Genetic suppression of HO-1 exacerbates renal damage: reversed by an increase in the antiapoptotic signaling pathway

2007 ◽  
Vol 292 (1) ◽  
pp. F148-F157 ◽  
Author(s):  
Rafal Olszanecki ◽  
Rita Rezzani ◽  
Shinji Omura ◽  
David E. Stec ◽  
Luigi Rodella ◽  
...  
Keyword(s):  
Renal Artery ◽  
Caspase 3 ◽  
Left Renal Artery ◽  
Protective Mechanism ◽  
Sprague Dawley ◽  
Antiapoptotic Proteins ◽  
Sprague Dawley Rats ◽  
Proapoptotic Protein ◽  
Cobalt Protoporphyrin ◽  
Cox 2

Apoptosis has been shown to contribute to the development of acute and chronic renal failure. The antiapoptotic action of the heme oxygenase (HO) system may represent an important protective mechanism in kidney pathology. We examined whether the lack of HO-1 would influence apoptosis in clipped kidneys of two-kidney, one-clip (2K1C) rats. Five-day-old Sprague-Dawley rats were injected in the left ventricle with ≈5 × 109 colony-forming units/ml of retrovirus containing rat HO-1 antisense (LSN-RHO-1-AS) or control retrovirus (LXSN). After 3 mo, a 0.25-mm U-shaped silver clip was placed around the left renal artery. Animals were killed 3 wk later. Clipping the renal artery in LSN-RHO-1-AS rats did not result in increased HO-1 expression. In contrast to LXSN animals, 2K1C LSN-RHO-1-AS rats showed increased expression of cyclooxygenase 2 (COX-2) and higher 3-nitrotyrosine (3-NT) content as well as increased expression of the proapoptotic protein Apaf-1 and caspase-3 activity. Clipping the renal artery in LXSN rats resulted in increased expression of the antiapoptotic proteins Bcl-2 and Bcl-xl, while clipping the renal artery in LSN-RHO-1-AS rats did not change Bcl-2 levels and decreased the levels of Bcl-xl. Treatment of LSN-RHO-1-AS rats with cobalt protoporphyrin resulted in induction of renal HO-1, which was accompanied by decreases in blood pressure, COX-2, 3-NT, and caspase-3 activity, and increased expression of anti-apoptotic molecules (Bcl-2, Bcl-xl, Akt and p-Akt) in the clipped kidneys. These findings underscore the prominent role of HO-1 in counteracting apoptosis in this 2K1C renovascular hypertension model.

scholarly journals Protection Effect of Self-Nanoemulsifying Drug Delivery System (SNEDDS) Piroxicam as Ulcerogenic Agent towards Malondialdehid Level and Protein Expression of Caspase-3, COX-1, COX-2 at Rat Gastric

2020 ◽  
pp. 273-283
Author(s):  
Iis Wahyuningsih ◽  
Kurnia Ambarwati ◽  
Erninda Ayu Hapsari ◽  
Afifah Fauziyyah ◽  
Azis Ikhsanudin ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Protein Expression ◽  
Drug Delivery System ◽  
Delivery System ◽  
Caspase 3 ◽  
Thiobarbituric Acid Reactive Substance ◽  
Sprague Dawley ◽  
Protection Effect ◽  
Cox 2 ◽  
Cox 1

The aim of this study was to determine the protection effect of SNEDDS piroxicam ulcerogenic agent against malondialdehyde (MDA) level and protein expression of caspase-3, COX-1, COX-2. The research was conducted using the test animals as much as 30 male white Sprague dawley (SD) rats aged 1-2 months with a weight of 100-200 grams divided into 5 groups. Treatment was given for 28 days orally. On the 29th day blood samples were also taken for the determination of MDA (Malondialdehid) levels by Thiobarbituric Acid Reactive Substance (TBARs) method using a visible spectrophotometer. Rats were sacrificed, then gastric organs were taken for immunohistochemical testing of caspase-3 and COX-1 expression, COX-2. The statistical analysis showed that the piroxicam SNEDDS group and the piroxicam suspension group decreased expression of the caspase-3 protein, increased COX-1 expression, decreased COX-2 and significantly decreased MDA levels. The piroxicam-containing SNEDDS (Self-Nanoemulsifying Drug Delivery System) form has protection against ulcogenic piroxicam.

