Dexmedetomidine on renal ischemia-reperfusion injury in rats: assessment by means of NGAL and histology

Carvalho, Ana Lygia Rochitti de; Vital, Roberto; Kakuda, Cláudio Mueller; Bráz, José Reinaldo Cerqueira; Castiglia, Yara Marcondes Machado; Braz, Leandro Gobbo; Módolo, Marília Pinheiro; Domingues, Maria Aparecida Custódio; Módolo, Norma S. P.

doi:10.3109/0886022x.2015.1006118

Cited by 14 publications

(8 citation statements)

References 29 publications

(38 reference statements)

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“…After 90 min of reperfusion, both NGAL and L-FABP were increased in kidney tissue ( Figure 3D and E). An increase in NGAL following I/R in rats is in agreement with literature [93,94]. No studies could be retrieved for L-FABP in terms of renal I/R injury in rats, although urinary L-FABP levels were found to be predictive of the severity of AKI in mice [95].…”

Section: Tempol Reduces Ischemia/reperfusion-mediated Acute Kidney Insupporting

confidence: 85%

“…Juxtaposition of our result to literature plead for the first scenario, namely that 30/90 min I/R was in itself not very injurious to the kidney but ultimately led to AKI due to the contribution of hind limb I/R. In a study by de Carvalho et al [93], rats were subjected to 30-min renal artery clamping, after which NGAL and histological damage were determined in blood samples and by evaluation by a pathologist, respectively, at different reperfusion times. A moderate-to-severe damage profile, characterized by 25-50% tubular necrosis, was noted at 12-h reperfusion, which corresponded to a 3,636% increase in plasma NGAL compared to baseline after only renal artery occlusion [93].…”

Section: Tempol Improves Cortical and Medullary Microvascular Oxygenasupporting

confidence: 74%

“…In a study by de Carvalho et al [93], rats were subjected to 30-min renal artery clamping, after which NGAL and histological damage were determined in blood samples and by evaluation by a pathologist, respectively, at different reperfusion times. A moderate-to-severe damage profile, characterized by 25-50% tubular necrosis, was noted at 12-h reperfusion, which corresponded to a 3,636% increase in plasma NGAL compared to baseline after only renal artery occlusion [93]. By deduction, the 167% increase in tissue NGAL ( Figure 3D) reflects minimal histological damage.…”

Section: Tempol Improves Cortical and Medullary Microvascular Oxygenamentioning

confidence: 99%

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TEMPOL has limited protective effects on renal oxygenation and hemodynamics but reduces kidney damage and inflammation in a rat model of renal ischemia/reperfusion by aortic clamping

Ergin

Bezemer

Kandil

et al. 2015

JCTRes

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Background: Renal ischemia-reperfusion (I/R) is a common clinical complication in critically ill patients that is associated with considerable morbidity and mortality. Renal I/R is a major cause of acute kidney injury (AKI) resulting from I/R-induced oxidative stress, sterile inflammation, and microcirculatory perfusion defects, which can be ameliorated with the superoxide scavenger TEMPOL. The most common cause of AKI in the clinical setting is aortic surgery with suprarenal aortic clamping. The protective effect of TEMPOL in aortic clamping-induced renal I/R has not been studied before. Aim: To evaluate the protective effects of TEMPOL on oxidative stress, inflammation, tissue injury, and renal hemodynamics and oxygenation in a clinically representative rat model of I/R using aortic crossclamping. Methods: Animals (N = 24) were either sham-operated or subjected to ischemia (30 min) and 90-min reperfusion, with or without TEMPOL treatment (15 min before ischemia and during entire reperfusion phase, 200 μmol/kg/h). Systemic and renal hemodynamics, renal oxygenation, and blood gas values were determined at 15 min and 90 min of reperfusion. At 90-min reperfusion, iNOS, inflammation (IL-6, MPO), oxidative stress (MDA), and tissue damage (NGAL, L-FABP) were determined in tissue biopsies. Results: TEMPOL administration at a cumulative dose of 400 μmol/kg conferred a protective effect on AKI in terms of reducing renal damage, inflammation, and iNOS activation. With respect to renal hemodynamics and oxygenation, TEMPOL only reduced renal vascular resistance to near-baseline levels at both reperfusion time points and partially ameliorated the I/R-induced drop microvascular partial tension of oxygen at 90 min reperfusion. Also, TEMPOL alleviated the I/R-induced metabolic acidosis. However, TEMPOL exerted no restorative effect in terms of the severely reduced mean arterial pressure, renal blood flow, and renal oxygen delivery and consumption. The renal oxygen extraction ratio remained unchanged during the 90-min reperfusion phase. Kidneys in all groups were anuric throughout the experiment. Conclusions: This clinically representative renal I/R model, which entails both renal I/R and hind limb I/R as opposed to the standardly used renal I/R model that employs renal artery clamping, resulted in relatively moderate direct AKI. The damage was exacerbated by the perturbed systemic hemodynamics and metabolic acidosis as a result of the hind limb I/R. TEMPOL partially intervened in the factors that led to AKI as well as renal microvascular partial tension of oxygen and metabolic acidosis. However, more effective interventions should be devised for the mean arterial pressure drop (i.e., anuria) associated with aortic clamping and for restoring other critical renal hemodynamic and oxygenation parameters in order to improve post-I/R renal function. Relevance for patients: TEMPOL is a promising compound that has been shown to protect kidneys from I/R damage, which is relevant in kidney transplantation, pancreas transplantation, and ...

