systemic inflammation, lung damage and poor lung graft outcomes in the recipient. Tezosentan (endothelin receptor blocker) improves the pulmonary haemodynamic profile; however, it induces adverse effects on other organs at high doses. Application of ex vivo lung perfusion (EVLP) allows the development of organ-specific hormone resuscitation, to maximise and optimise the donor pool. Therefore, we investigate whether the combination of EVLP and tezosentan administration could improve the quality of donor lungs in a clinically relevant 6-h ovine model of brain stem death (BSD). Methods After 6 h of BSD, lungs obtained from 12 sheep were divided into two groups, control and tezosentan-treated group, and cannulated for EVLP. The lungs were monitored for 6 h and lung perfusate and tissue samples were processed and analysed. Blood gas variables were measured in perfusate samples as well as total proteins and pro-inflammatory biomarkers, IL-6 and IL-8. Lung tissues were collected at the end of EVLP experiments for histology analysis and wet-dry weight ratio (a measure of oedema). Results Our results showed a significant improvement in gas exchange [elevated partial pressure of oxygen (P = 0.02) and reduced partial pressure of carbon dioxide (P = 0.03)] in tezosentan-treated lungs compared to controls. However, the lungs hematoxylin–eosin staining histology results showed minimum lung injuries and there was no difference between both control and tezosentan-treated lungs. Similarly, IL-6 and IL-8 levels in lung perfusate showed no difference between control and tezosentan-treated lungs throughout the EVLP. Histological and tissue analysis showed a non-significant reduction in wet/dry weight ratio in tezosentan-treated lung tissues (P = 0.09) when compared to control. Conclusions These data indicate that administration of tezosentan could improve pulmonary gas exchange during EVLP.

scholarly journals Activation of caspase-3 may not contribute to postresuscitation myocardial dysfunction

2009 ◽  
Vol 296 (4) ◽  
pp. H1164-H1174 ◽  
Author(s):  
Jeejabai Radhakrishnan ◽  
Iyad M. Ayoub ◽  
Raúl J. Gazmuri
Keyword(s):  
Cytochrome C ◽  
Dna Fragmentation ◽  
Rat Model ◽  
Caspase 3 ◽  
Myocardial Dysfunction ◽  
Left Ventricular ◽  
Stroke Work ◽  
Protective Effects ◽  
Apoptotic Pathway ◽  
Apoptosis Protein

We have previously reported that postresuscitation myocardial dysfunction is accompanied by the release of cytochrome c and caspase-3 activation. We now investigated the role of caspase-3 activation by examining whether such process prompts apoptotic DNA fragmentation, whether caspase-3 inhibition attenuates myocardial dysfunction, and whether myocardial protective effects of sodium-hydrogen exchanger isoform-1 (NHE-1) inhibition involve caspase-3 inhibition using a rat model of ventricular fibrillation (VF) of closed-chest resuscitation. Resuscitation after 4 or 8 min of untreated VF caused significant reductions in left ventricular stroke work index averaging 23% of sham control rats at 4 h postresuscitation. Left ventricular dysfunction was accompanied by increases in cytosolic cytochrome c, decreases in pro- and cleaved caspase-9 fragments, increases in 17-kDa caspase-3 fragments, and increases in caspase-3 activity indicating the activation of the mitochondrial apoptotic pathway but without evidence of apoptotic DNA fragmentation. In addition, levels of heat shock protein 70 were increased and levels of X-linked inhibitor of apoptosis protein and αβ-crystallin were preserved, all of which can exert antiapoptotic effects. In a separate series, the caspase-3 inhibitor z-Asp-Glu-Val-Asp chloromethyl ketone given before the induction of VF failed to prevent postresuscitation myocardial dysfunction despite reductions in caspase-3 activity (2.3 ± 0.5 vs. 1.3 ± 0.5 pmol fluorophore AFC released·mg protein−1·min−1; P < 0.03). Treatment with the NHE-1 inhibitor cariporide had no effect on caspase-3 activity. Accordingly, in this rat model of VF and severe postresuscitation myocardial dysfunction, activation of caspase-3 did not lead to DNA fragmentation or contribute to myocardial dysfunction. Concomitant activation of intrinsic antiapoptotic mechanisms could play a protective role downstream to caspase-3 activation.

