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

Chapela, Sebastián Pablo; Burgos, Isabel; Congost, Christian; Canzonieri, Romina; Muryan, Alexis; Alonso, Manuel; Stella, Carlos A.

doi:10.1155/2018/1928945

Cited by 14 publications

(19 citation statements)

References 42 publications

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“…In contrast, parenteral succinate administered in rats that did not undergo cecal ligation and puncture does not cause any changes regarding the Control group, suggesting that succinate does not affect non-septic rats. In previous studies, it has been documented that succinate reduces serum ROS levels, but it does not improve creatinine levels in septic rats [22], but the present research aimed to nd a correlation between serum ROS levels and serum apoptosis markers, also, the correlation between apoptosis markers and organ dysfunction markers as bilirubin and creatinine.…”

Section: Discussionmentioning

confidence: 88%

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Parenteral Succinate Reduces Levels of Reactive Oxygen Species, but It Does Not Reduce Caspase-3 Serum and Tissue Levels.

Chapela¹,

Muscogiuri²,

Barrea³

et al. 2021

Preprint

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Purpose: In sepsis Reactive Oxygen Species (ROS) production and apoptosis are two physiopathological processes that are increased. Succinate is a Krebs cycle intermediate that is reduced in Complex II of the mitochondria. This work aims to determine if succinate administration to septic rats improves serum ROS levels and serum and tissue levels of apoptosis. Methods: Sepsis was induced with cecal ligation and puncture in 200gr Sprague Dawley rats. 4 groups were formed (control, succinate, sepsis, and sepsis + succinate). 5mml/kg of intraperitoneal succinate were administered to the succinate and sepsis + succinate groups 2 h before sepsis induction and 2 h before sample taking. ROS levels were measured with dichlorofluorescein-diacetate, and apoptosis was measured with a Caspase-3 ELISA kit. Results: There were significant differences in serum ROS levels between the control group and the sepsis group (P = 0.012), but there were no differences in serum Caspase-3 levels (P = 0.15). The succinate administration reduced serum ROS levels in the sepsis + succinate group compared with the sepsis group in a statistically significant way (P = 0.004), but it did not reduce serum Caspase-3 levels (P = 0.39). There were no differences between groups in kidney and liver Caspase-3 levels. There was no correlation between serum ROS levels and serum Caspase-3 levels. Conclusions: In this model, ROS levels were reduced with succinate infusion, but Caspase-3 levels were not. In addition, ROS levels and apoptosis levels are not correlated, which suggests that those processes occur at different times.

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Section: Discussionmentioning

confidence: 88%

“…Different studies describe that succinate improved oxygen consumption in septic rat muscle [19], prolonged survival [20], and improved liver metabolic pro le [21]. In previous studies, it has been shown that succinate reduces ROS levels in septic rats [22].…”

Section: Introductionmentioning

confidence: 99%

Parenteral Succinate Reduces Levels of Reactive Oxygen Species, but It Does Not Reduce Caspase-3 Serum and Tissue Levels.

Chapela¹,

Muscogiuri²,

Barrea³

et al. 2021

Preprint

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“…The DCFH technique is an already described technique to measure intracellular ROS also in extracellular fluids [43][44][45][46]. It has been demonstrated in our laboratory that septic rats have higher levels of ROS than controls, and that the administration of parenteral succinate decreases ROS levels [35].…”

Section: Discussionmentioning

confidence: 99%

Serum reactive oxygen species and apoptosis markers in septic patients

Chapela¹,

Burgos²,

Schiel³

et al. 2021

ait

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Background: Oxidative stress is one of the pathophysiological processes that occur during sepsis. Reactive oxygen species (ROS) production causes lipid peroxidation and protein and DNA damage. ROS and DNA damage triggers apoptosis. Several studies have shown that organ failure in sepsis is mediated by apoptosis. The aim of this study is to investigate the levels of serum ROS and serum caspase-3 in septic patients and healthy volunteers, and their correlation.Methods: Serum samples were taken within the first 12 hours of ICU stay. The dichlorofluorescein technique was used to determine serum ROS levels, and the ELISA technique was used to quantify serum caspase-3 in septic patients and healthy volunteers.Results: There was no difference in serum ROS levels between healthy volunteers and septic patients (P = 0.26), and there was a significant difference in serum caspase-3 levels between healthy volunteers and septic patients (P < 0.001). There was no difference between patients who lived and died in the intensive care unit (ICU) in serum ROS (P = 0.089) and serum caspase-3 (P = 0.18). There was no correlation between both markers (R = -0.0013, P = 0.98). Conclusions:We conclude that there is no correlation between serum ROS and caspase-3; therefore, both processes might not be associated during the first hours of ICU stay.

