Oxidative stress contributes to orthopedic trauma-induced acute kidney injury in obese rats

Mittwede, Peter N.; Xiang, Lusha; Lu, Silu; Clemmer, John S.; Hester, Robert L.

doi:10.1152/ajprenal.00537.2014

Cited by 22 publications

(27 citation statements)

References 59 publications

(1 reference statement)

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“…Reactive oxygen species play an important role in mediating innate immune responses, including activation of damage-associated molecular pattern molecules, neutrophil priming, stimulation of oxidant-related transcription factors and molecular events, and production of cytokines and chemokines. Interestingly, we found that antioxidant treatment decreases lung neutrophil numbers, myeloperoxidase activity, and plasma interleukin-6 levels in obese Zucker rats following trauma, suggesting that exacerbated oxidative stress in obesity facilitates or exaggerates immune responses (58, 96). In addition, we found that the pulmonary microvasculature in obese Zucker rats exhibit increased basal permeability and is more vulnerable to elevated oxidative stress as compared to lean Zucker rats (58, 96).…”

Section: Obesity and Animal Models Of Critical Illnessmentioning

confidence: 85%

“…Additionally, we observed significant increases in systemic, lung, and renal inflammation and oxidative stress the day after trauma in obese rats, and the inhibition of NADPH oxidase (NOX), a major source of superoxide, prevented the development of both lung and kidney injury in the obese Zucker rats but had no effect in lean rats (58, 96). These results suggest that trauma increases the incidence of kidney and lung injury in obesity due, at least in part, to exacerbated oxidative stress.…”

Section: Obesity and Animal Models Of Critical Illnessmentioning

confidence: 89%

“…We have shown that the day after orthopedic trauma, obese rats exhibit increased incidences of acute lung and acute kidney injury, the two most-frequent organ injuries observed in trauma patients. This is evidenced by the presence of greater lung inflammation and pulmonary edema, decreased glomerular filtration rate and renal plasma flow, and increased urine excretion of renal damage markers in obese Zucker rats as compared to their lean counterparts (58, 96). This is in agreement with the clinical literature, which has consistently demonstrated an increased risk of multiple organ (especial lung and kidney) dysfunction, injury, and failure in obese blunt trauma patients (11, 20).…”

Section: Obesity and Animal Models Of Critical Illnessmentioning

confidence: 99%

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Obesity and Critical Illness

Mittwede

Clemmer

Bergin

et al. 2016

Shock

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Critical illness is a major cause of morbidity and mortality around the world. While obesity is often detrimental in the context of trauma, it is paradoxically associated with improved outcomes in some septic patients. The reasons for these disparate outcomes are not well understood. A number of animal models have been used to study the obese response to various forms of critical illness. Just as there have been many animal models that have attempted to mimic clinical conditions, there are many clinical scenarios that can occur in the highly heterogeneous critically ill patient population that occupies hospitals and intensive care units. This poses a formidable challenge for clinicians and researchers attempting to understand the mechanisms of disease and develop appropriate therapies and treatment algorithms for specific subsets of patients, including the obese. The development of new, and the modification of existing animal models is important in order to bring effective treatments to a wide range of patients. Not only do experimental variables need to be matched as closely as possible to clinical scenarios, but animal models with pre-existing comorbid conditions need to be studied. This review briefly summarizes animal models of hemorrhage, blunt trauma, traumatic brain injury, and sepsis. It also discusses what has been learned through the use of obese models to study the pathophysiology of critical illness in light of what has been demonstrated in the clinical literature.

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Section: Obesity and Animal Models Of Critical Illnessmentioning

confidence: 85%

Section: Obesity and Animal Models Of Critical Illnessmentioning

confidence: 89%

Section: Obesity and Animal Models Of Critical Illnessmentioning

confidence: 99%

See 1 more Smart Citation

Obesity and Critical Illness

Mittwede

Clemmer

Bergin

et al. 2016

Shock

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“…[25][26][27] In post-traumatic AKI in obese rats, SOD activity was reported to be suppressed. 28 It has been reported that in AKI patients, the NADPH oxidase p22phox gene polymorphism was associated with dialysis requirements and death. 29 In our study, it was similarly determined that gene polymorphism of CAT, an antioxidant enzyme, was also related to intensive care requirements and in-hospital mortality.…”

Section: Discussionmentioning

confidence: 99%

Manganese superoxide dismutase, glutathione peroxidase and catalase gene polymorphisms and clinical outcomes in acute kidney injury

Kıdır

Yiğit

et al. 2016

Renal Failure

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Introduction The aim of this study was to evaluate the potential association of single gene polymorphisms of manganese superoxide dismutase (MnSOD), glutathione peroxidase 1 (GPX1) and catalase (CAT) with clinical outcomes of acute kidney injury (AKI). Materials and methods Ninety AKI patients and 101 healthy volunteers were included in the study. Determination of MnSOD rs4880, GPX1 rs1050450 and CAT rs769217 polymorphisms was performed using real-time polymerase chain reaction amplification. The duration of hospitalization of AKI patients, dialysis and intensive care requirements, sepsis, oliguria and in-hospital mortality rates were assessed. Results The MnSOD, GPX1 and CAT genotypes and allele frequencies of AKI patients did not differ significantly from those of healthy controls. In patients with a T allele in the ninth exon of the CAT gene, intensive care requirements were greater than those of patients with the CC genotype (p ¼ 0.04). In addition, sepsis and in-hospital mortality were observed significantly more frequently in patients with a T allele in the ninth exon of the CAT gene (p ¼ 0.03). Logistic regression analysis determined that bearing a T allele was the primary determinant of intensive care requirements and in-hospital mortality, independent of patient age, gender, presence of diabetes and dialysis requirements (OR 6.10, 95% CI 1.34-27.81, p ¼ 0.02 and OR 10.25, 95% CI 1.13-92.80, p ¼ 0.04, respectively). Conclusion Among AKI patients in the Turkish population, hospital morbidity and mortality were found to be more frequent in patients bearing a T allele of the rs769217 polymorphism of the CAT gene.

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“…Large recent studies indicate that obese patients have an increased mortality risk following trauma (3), so it would be interesting to compare differences between outcomes in trauma versus other critically ill patients who are obese, as these demographics would likely have disparate malnutrition profiles as well as a different burden of comorbid conditions. We have recently shown that following orthopedic trauma, obese rats have an increased risk of developing acute lung and kidney injury, and that these are mediated by exacerbated hyperglycemic, inflammatory, and oxidative stress responses in obese as compared to nonobese rodents (4, 5). Clinical studies have shown that these variables are also associated with poor outcomes in the critically ill.…”

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confidence: 99%