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Sites of injection and blood sampling. Intraperitoneal (IP) (A) and subcutaneous (SC) (B) injections in mice. Blood samples were collected from the submandibular vein (C). Illustrated with BioRender. Full-size DOI: 10.7717/peerj.8328/fig-1
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Lactate treatment has shown a therapeutic potential for several neurological diseases, including Alzheimer’s disease. In order to optimize the administration of lactate for studies in mouse models, we compared blood lactate dynamics after intraperitoneal (IP) and subcutaneous (SC) injections. We used the 5xFAD mouse model for familial Alzheimer’s d...
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Context 1
... 5, 13, 37 min for the awake mice. The time course was extended to include 60 min for mice under anaesthesia to account for potentially delayed absorption and clearance rates. By puncturing the submandibular vein with a five mm long Goldenrod animal lancet (Braintree Scientific, Inc, MA, USA), 20 µl of blood was collected with a capillary tube (Fig. 1C) and immediately emptied into a pre-filled Eppendorf tube with haemolyzing solution (EKF Diagnostics, Cardiff, UK) with subsequent shaking. The samples were analyzed for lactate and glucose levels on a Biosen C-Line GP+ system (EKF Diagnostics, Cardiff, UK). Since it was challenging to collect blood samples at the exact same time points ...
Citations
... Gambar 3. 9. Pemberian obat secara Subkutan (SC) Sumber : (Haugen et al., 2020) 3. Intravena (IV) Suntikan obat intravena (IV) pada tikus merupakan prosedur pemberian obat dengan cara melakukan penyuntikan obat langsung ke bagian pembuluh darah utama, yaitu vena. Metode ini memungkinkan obat untuk langsung masuk pada area dalam aliran peredaran darah dan bisa langsung didistribusikan ke seluruh bagian tubuh. ...
... Tables 3 and 4 compared the glucose and lactate concentrations obtained from our DWE biosensor with previously reported glucose and lactate concentrations in blood. These values of glucose and lactate concentrations from normal mice and obese mice in our results were comparable with those of previously reported concentrations [33][34][35][36][37][38][39][40][41][42][43][44][45]. Increasing ratios were calculated with the following equation: Increasing ratio = Obese−Normal Normal × 100. ...
... However, changes in lactate were not significant during obesity monitoring because a relative short term of diet such as 8~12 weeks usually provided a negligible increase (0.5 mM, equivalent to 10% of increasing ratio) in lactate in the case of HFD-induced obesity [33,36,41]. Thus, our high increase (2.5 mM, equivalent to 61% of increasing ratio) of lactate in HFD-induced obesity would be a turning point to consider lactate as an important factor for obesity monitoring [42]. We suggested a new monitoring parameter in blood, the ratio of lactate to glucose (L/G), which reflects the influences of both glucose and lactate on obesity as a single parameter. ...
Understanding the levels of glucose (G) and lactate (L) in blood can help us regulate various chronic health conditions such as obesity. In this paper, we introduced an enzyme-based electrochemical biosensor adopting glucose oxidase and lactate oxidase on two working screen-printed carbon electrodes (SPCEs) to sequentially determine glucose and lactate concentrations in a single drop (~30 µL) of whole blood. We developed a diet-induced obesity (DIO) mouse model for 28 weeks and monitored the changes in blood glucose and lactate levels. A linear calibration curve for glucose and lactate concentrations in ranges from 0.5 to 35 mM and 0.5 to 25 mM was obtained with R-values of 0.99 and 0.97, respectively. A drastic increase in blood glucose and a small but significant increase in blood lactate were seen only in prolonged obese cases. The ratio of lactate concentration to glucose concentration (L/G) was calculated as the mouse’s gained weight. The results demonstrated that an L/G value of 0.59 could be used as a criterion to differentiate between normal and obesity conditions. With L/G and weight gain, we constructed a diagnostic plot that could categorize normal and obese health conditions into four different zones. The proposed dual electrode biosensor for glucose and lactate in mouse whole blood showed good stability, selectivity, sensitivity, and efficiency. Thus, we believe that this dual electrode biosensor and the diagnostic plot could be used as a sensitive analytical tool for diagnosing glucose and lactate biomarkers in clinics and for monitoring obesity.
... The use of the pyruvate agent can induce transient hypoxia and alter metabolism Takakusagi et al. 2014;Scroggins et al. 2018). It is interesting to note that a study found a difference in how mice of different stains, sex and anesthetic type processed lactate into glucose (Haugen et al. 2020). If choosing this methods there is possibility of mice and cell line dependence, so considerations must be taken. ...