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“…For example, arginine and proline metabolism is the core process of arginine, ornithine, proline, citrulline, and glutamate biosynthesis and metabolism [17]. Arginine is directly related to the production of nitric oxide in the body and participates in the regulation of end-stage renal degeneration [18-20]. In addition, the aminoacyl-tRNA biosynthesis pathway is related to oxidative stress, cell-cycle arrest, and apoptosis [21].…”

Section: Discussionmentioning

confidence: 99%

Ultra-Performance Liquid Chromatography-Q-Exactive Orbitrap-Mass Spectrometry Analysis for Metabolic Communication between Heart and Kidney in Adriamycin-Induced Nephropathy Rats

Wang

Liang

Yang

et al. 2021

Kidney Blood Press Res

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Background/Aims: Although the adriamycin-induced nephropathy model is frequently employed in the study of nephrotic syndrome and focal segmental glomerulosclerosis, the accompanying myocardial damage has always been a cause for concern. Therefore, there is a great need to study cardiorenal communication in this model. Methods: An adriamycin-induced nephropathy model was established via tail vein injection. The levels of the biochemical indicators serum albumin, serum globulin, serum total protein, serum cholesterol, serum creatinine (SCr), urinary protein, and urinary creatinine (UCr) were measured, and histopathological changes in the heart and kidneys were assessed using hematoxylin-eosin staining. Metabolomic changes in the heart, blood, and kidneys were analyzed using the metabolomics method based on ultra-performance liquid chromatography Q-Exactive Orbitrap mass spectrometry. Results: Compared with the control group, the model group showed significant decreases in serum protein and total protein levels, albumin/globulin ratio, and creatinine clearance rate as well as significant increases in serum cholesterol, SCr, urinary protein, and UCr levels. Significant pathological changes were observed in the renal pathology sections in the model group, including diffusely merged glomerular epithelial cells, inflammatory infiltration, and vacuolated glomerular cells. Additionally, thickened myocardial fibers, swollen nuclei, inflammatory infiltration, and partial myocardial necrosis could be seen in the cardiac pathology sections in the model group. Based on multivariate statistical analysis, a total of 20 differential metabolites associated with 15 metabolic pathways were identified in the heart, 7 differential metabolites with 7 metabolic pathways were identified in the blood, and 16 differential metabolites with 21 metabolic pathways were identified in the kidney. Moreover, 6 common metabolic pathways shared by the heart and kidney were identified: arginine and proline metabolism; arginine biosynthesis; glutathione metabolism; alanine, aspartate, and glutamate metabolism; beta-alanine metabolism; and histidine metabolism. Among these metabolic pathways, alanine, aspartate, and glutamate metabolism was shared by the heart, blood, and kidney. Succinic acid was found to be the key regulatory metabolite in cardiorenal metabolic communication. Conclusion: Six metabolic pathways were found to be involved in cardiorenal metabolic communication in an adriamycin-induced nephropathy model, in which alanine, aspartate, and glutamate metabolism may be the metabolic link between the heart and kidney in the development and maintenance of oxidative stress and inflammation. Succinic acid may serve as a key regulatory metabolic switch or marker of cardiac and renal co-injury, as shown in an adriamycin-induced nephropathy model.

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

Cited by 14 publications

References 42 publications

Parenteral Succinate Reduces Levels of Reactive Oxygen Species, but It Does Not Reduce Caspase-3 Serum and Tissue Levels.

Parenteral Succinate Reduces Levels of Reactive Oxygen Species, but It Does Not Reduce Caspase-3 Serum and Tissue Levels.

Serum reactive oxygen species and apoptosis markers in septic patients

Ultra-Performance Liquid Chromatography-Q-Exactive Orbitrap-Mass Spectrometry Analysis for Metabolic Communication between Heart and Kidney in Adriamycin-Induced Nephropathy Rats

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