Rofecoxib decreases renal injury in obese Zucker rats

Dey, Aparajita; Maric, Christine; Kaesemeyer, Wayne H.; Zaharis, Constantine Z.; Stewart, Janet; Pollock, Jennifer S.; Imig, John D.

doi:10.1042/cs20040125

Cited by 47 publications

(54 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Prostaglandin I2 (PGI2) can oppose the deleterious TXA2 effects associated with chronic kidney disease [61]. A number of studies have linked obesity and type 2 diabetes to increased generation of COX-2 metabolites in the kidney [29,58,60]. A consistent finding in these studies has been a decreased PGI2/TXA2 ratio in diabetic patients and animal models of diabetes [62,67].…”

Section: Eicosanoids As a Therapeutic Target For Renal Damage In Cardsupporting

confidence: 61%

“…Likewise, inhibition of TX synthase preserved renal blood flow and slowed the progression renal damage in diabetic rats [62,67,69]. Rofecoxib, a COX-2 inhibitor, decreases vascular and glomerular damage when administered to obese Zucker rats [29]. This renal protection occurred even though body weights, blood glucose, and cholesterol levels were not affected by COX-2 inhibition [29].…”

Section: Eicosanoids As a Therapeutic Target For Renal Damage In Cardmentioning

confidence: 97%

“…Rofecoxib, a COX-2 inhibitor, decreases vascular and glomerular damage when administered to obese Zucker rats [29]. This renal protection occurred even though body weights, blood glucose, and cholesterol levels were not affected by COX-2 inhibition [29]. There could also be a connection between COX metabolites and oxidative stress in cardiometabolic syndrome.…”

Section: Eicosanoids As a Therapeutic Target For Renal Damage In Cardmentioning

confidence: 97%

“…Obese individuals and obese mice have an elevated renal plasma flow and GFR that can lead to an increased glomerular capillary pressure and glomerular injury [27,28]. Obese animal models have significant glomerular injury, including increased mesangial matrix, basement membrane thickening and mesangial cell expansion [29]. The hyperinsulinemia associated with obesity and cardiometabolic syndrome could be contributing to glomerular hypertrophy.…”

Section: Renal Damage and Cardiometabolic Syndromementioning

confidence: 99%

“…There could also be a connection between COX metabolites and oxidative stress in cardiometabolic syndrome. COX-2 inhibition has been demonstrated to decrease levels of the oxidative stress metabolite 8-isoprostane and this has been linked to decreased renal injury in obesity and hypertension [29,70]. Therefore, there is the potential for COX-2 inhibitors to be utilized as a treatment for renal injury associated with cardiometabolic syndrome.…”

Section: Eicosanoids As a Therapeutic Target For Renal Damage In Cardmentioning

confidence: 99%

See 4 more Smart Citations

Eicosanoids and renal damage in cardiometabolic syndrome

Imig

2008

Expert Opinion on Drug Metabolism & Toxicology

View full text Add to dashboard Cite

Obesity, hypertension and type 2 diabetes are major contributing factors to the increase in the number of patients that have chronic kidney disease. The clustering of visceral obesity and cardiovascular risk factors has been designated metabolic syndrome or cardiometabolic syndrome. Cardiometabolic syndrome is associated with a complex systemic inflammatory state that has been implicated in medically important complications including endothelial dysfunction. Inflammation, endothelial dysfunction, and insulin resistance are interrelated and have reciprocal relationships that link cardiovascular and metabolic diseases. Ultimately, cardiometabolic syndrome increases the risk for cardiovascular events and end organ damage. Although the number of patients with cardiometabolic syndrome is escalating, therapeutic approaches have not been developed that provide protection to the kidney. Eicosanoids are altered in cardiometabolic syndrome and contribute the progression of renal injury. The anti-hypertensive and anti-inflammatory actions of epoxides and soluble epoxide hydrolase inhibitors make these attractive eicosanoid therapeutic targets for chronic kidney disease in patients with cardiometabolic syndrome. Keywordskidney; epoxyeicosatrienoic acids; epoxide hydrolase; obesity; cytokines; inflammation Cardiometabolic SyndromeIn recent years, the number of obese people in the world is growing rapidly and has reached epidemic status. Obesity is the central phenotype in metabolic syndrome, also known as cardiometabolic syndrome that clusters with other cardiovascular risk factors. These other cardiovascular risk factors include hypertension, type 2 diabetes, insulin resistance, low high-density lipoproteins (HDL) cholesterol, elevated triglycerides, microalbuminuria, and atherosclerosis [1,2,3] (Figure 1). The Adult treatment Panel II of the National Cholesterol Education Program has defined metabolic syndrome as any three of the following five traits: visceral obesity, hypertension, hypertriglyceridemia, low HDL cholesterol, and impaired fasting glucose [4]. Although obesity is the phenotypic hallmark of cardiometabolic syndrome, the other risk factors that manifest in individuals varies greatly. Blood pressure elevation in obese individuals is closely related to weight gain; however, not all obese individuals become hypertensive [5][6][7][8]. The relationship between obesity and hypertension is well established but the exact consequences to end organ damage remains unknown. Interestingly, hypertension and diabetes account for seventy percent of patients with end stage renal disease (ESRD) and the number of patients with ESRD will double in this decade [9,10]. One of the main reasons for the doubling in ESRD patients is the increase in obesity related type 2 diabetes and its co-existence with hypertension.