scholarly journals Alda-1 Prevents Pulmonary Epithelial Barrier Dysfunction following Severe Hemorrhagic Shock through Clearance of Reactive Aldehydes

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Tianfeng Hua ◽  
Min Yang ◽  
Yangyang Zhou ◽  
Limin Chen ◽  
Huimei Wu ◽  
...  
Keyword(s):  
Lung Injury ◽  
Hemorrhagic Shock ◽  
Rat Model ◽  
Weight Ratio ◽  
Dry Weight ◽  
Epithelial Barrier ◽  
Lung Edema ◽  
Epithelial Tissue ◽  
Diffuse Infiltration ◽  
Reactive Aldehydes

Severe hemorrhagic shock and resuscitation (HS/R) can lead to lung injury, resulting in respiratory insufficiency. We investigated whether treatment with Alda-1, an ALDH2 activator, decreased lung injury induced by severe HS/R in a rat model. Male Sprague-Dawley rats were randomized into three groups, hemorrhagic shock + placebo, hemorrhagic shock + Alda-1, and sham. All animals were heparinized, and then 50% of the total calculated blood volume was collected over 60 minutes. After 40 minutes of hemorrhagic shock, animals were reinfused with the shed blood over 40 minutes and then observed for an additional 2 hours. Concentrations of 4-HNE, TNF-α, IL-6, and ALDH2 activity were detected; lung injury and lung wet-to-dry weight ratios were assessed. Expression of occludin and ZO-1 proteins in lung tissues was also determined. At 2 hours after resuscitation, lung injury was significantly reduced and the wet-to-dry weight ratio was notably decreased in the Alda-1 group compared with placebo (P<0.05). Alda-1 treatment also significantly increased the activity of ALDH2 and decreased the levels of toxic 4-HNE (P<0.05). In the Alda-1 group, IL-6 and TNF-α were dramatically decreased compared with placebo-treated animals (P<0.05). Expression of occludin and ZO-1 proteins was significantly decreased in the placebo group compared with the Alda-1 group (P<0.05). Thus, in a rat model of severe HS/R, treatment with Alda-1 increased the activity of ALDH2, significantly accelerated the clearance of reactive aldehydes, and concomitantly alleviated lung injury through improvement of pulmonary epithelial barrier integrity resulting in decreased alveolar epithelial tissue permeability, lung edema, and diffuse infiltration of inflammatory cells.

Attenuation of hyperoxic lung injury by the 21-aminosteroid U-74389G

1995 ◽  
Vol 78 (5) ◽  
pp. 1635-1641 ◽  
Author(s):  
S. Tasaka ◽  
A. Ishizaka ◽  
T. Urano ◽  
K. Sayama ◽  
F. Sakamaki ◽  
...  
Keyword(s):  
Lung Injury ◽  
Lung Tissue ◽  
Guinea Pigs ◽  
Weight Ratio ◽  
Dry Weight ◽  
Endothelial Damage ◽  
Lung Water ◽  
Tissue Samples ◽  
Cell Accumulation ◽  
Hyperoxic Lung Injury

Hyperoxic lung injury is attributable to oxygen radicals produced under hyperoxic conditions. The 21-aminosteroid (AS), U-74389G, is a potent antioxidant. We examined the effect of U-74389G on lung injury in guinea pigs during exposure to 90% O2 for 48 h. We injected either vehicle or 10 mg/kg of U-74389G 30 min before the O2 exposure and injected the same dose 12, 24, and 36 h later. We performed two series of experiments after exposure. In the first series, we measured the clearance rate of 99mTc-labeled dialdehyde starch (DAS) from the lungs as an index of pulmonary epithelial damage in three experimental groups consisting of 1) control (n = 6) O2 alone (n = 6), and 3) O2 + AS (n = 6). In the second series, pulmonary endothelial injury was estimated by using 28 guinea pigs divided into four experimental groups consisting of 1) control (n = 8), 2) AS alone (n = 5), 3) O2 alone (n = 6), and 4) O2 + AS (n = 9). In the second series, we measured the wet-to-dry weight ratio (W/D) as an index of lung water and the concentration ratio of 125I-labeled albumin in lung tissue and bronchoalveolar lavage (BAL) fluid compared with plasma (T/P and BAL/P, respectively) as indexes of pulmonary endothelial damage. Cell accumulation in BAL fluid and lung tissue samples was also assessed in the second series.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Ganoderic acid A attenuates lipopolysaccharide-induced lung injury in mice