A Novel Rat Model for Comprehensive Microvascular Training of End-to-End, End-to-Side, and Side-to-Side Anastomoses

2019 ◽  
Vol 35 (07) ◽  
pp. 499-504 ◽  
Author(s):  
Xiaoliang Yin ◽  
Gengfan Ye ◽  
Jun Lu ◽  
Lijun Wang ◽  
Peng Qi ◽  
...  
Keyword(s):  
Animal Model ◽  
Average Length ◽  
Proximal Part ◽  
Distal Portion ◽  
Left Renal Artery ◽  
Sprague Dawley ◽  
Anatomical Dissection ◽  
Sprague Dawley Rats ◽  
End To End ◽  
The Right

Background End-to-end, end-to-side, and side-to-side microvascular anastomoses are the main types of vascular bypass grafting used in microsurgery and neurosurgery. Currently, there has been no animal model available for practicing all three anastomoses in one operation. The aim of this study was to develop a novel animal model that utilizes the rat abdominal aorta (AA), common iliac arteries (CIAs), and the median sacral artery (MSA) for practicing these three types of anastomosis. Methods Eight adult Sprague–Dawley rats were anesthetized and then laparotomized. The AA, MSA, and bilateral CIAs were exposed and separated from the surrounding tissues. The length and diameter of each artery were measured. The relatively long segment of the AA without major branches was selected to perform end-to-end anastomosis. One side of the CIAs (or AA) and MSA were used for end-to-side anastomosis. The bilateral CIAs were applied to a side-to-side and another end-to-side anastomosis. Results Anatomical dissection of the AA, CIAs, and MSA was successfully performed on eight Sprague–Dawley rats; four arterial-to-arterial anastomoses were possible for each animal. The AA trunk between the left renal artery and right iliolumbar arteries was 15.60 ± 0.76 mm in length, 1.59 ± 0.15 mm in diameter, for an end-to-end anastomosis. The left CIA was 1.06 ± 0.08 mm in diameter, for an end-to-side anastomosis with the right CIA. The MSA was 0.78 ± 0.07 mm in diameter, for another end-to-side anastomosis with the right CIA or AA. After finishing end-to-side anastomosis in the proximal part of bilateral CIAs, the distal portion was juxtaposed for an average length of 5.6 ± 0.25 mm, for a side-to-side anastomosis. Conclusion This model can comprehensively and effectively simulate anastomosis used in revascularization procedures and can provide more opportunities for surgical education, which may lead to more routine use in microvascular anastomosis training.

Glomerular endothelin receptors during initiation and maintenance of ischemic acute renal failure in rats

1991 ◽  
Vol 260 (1) ◽  
pp. F110-F118
Author(s):  
B. M. Wilkes ◽  
A. R. Pearl ◽  
P. F. Mento ◽  
M. E. Maita ◽  
C. M. Macica ◽  
...  
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Acid Treatment ◽  
Affinity Constant ◽  
Left Renal Artery ◽  
Sprague Dawley ◽  
Receptor Sites ◽  
Sprague Dawley Rats ◽  
Receptor Number ◽  
Ischemic Acute Renal Failure