show abstract

Section: Eicosanoids As a Therapeutic Target For Renal Damage In Cardsupporting

confidence: 61%

Section: Eicosanoids As a Therapeutic Target For Renal Damage In Cardmentioning

confidence: 97%

Section: Eicosanoids As a Therapeutic Target For Renal Damage In Cardmentioning

confidence: 97%

Section: Renal Damage and Cardiometabolic Syndromementioning

confidence: 99%

Section: Eicosanoids As a Therapeutic Target For Renal Damage In Cardmentioning

confidence: 99%

See 3 more Smart Citations

Eicosanoids and renal damage in cardiometabolic syndrome

Imig

2008

Expert Opinion on Drug Metabolism & Toxicology

View full text Add to dashboard Cite

show abstract

Cyclooxygenase Metabolites in the Kidney

Harris

Zhang

2011

Comprehensive Physiology

View full text Add to dashboard Cite

In the mammalian kidney, prostaglandins (PGs) are important mediators of physiologic processes, including modulation of vascular tone and salt and water. PGs arise from enzymatic metabolism of free arachidonic acid (AA), which is cleaved from membrane phospholipids by phospholipase A2 activity. The cyclooxygenase (COX) enzyme system is a major pathway for metabolism of AA in the kidney. COX are the enzymes responsible for the initial conversion of AA to PGG2 and subsequently to PGH2, which serves as the precursor for subsequent metabolism by PG and thromboxane synthases. In addition to high levels of expression of the "constitutive" rate-limiting enzyme responsible for prostanoid production, COX-1, the "inducible" isoform of cyclooxygenase, COX-2, is also constitutively expressed in the kidney and is highly regulated in response to alterations in intravascular volume. PGs and thromboxane A2 exert their biological functions predominantly through activation of specific 7-transmembrane G-protein-coupled receptors. COX metabolites have been shown to exert important physiologic functions in maintenance of renal blood flow, mediation of renin release and regulation of sodium excretion. In addition to physiologic regulation of prostanoid production in the kidney, increases in prostanoid production are also seen in a variety of inflammatory renal injuries, and COX metabolites may serve as mediators of inflammatory injury in renal disease.

show abstract

Lipidomic approaches to measuring isoprostanes and other markers of oxidative stress

Davies

2009

Euro J Lipid Sci & Tech

View full text Add to dashboard Cite

Oxidative stress shifts the normal physiological balance between the rate of formation and removal of reactive oxygen species (ROS) and leads to oxidative modification of a large number of macromolecules including lipids. Oxidative stress has been invoked as a potential mechanism in a wide variety of disease processes. One requirement for understanding the contribution of oxidative stress to disease is to quantitatively assess the resulting products during disease processes and potential interventions. ROS trigger a myriad of alterations in macromolecules, so that accurately measuring every possible alteration induced by oxidative stress is currently untenable. Therefore, quantifying specific products that are both representative of the formation of other products and that potentially directly participate in the disease process is a rational approach. This review focuses on one of the most commonly used biomarkers of oxidative stress, the F 2 -isoprostanes, and then discusses the value of simultaneously measuring other related lipid peroxidation products.

show abstract

Rofecoxib decreases renal injury in obese Zucker rats

Cited by 47 publications

References 55 publications

Eicosanoids and renal damage in cardiometabolic syndrome

Eicosanoids and renal damage in cardiometabolic syndrome

Cyclooxygenase Metabolites in the Kidney

Lipidomic approaches to measuring isoprostanes and other markers of oxidative stress

Contact Info

Product

Resources

About