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Section: Tempol Reduces Ischemia/reperfusion-mediated Acute Kidney Insupporting

confidence: 85%

Section: Tempol Improves Cortical and Medullary Microvascular Oxygenasupporting

confidence: 74%

Section: Tempol Improves Cortical and Medullary Microvascular Oxygenamentioning

confidence: 99%

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TEMPOL has limited protective effects on renal oxygenation and hemodynamics but reduces kidney damage and inflammation in a rat model of renal ischemia/reperfusion by aortic clamping

Ergin

Bezemer

Kandil

et al. 2015

JCTRes

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“…In the NAC and NAC+DEX treatment groups, there were signifi cant regressions in nephrotoxic injury scores; however, DEX alone was not observed to cause amelioration in this score. Acute kidney injury is a complex and dynamic process (36). PGD2S is a new determinant of glomerular fi ltration rate.…”

Section: Discussionmentioning

confidence: 99%

Acute acetaminophene-induced hepatotoxicity and nephrotoxicity; therapeutic effect of dexmedetomidine

Taş¹,

Altınbaş²,

Noyan³

et al. 2019

BLL

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OBJECTIVE AND BACKGROUND: Acute acetaminophen (APAP) overdose has been shown to cause toxicity and the primary treatment medication is N-acetylcysteine (NAC). Dexmedetomidine (DEX) is a sedative drug with known antioxidant properties. We researched whether DEX has an injury-reducing effect on toxicity. METHODS: Rats were divided into: Group I (control), Group II (APAP) Group III (NAC) Group IV (DEX) and Group V (NAC+DEX). Histopathologic investigations of tissues were performed and glutathione peroxidase (GSH-Px), catalase (CAT), malondialdehyde (MDA), myeloperoxidase (MPO) and beta trace protein (PGD2S) levels were studied in blood samples. RESULTS: DEX administration for hepatotoxicity and nephrotoxicity induced with APAP, caused a signifi cant reduction in oxidative injury markers like MDA and MPO, a signifi cant increase in GSH-Px level and a signifi cant degree of amelioration in liver histopathologic scores. CONCLUSION: DEX administration for APAP toxicity causes a reduction in oxidative injury biomarkers, increased antioxidant biomarker levels and signifi cant reduction in liver histopathologic scores. The benefi cial effect of DEX use for detection of toxicity induced by acute APAP overdose, was shown in this study for the fi rst time (Tab. 5, Fig. 2, Ref. 41).

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“…In a study, cardioprotective effect of remifentanil via alpha and beta receptors had been shown 36. However, there have been no controlled studies for comparison of remifentanil and dex regarding their protective effects.…”

Section: Discussionmentioning

confidence: 99%

Does remifentanil attenuate renal ischemia–reperfusion injury better than dexmedetomidine in rat kidney?