Glomerular endothelin (ET) receptors were studied in normal Sprague-Dawley rats and in rats with ischemic acute renal failure (ARF) induced by a 60-min occlusion of the left renal artery (right kidney intact). In normal rats ET bound to specific glomerular receptor sites [equilibrium affinity constant (Kd), 46.6 +/- 5.8 pM; receptor number (Ro), 1,167 +/- 160 fmol/mg (n = 7)]. ET infusion (90 ng.kg-1.min-1, intra-arterially) raised mean arterial pressure by 32 +/- 4 mmHg, lowered renal blood flow (RBF) by 62% and glomerular filtration rate (GFR) by 49%, and reduced the number of glomerular ET receptor sites by 62%. Reduced ET binding could not be explained by prior occupancy, because acid treatment (which dissociates bound ET from its receptors) did not increase receptor number. If elevated ET levels contributed to decreased RBF and GFR in ARF, glomerular ET receptors would be expected to down-regulate. In rats with ischemic ARF there were no differences in the number or affinity of glomerular ET receptors in the clamped or contralateral kidneys. Additional studies demonstrated that the downregulation response to ET infusion was intact in ARF. The data demonstrate that glomerular ET receptors are unaltered in ischemic ARF and do not support a role for increased glomerular ET in the alterations of renal hemodynamics in this model.

scholarly journals Sulodexide Protects Contrast-Induced Nephropathy in Sprague-Dawley Rats

2016 ◽  
Vol 40 (3-4) ◽  
pp. 621-632 ◽  
Author(s):  
Qing Zhao ◽  
Jianyong Yin ◽  
Zeyuan Lu ◽  
Yiwei Kong ◽  
Guangyuan Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Caspase 3 ◽  
Vehicle Group ◽  
Control Group ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Contrast Induced Nephropathy ◽  
Sprague Dawley Rats ◽  
Hk2 Cells

Background: Sulodexide is a powerful antithrombin agent with reno-protective property. However, whether it has beneficial effects on Contrast-Induced Nephropathy (CIN) remained elusive. In the current study, we evaluated the therapeutic effects of Sulodexide on CIN and investigated the potential mechanisms. Methods: CIN model was induced by intravenous injection of indomethacin, followed by Ioversol and L-NAME. Sprague-Dawley rats were divided into 4 groups: control group, CIN group, CIN+vehicle group (CIN rats pretreated with vehicle) and CIN+ Sulodexide (CIN rats pretreated with Sulodexide). Sulodexide or an equivalent volume of vehicle was intravenously delivered 30 min before the induction of CIN. All the animals were sacrificed at 24h after CIN and tissues were harvested to evaluate renal injury, kidney oxidative stress and apoptosis levels. Plasma antithrombin III (ATIII) activities were also measured. Results: Compared to the untreated CIN group, improved renal function, reduced tubular injury, decreased levels of oxidative stress and apoptosis were observed in CIN rats receiving Sulodexide injection. In addition, we also found that ATIII activity was significantly higher in Sulodexide-administered group than that in vehicle-injected CIN rats. For in vitro studies, HK2 cells were exposed to Ioversol and the cyto-protective effects of Sulodexide were also determined. Sulodexide pretreatment protected HK2 cells against the cytotoxicity of Ioversol via inhibiting caspase-3 activity. Preincubation with Sulodexide could also attenuate H2O2-induced increases in ROS, apoptosis and caspase-3 levels. Conclusions: Taken together, Sulodexide could protect against CIN through activating ATIII, and inhibiting oxidative stress, inflammation and apoptosis.

Low Dietary Salt Regulates Renal Vascular 20-Hydroxyeicosatetraenoic Acid Levels.

