The Effect of Hyperbaric Oxygen Treatment on the Renal Functions in Septic Rats: Relation to Oxidative Damage

Edremitlioğlu, Mustafa; Kılıç, Dilek; Öter, Şükrü; Kısa, Üçler; Korkmaz, Ahmet; Çoşkun, Ömer; Bedir, Orhan

doi:10.1007/s00595-004-3000-5

Cited by 30 publications

(28 citation statements)

References 40 publications

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“…In our study, LPS treatment caused a time-dependent pronounced arterial hypotension that was associated with tachycardia and ARF with reduced GFR, indicating the validity of our sepsis model. Fractional sodium excretion and tubular sodium reabsorption, both indicators of tubular function in this study, decreased after LPS injection, indicating tubular damage, which is in accordance with previous findings (29,30). Noteworthy, it has been shown that LPS infusion had an immediate antinatriuretic effect in the first hours after injection, leading subsequently to a marked increase in fractional sodium excretion, suggesting a delayed LPS-induced impairment in tubular sodium reabsorption and therefore confirming our results (31).…”

Section: Discussionsupporting

confidence: 93%

Regulation of Renal Sodium Transporters during Severe Inflammation

Schmidt¹,

Höcherl²,

Schweda

et al. 2007

Journal of the American Society of Nephrology

144

135

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Sepsis-associated acute renal failure is characterized by decreased GFR and tubular dysfunction. The pathogenesis of endotoxemic tubular dysfunction with failure in urine concentration and increased fractional sodium excretion is poorly understood. This study investigated the regulation of renal sodium transporters during severe inflammation in vivo and in vitro. Injection of high-dosage LPS reduced BP and GFR, increased fractional sodium excretion, and strongly decreased the expression of Na . ARF is present in 20% of patients with severe sepsis and 50% of patients with septic shock (2) and is clinically defined as a deterioration of GFR and tubular function. Little is known about the pathophysiology of endotoxemic tubular dysfunction with failure in urine concentration and increased fractional sodium excretion.Urine concentration requires establishment and maintenance of a hypertonic medullary interstitium, which depends on the NaCl reabsorption (3). The Na ϩ /H ϩ -exchanger (NHE3) and the functional unit of ROMK and Na ϩ -K ϩ -2Cl Ϫ co-transporter (NKCC2) are key components that are responsible for sodium reabsorption by the thick ascending limb (3,4). ROMK, also located in the cortical collecting duct (CCD), is responsible for recycling K ϩ across the apical membrane, which is critical for continuous sodium uptake by NKCC2 (5-8). In the collecting duct, the vasopressin-regulated epithelial sodium channel (ENaC), composed of three homologous subunits (9,10), accounts for the fine adjustment of the sodium reabsorption. The Na ϩ /K ϩ -ATPase in the basolateral membrane is essential for the efficient sodium reabsorption along the whole nephron.Findings that endotoxemia diminishes expression of renal V 2 receptors and aquaporin-2 (11) directed our interest toward the regulation of tubular sodium transporters during experimental sepsis. We hypothesized that endotoxemia downregulates tubular sodium transporters. On the basis of our previous findings that proinflammatory cytokines downregulate several vasoconstrictive receptors in renal tissue (12-15), we assumed that cytokines affect the expression of renal sodium transporters.To test our hypotheses, we performed in vivo experiments with (1) mice that were administered an injection of LPS as a model for severe experimental Gram-negative sepsis; (2) mice that were administered injections the cytokines TNF-␣, IL-1␤, or IFN-␥; (3) knockout mice that had a deficiency for TNF-␣, IL-1 receptor-1 (IL-1R1), or IFN-␥ and were administered an injection of LPS; (4) mice that did or did not have glucocorticoid pretreatment, which attenuates LPS-induced cytokine production (16 -18) and were administered an injection of LPS; (5) mice that were administered an injection of low-dosage LPS using as a model of inflammation without systemic hypotension and renal ischemia; (6) mice with renal artery clipping to reduce renocortical flux to 40% of controls to imitate LPS-induced renal hypoperfusion (19); and (7) mice with renal ischemia-reperfusion injury by complete renal artery occlus...

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Section: Discussionsupporting

confidence: 93%

Regulation of Renal Sodium Transporters during Severe Inflammation

Schmidt¹,

Höcherl²,

Schweda

et al. 2007

Journal of the American Society of Nephrology

144

135

View full text Add to dashboard Cite

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“…Fractional excretion of glucose and tubular glucose reabsorption were indicators of tubular function in this study. Decreased tubular glucose reabsorption with resulting glucosuria indicated tubular damage during experimental inflammation, which is in accordance with findings of previous investigations regarding tubular sodium reabsorption (16,39).…”

Section: Discussionsupporting

confidence: 92%

Regulation of renal glucose transporters during severe inflammation

Schmidt¹,

Höcherl²,

Bucher³

2007

American Journal of Physiology-Renal Physiology

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Schmidt C, Höcherl K, Bucher M. Regulation of renal glucose transporters during severe inflammation. Am J Physiol Renal Physiol 292: F804 -F811, 2007. First published October 10, 2006; doi:10.1152/ajprenal.00258.2006.-Severe sepsis is accompanied by acute renal failure (ARF) with renal tubular dysfunction and glucosuria. In this study, we aimed to determine the regulation of renal tubular glucose transporters during severe experimental inflammation. Male C57BL/6J mice were injected with LPS or proinflammatory cytokines, and renal perfusion, glomerular filtration rate (GFR), fractional glucose excretion, and expression of tubular glucose transporters were determined. We found a decreased plasma glucose concentration with impaired renal tissue perfusion and GFR and increased fractional glucose excretion associated with decreased expression of SGLT2, SGLT3, and GLUT2 after LPS injection. Similar alterations were observed after application of TNF-␣, IL-1␤, IL-6, or IFN-␥. To clarify the role of proinflammatory cytokines, we performed LPS injections in knockout mice with deficiencies for TNF-␣, IL-1 receptor type 1, IFN-␥, or IL-6 as well as LPS injections in glucocorticoidtreated wild-type mice. LPS-induced alterations of glucose transporters also were present in single-cytokine knockout mice. In contrast, glucocorticoid treatment clearly attenuated LPS-induced changes in renal glucose transporter expression and improved GFR and fractional glucose excretion. LPS-induced decrease of renal perfusion was not improved by glucocorticoids, indicating a minor role of ischemia in the development of septic renal dysfunction. Our results demonstrate modifications of tubular glucose transporters during severe inflammation that are probably mediated by proinflammatory cytokines and account for the development of ARF with increased fractional glucose excretion. In addition, our findings provide an explanation why single anti-cytokine strategies fail in the therapy of septic patients and contribute to an understanding of the beneficial effects of glucocorticoids on septic renal dysfunction.

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“…A recent report clearly illustrated the therapeutic effects of HBO on attenuating sepsis-induced kidney injury [16]. However, the other recent report demonstrated that HBO alone did not sufficiently attenuate sepsis-induced liver injury [17].…”

Section: Introductionmentioning

confidence: 98%