Purpose
Tumors exhibit areas of decreased oxygenation due to malformed blood vessels. This low oxygen concentration decreases the effectiveness of radiation therapy, and the resulting poor perfusion can prevent drugs from reaching areas of the tumor. Tumor hypoxia is associated with poorer prognosis and disease progression and is therefore of interest to preclinical researchers. Although there are multiple different ways to measure tumor hypoxia and related factors, there is no standard for quantifying spatial and temporal tumor hypoxia distributions in preclinical research or in the clinic. This review compares imaging methods utilized for the purpose of assessing spatio-temporal patterns of hypoxia in the preclinical setting. Conclusions: Imaging methods provide varying levels of spatial and temporal resolution regarding different aspects of hypoxia, and with varying advantages and disadvantages. The choice of modality requires consideration of the specific experimental model, the nature of the required characterisation and the availability of complementary modalities as well as immunohistochemistry.
Introduction: Sepsis impaired vascular integrity results in multiple organ failure. Circulating lactate level is positively correlated with sepsis-induced mortality. We investigated whether lactate plays a role in causing endothelial barrier dysfunction in sepsis. Methods: Polymicrobial sepsis was induced in mice by cecal ligation and puncture (CLP). Lactic acid was injected i.p. (pH 6.8, 0.5 g/kg body weight) 6 h after CLP or sham surgery. To elucidate the role of heat shock protein A12B (HSPA12B), wild-type, HSPA12B-transgenic, and endothelial HSPA12B-deficient mice were subjected to CLP or sham surgery. To suppress lactate signaling, 3OBA (120 μM) was injected i.p. 3 h before surgery. Vascular permeability was evaluated with the Evans blue dye penetration assay. Results: We found that administration of lactate elevated CLP-induced vascular permeability. Vascular endothelial cadherin (VE-cadherin), claudin 5, and zonula occluden 1 (ZO-1) play a crucial role in the maintenance of endothelial cell junction and vascular integrity. Lactate administration significantly decreased VE-cadherin, claudin 5, and ZO-1 expression in the heart of septic mice. Our in vitro data showed that lactate (10 mM) treatment disrupted VE-cadherin, claudin 5, and ZO-1 in endothelial cells. Mechanistically, we observed that lactate promoted VE-cadherin endocytosis by reducing the expression of HSPA12B. Overexpression of HSPA12B prevented lactate-induced VE-cadherin disorganization. G protein-coupled receptor 81 (GPR81) is a specific receptor for lactate. Inhibition of GPR81 with its antagonist 3OBA attenuated vascular permeability and reversed HSPA12B expression in septic mice. Conclusions: The present study demonstrated a novel role of lactate in promoting vascular permeability by decreasing VE-cadherin junctions and tight junctions in endothelial cells. The deleterious effects of lactate in vascular hyperpermeability are mediated via HSPA12B- and GPR81-dependent signaling.
The mechanisms driving the pathologic state created by extracorporeal membrane oxygenation (ECMO) remain poorly defined. We developed the first complete blood-primed murine model of veno-arterial ECMO capable of maintaining oxygenation and perfusion, allowing molecular studies that are unavailable in larger animal models. Fifteen C57BL/6 mice underwent ECMO by cannulating the left common carotid artery and the right external jugular vein. The mean arterial pressure was measured through cannulation of the femoral artery. The blood-primed circuit functioned well. Hemodynamic parameters remained stable and blood gas analyses showed adequate oxygenation of the animals during ECMO over a 1-hour timeframe. A significant increase in plasma-free hemoglobin was observed following ECMO, likely secondary to hemolysis within the miniaturized circuit components. Paralleling clinical data, ECMO resulted in a significant increase in plasma levels of multiple proinflammatory cytokines as well as evidence of early signs of kidney and liver dysfunction. These results demonstrate that this novel, miniature blood-primed ECMO circuit represents a functional murine model of ECMO that will provide unique opportunities for further studies to expand our knowledge of ECMO-related pathologies using the wealth of available genetic, pharmacological, and biochemical murine reagents not available for other species.
Circulating lactate levels are a critical biomarker for sepsis and are positively correlated with sepsis-associated mortality. We investigated whether lactate plays a biological role in causing endothelial barrier dysfunction in sepsis. We showed that lactate causes vascular permeability and worsens organ dysfunction in CLP sepsis. Mechanistically, lactate induces ERK-dependent activation of calpain1/2 for VE-cadherin proteolytic cleavage, leading to the enhanced endocytosis of VE-cadherin in endothelial cells. In addition, we found that ERK2 interacts with VE-cadherin and stabilizes VE-cadherin complex in resting endothelial cells. Lactate-induced ERK2 phosphorylation promotes ERK2 disassociation from VE-cadherin. In vivo suppression of lactate production or genetic depletion of lactate receptor GPR81 mitigates vascular permeability and multiple organ injury and improves survival outcome in polymicrobial sepsis. Our study reveals that metabolic cross-talk between glycolysis-derived lactate and the endothelium plays a critical role in the pathophysiology of sepsis.