Erkılıç¹,

Kesimci²,

Alaybeyoğlu³

et al. 2017

DDDT

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BackgroundIschemia–reperfusion (I/R) injury is a common cause of patient morbidity and mortality in the perioperative period. Patients undergoing long-lasting, abdominal, and urogenital surgeries with risk factors such as advanced age, peripheral artery disease, diabetes mellitus, renovascular disease, and congestive heart failure are candidates for acute kidney injury (AKI) due to impaired renal perfusion and decreased functional renal reserve. Pharmacological agents with multiple functions and anti-oxidative and anti-inflammation properties may be promising preventative strategies for AKI. Recently, dexmedetomidine (dex) has been postulated to have renoprotective effects.ObjectivesWe aimed to investigate the protective effects of an intravenous anesthetic remifentanil in renal I/R injury in the rat in comparison with dex.Materials and methodsA total of 30 Sprague Dawley adult rats were randomly assigned into five groups: the control group (group C, n=6), the sham group (group Sh, n=6, saline-infused rats without I/R injury), the saline group (group S, n=6, saline-infused rats with I/R injury), the remifentanil-treated group (group REM, n=6), and the dexmedetomidine-treated group (group DEX, n=6). The infusions (saline, remifentanil, and dex) were started after anesthesia induction and right nephrectomy and continued until the end of the surgical procedure. In I/R injury groups, the left renal artery and vein were occluded together by a clamp for 30 minutes and reperfusion lasted for 30 minutes. The rats were sacrificed after reperfusion, and the left kidney tissue was harvested. Blood samples were drawn from all animals to evaluate plasma neutrophil gelatinase-associated lipocalin (NGAL) at the beginning, 15 minutes after ischemia, 15 minutes after reperfusion, and 6 hours after the surgical procedure (T0, T1, T2, and T3, respectively).ResultsThe plasma NGAL levels exhibited increase at T1, T2, and T3 compared to the levels at T0 in group S (P<0.05). In group REM, there was a significant increase in plasma NGAL levels at T3 in comparison to those at T0, T1, and T2. The plasma NGAL levels at T2 in group S were significantly higher than those at T2 in group DEX (P<0.05). The groups S and REM showed significantly higher plasma NGAL levels at T3 compared to those at T0 (P<0.05). Upon histological examination, there was no difference among the study groups when left kidneys were evaluated (P>0.05).ConclusionThe NGAL levels and histopathological findings reflected protection by dex against renal I/R injury. However, the same exact results could not be mentioned for remifentanil depending on our study results.

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Dexmedetomidine on renal ischemia-reperfusion injury in rats: assessment by means of NGAL and histology

Abstract: The levels of NGAL did not indicate either protection against or worsening of kidney injury. Histological examination for acute tubular necrosis showed that dexmedetomidine did not protect the kidneys from I/R.

Cited by 14 publications

References 29 publications

TEMPOL has limited protective effects on renal oxygenation and hemodynamics but reduces kidney damage and inflammation in a rat model of renal ischemia/reperfusion by aortic clamping

TEMPOL has limited protective effects on renal oxygenation and hemodynamics but reduces kidney damage and inflammation in a rat model of renal ischemia/reperfusion by aortic clamping

Acute acetaminophene-induced hepatotoxicity and nephrotoxicity; therapeutic effect of dexmedetomidine

Does remifentanil attenuate renal ischemia–reperfusion injury better than dexmedetomidine in rat kidney?

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Dexmedetomidine on renal ischemia-reperfusion injury in rats: assessment by means of NGAL and histology

Abstract: The levels of NGAL did not indicate either protection against or worsening of kidney injury. Histological examination for acute tubular necrosis showed that dexmedetomidine did not protect the kidneys from I/R.

Cited by 14 publications

References 29 publications

TEMPOL has limited protective effects on renal oxygenation and hemodynamics but reduces kidney damage and inflammation in a rat model of renal ischemia/reperfusion by aortic clamping

TEMPOL has limited protective effects on renal oxygenation and hemodynamics but reduces kidney damage and inflammation in a rat model of renal ischemia/reperfusion by aortic clamping

Acute acetaminophene-induced hepatotoxicity and nephrotoxicity; therapeutic effect of dexmedetomidine

Does remifentanil attenuate renal ischemia&ndash;reperfusion injury better than dexmedetomidine in rat kidney?

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Does remifentanil attenuate renal ischemia–reperfusion injury better than dexmedetomidine in rat kidney?