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Bing Wan ◽  
Yan Li ◽  
Shuangshuang Sun ◽  
Yang Yang ◽  
Yanling LV ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Mouse Model ◽  
Weight Ratio ◽  
Dry Weight ◽  
Lavage Fluid ◽  
Myeloperoxidase Activity ◽  
Protective Effects ◽  
Ganoderic Acid ◽  
Lower Lung

Abstract The present study aimed to investigate the protective effects of ganoderic acid A (GAA) on lipopolysaccharide (LPS)-induced acute lung injury. In mouse model of LPS-induced acute lung injury, we found that GAA led to significantly lower lung wet-to-dry weight ratio and lung myeloperoxidase activity, and attenuated pathological damages. In addition, GAA increased superoxide dismutase activity, but decreased malondialdehyde content and proinflammatory cytokines levels in the bronchoalveolar lavage fluid. Mechanistically, GAA reduced the activation of Rho/ROCK/NF-κB pathway to inhibit LPS-induced inflammation. In conclusion, our study suggests that GAA attenuates acute lung injury in mouse model via the inhibition of Rho/ROCK/NF-κB pathway.

scholarly journals Lactate as a Potential Biomarker of Sepsis in a Rat Cecal Ligation and Puncture Model

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Xiaozhu Zhai ◽  
Zhengfei Yang ◽  
Guanghui Zheng ◽  
Tao Yu ◽  
Peng Wang ◽  
...  
Keyword(s):  
Troponin I ◽  
Cecal Ligation ◽  
Weight Ratio ◽  
High Mobility ◽  
Dry Weight ◽  
Cecal Ligation And Puncture ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Potential Biomarker ◽  
Puncture Model

We attempted to investigate whether blood lactate is a useful biomarker for sepsis in a rat cecal ligation and puncture (CLP) model. Male Sprague-Dawley rats underwent approximately 75% cecum ligation and two punctures to induce high-grade sepsis. A lactate of 1.64 mmol/L (Youden score of 0.722) was selected as the best cutoff value to predict the onset of sepsis after CLP exposure; 46 of 50 rats who survived 24 hours after the CLP were divided into the L group (lactate < 1.64 mmol/L) and M group (lactate ≥ 1.64 mmol/L). In the M group, the animals had significantly higher murine sepsis scores and none survived 5 days post-CLP, and the rate of validated septic animals, serum procalcitonin, high mobility group box 1, blood urea nitrogen, alanine transaminase, cardiac troponin I, and the wet-to-dry weight ratio were significantly higher compared to the L group. Worsen PaO2/FiO2, microcirculations, and mean arterial pressure were observed in the M group. More severe damage in major organs was confirmed by histopathological scores in the M group compared with the L group. In conclusion, lactate ≥ 1.64 mmol/L might serve as a potential biomarker to identify the onset of sepsis in a rat CLP model.

Argon Delays Initiation of Liver Regeneration after Partial Hepatectomy in Rats

2017 ◽  
Vol 58 (5-6) ◽  
pp. 204-215 ◽  
Author(s):  
Tom Florian Ulmer ◽  
Athanassious Fragoulis ◽  
Henriette Dohmeier ◽  
Andreas Kroh ◽  
Anne Andert ◽  
...  
Keyword(s):  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Noble Gas ◽  
Ischemia Reperfusion ◽  
Weight Ratio ◽  
Hepatocyte Proliferation ◽  
Protective Effects ◽  
Test Results ◽  
Ki 67 ◽  
Tissue Samples