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 713-713
Author(s):  
Mairead A Carroll ◽  
Monica K Cheng ◽  
John C McGiff
Keyword(s):  
Sprague Dawley ◽  
Dietary Salt ◽  
Cox Inhibitors ◽  
Sprague Dawley Rats ◽  
On Line ◽  
Salt Depletion ◽  
Treatment Changes ◽  
Renal Microvasculature ◽  
Cox 2 ◽  
Renal Vascular

P110 20-hydroxyeicosatetraenoic (HETE), a prohypertensive cytochrome P450 (CYP)-derived arachidonic acid (AA) metabolite, is a principal eicosanoid of preglomerular microvessels. Vascular 20-HETE release is stimulated by angiotensin II (AII) and is subject to metabolism by cyclooxygenase (COX)-2. As dietary salt alters AII levels and COX-2 expression, we studied 20-HETE levels from microdissected arcuate and interlobular arteries and interlobar arteries obtained from male Sprague-Dawley rats fed a control (0.4% NaCl) or low salt diet (LS; 0.05% NaCl). In controls (n=6), metabolism of 14 C-AA (7μM) in the presence of NADPH (1mM) and indomethacin (INDO; 10μM) to 20-HETE was higher (P<0.05) in arcuate and interlobular arteries compared to interlobar arteries (25.2 ± 3.6 ng vs. 15.3 ± 2.3 ng/mg protein/30 min, respectively) based on reverse-phase HPLC retention times and on-line radiodetection. No regional differences in epoxide formation were evident between arcuate and interlobular arteries compared to interlobar arteries (21.9 ± 3.6 ng vs. 19.6 ± 3.7 ng/mg protein/30 min, respectively). LS treatment, for 7 days, selectively increased 20-HETE levels in interlobar arteries (24.6 ± 3.9 ng/mg protein/30 min) and increased medullary CYP-4A expression. However, in the absence of INDO, 20-HETE levels in arcuate and interlobular arteries, but not interlobar arteries, were diminished by 90% with LS treatment; changes that corresponded with induced cortical COX-2 expression. Thus, 20-HETE levels vary segmentally within the renal microvasculature. LS intake induces medullary CYP-4A expression and interlobar artery 20-HETE formation. Presumably, the diminished 20-HETE levels in arcuate and interlobular arteries, in the absence of COX inhibition, were a result of increased cortical COX-2 expression serving as a metabolic pathway for 20-HETE; the vasoconstrictor 20-HETE being metabolized by COX-2 to vasodilator prostaglandin analogs. Increased 20-HETE levels may account for the adverse effects of COX inhibitors with salt depletion.

Abstract 13522: Annexin-A1 Bioactive Peptide Ameliorates Cardiac Surgery-Associated Acute Kidney Injury (CSA-AKI) in Rats by Upregulating the Sirtuin6/FoxO3 Pathway

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Zhiquan Zhang ◽  
Qing Ma ◽  
Mihai V Podgoreanu
Keyword(s):  
Acute Kidney Injury ◽  
Cardiac Surgery ◽  
Caspase 3 ◽  
Kidney Injury ◽  
Positive Control ◽  
Annexin A1 ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Relevant Animal Model

Introduction: Acute kidney injury (AKI) is a prevalent and prognostically important complication of cardiac surgery. The complex multifactorial pathogenesis and lack of appropriate animal models to recapitulate the clinical insults leading to CSA-AKI have been implicated in the failure of multiple pharmacologic renoprotective strategies. We have reported anti-inflammatory and renoprotective effects of a novel Annexin-A1 (ANXA1) tripeptide (Ac-QAW) in a rodent model of experimental cardiac surgery. Here, we tested the hypothesis that Ac-QAW attenuates CSA-AKI by upregulating Sirtuin6 and Forkhead box protein O3 (SIRT6/FoxO3), key players in stress resistance, cell survival, and life span. Methods: Male Sprague-Dawley rats underwent 75 min of cardiopulmonary bypass (CPB) with 45 min of cardioplegic arrest (CA). Animals were treated (iv) with 1 mg/kg Ac-QAW (n = 6), the commercially available ANXA1 peptide Ac2-26 (as a positive control; n = 5), or vehicle (n = 6) at 1 h before CPB, during CA, and 1 h after CPB. At 24 h post-reperfusion, renal levels of activated caspase-3, ANXA1, SIRT6, and FoxO3 were determined by Western blot; renal and plasma levels of myeloperoxidase (MPO) were determined by ELISA. Results: At 24 hours post-reperfusion following CPB/CA, rats treated with Ac-QAW showed a) reduced renal caspase-3 activity (P < 0.05); b) decreased MPO in both blood and kidney; and c) increased renal levels of ANXA1 (P < 0.05), SIRT6, and FoxO3 (P < 0.01) (Figure). Conclusions: Using a clinically relevant animal model, we provide preliminary translatable evidence that administration of Ac-QAW attenuates CSA-AKI. This may result from action by Ac-QAW to 1) reduce inflammation by increasing inflammation-resolving molecule ANXA1; 2) inhibit neutrophil transmigration; and 3) promote pro-survival mechanisms by increasing SIRT6/FoxO3 expression. More Ac-QAW studies are needed to define its exact mechanism of action and its impact on long-term functional outcomes.