Background: The liver can heal up to restitutio ad integrum following damage resulting from various causes. Different studies have demonstrated the protective effect of argon on various cells and organs. To the best of our knowledge, the organ-protective effects of the noble gas argon on the liver have not yet been investigated, although argon appears to influence signal paths that are well-known mediators of liver regeneration. We hypothesized that argon inhalation prior to partial hepatectomy (70%) has a positive effect on the initiation of liver regeneration in rats. Methods: Partial hepatectomy (70%) with or without inhaled argon (50 vol%) was performed for 1 h. Liver tissue was harvested after 3, 36, and 96 h to analyze the mRNA and protein expression of hepatocyte growth factor (HGF), interleukin-6 (IL-6), tumor necrosis factor-α, and extracellular signal-regulated kinase 1/2. Histological tissue samples were prepared for immunohistochemistry (bromodeoxyuridine [BrdU], Ki-67, and TUNEL) and blood was analyzed regarding the effects of argon on liver function. Statistical analyses were performed using 1-way ANOVA followed by the post hoc Tukey-Kramer test. Results: After 3 h, the primary outcome parameter of hepatocyte proliferation was significantly reduced with argon 50 vol% inhalation in comparison to nitrogen inhalation (BrdU: 15.7 ± 9.7 vs. 7.7 ± 3.1 positive cells/1,000 hepatocytes, p = 0.013; Ki-67: 17.6 ± 13.3 vs. 4.7 ± 5.4 positive cells/1,000 hepatocytes, p = 0.006). This was most likely mediated by significant downregulation of HGF (after 3 h: 5.2 ± 3.2 vs. 2.3 ± 1.0 fold, p = 0.032; after 96 h: 2.1 ± 0.5 vs. 1.3 ± 0.3 fold, p = 0.029) and IL-6 (after 3 h: 43.7 ± 39.6 vs. 8.5 ± 9.2 fold, p = 0.032). Nevertheless, we could detect no significant effect on the weight of the residual liver, liver-body weight ratio, or liver blood test results after argon inhalation. Conclusion: Impairment of liver regeneration was apparent after argon 50 vol% inhalation that was most probably mediated by downregulation of HGF and IL-6 in the initial phase. However, the present study was not adequately powered to prove that argon has detrimental effects on the liver. Further studies are needed to evaluate the effects of argon on livers with preexisting conditions as well as on ischemia-reperfusion models.

scholarly journals Protective Effects of Atorvastatin and Rosuvastatin on 3,4-methylenedioxymethamphetamine (MDMA)-Induced Spatial Learning and Memory Impairment

2021 ◽  
Author(s):  
Majid Eslami ◽  
Laleh Khorshidi ◽  
Maryam Ghasemi ◽  
Amir Rashidian ◽  
Mahdi Mirghazanfari ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Memory Impairment ◽  
Caspase 3 ◽  
Spatial Learning And Memory ◽  
Ros Production ◽  
Protective Effects ◽  
Memory Functions ◽  
Male Wistar Rats ◽  
Coa Reductase ◽  
Hippocampal Apoptosis

Abstract 3,4‐methylenedioxymethamphetamine (MDMA) or "Ecstasy", which has been used for recreational purposes, is shown to cause learning and memory impairment. Statins, beyond their efficient cholesterol-lowering action through inhibition of 3-hydroxy-3-methylglutaryl-CoA (HMG-COA) reductase, possess multiple neuroprotective impacts referred to as pleiotropic effects. In this regard, we aimed to investigate the protective effect of atorvastatin and rosuvastatin in MDMA-induced neurotoxicity. Adult male Wistar rats received atorvastatin (5, 10, 20 mg/kg; orally) and rosuvastatin (5, 10, 20 mg/kg; orally) for 21 consecutive days. Then, Morris water maze (MWM) was performed to examine learning and memory functions. Rats were injected with MDMA (2.5, 5, and 10 mg/kg; I.P) 30 min before training sessions in 4 training days of MWM task. Afterward, rats were sacrificed under general anesthesia and their hippocampuses were dissected to evaluate reactive oxygen species (ROS) production, lipid peroxidation (LPO), and caspase-3 and -9 activities. Our Findings showed that MDMA impaired spatial memory functions and dramatically upregulated ROS production, LPO, and caspase-3 and 9 activities. Also, atorvastatin (5, 10, 20 mg/kg) and rosuvastatin (20 mg/kg) significantly improved memory performances and inhibited upregulation of ROS, LPO, and caspase-3 and -9 activities induced by MDMA. In conclusion, the amelioration of MDMA-induced memory impairment and hippocampal apoptosis through atorvastatin and rosuvastatin could be accredited to the observed suppression of ROS production, LPO, and caspase-3 and -9 activities, since excessive exposure of hippocampus to oxidative stress enhanced apoptotic caspases activities, promoted to neuronal apoptosis.

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