Sepsis induces an increase in thick ascending limb Cox-2 that is TLR4 dependent

2007 ◽  
Vol 293 (4) ◽  
pp. F1187-F1196 ◽  
Author(s):  
Tarek M. El-Achkar ◽  
Zoya Plotkin ◽  
Branislav Marcic ◽  
Pierre C. Dagher
Keyword(s):  
Rat Kidney ◽  
Cecal Ligation ◽  
Thick Ascending Limb ◽  
Wild Type ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Tlr4 Gene ◽  
Cox 2 ◽  
Tlr4 Activation ◽  
Induced Changes

Cyclooxygenase-2 (Cox-2) is an inducible enzyme responsible for the formation of inflammatory prostanoids such as prostaglandins and thromboxane. Its role in the pathophysiology of inflammatory states like sepsis is increasingly recognized. Recently, we demonstrated that sepsis upregulates the endotoxin receptor Toll-like receptor 4 (TLR4) in rat kidney. Because Cox-2 is one of the downstream products of TLR4 activation, we hypothesized that sepsis-induced changes in renal Cox-2 expression are TLR4 dependent. Indeed, we show that in Sprague-Dawley rats, cecal ligation and puncture (a sepsis model) increases Cox-2 expression in cortical and medullary thick ascending loops (cTAL and mTAL, respectively) as well as inner medullary collecting ducts. These are all sites of increased TLR4 expression during sepsis. To determine the actual dependence on TLR4, we measured Cox-2 expression in wild-type and mutant mice which harbor a TLR4 gene deletion ( TLR4−/−). In wild-type mice, sepsis increased Cox-2 expression in proximal tubules, cTAL, and mTAL. In contrast, septic TLR4−/− mice showed no significant increase in cTAL or mTAL Cox-2 expression. Furthermore, renin was absent from juxtaglomerular cells of TLR4−/− mice. We conclude that the dependence of sepsis-induced renal Cox-2 expression on TLR4 is tubule specific. The TLR4-dependent Cox-2 expression is mostly restricted to cortical and medullary thick ascending loops of Henle that characteristically express and secrete Tamm-Horsfall protein.

scholarly journals Inflammation and kidney injury attenuated by prior intake of Brazil nuts in the process of ischemia and reperfusion

2018 ◽  
Vol 40 (4) ◽  
pp. 312-318
Author(s):  
Maria Fernanda Ribeiro Cury ◽  
Estéfany Queiroz Olivares ◽  
Renata Correia Garcias ◽  
Giovana Queda Toledo ◽  
Natassia Alberici Anselmo ◽  
...  
Keyword(s):  
Cell Death ◽  
Caspase 3 ◽  
Cell Injury ◽  
Kidney Injury ◽  
Left Renal Artery ◽  
Ischemia And Reperfusion ◽  
Brazil Nuts ◽  
Markers Of Inflammation ◽  
Cox 2 ◽  
Renal Expression

ABSTRACT Introduction: Ischemia and reperfusion (IR) is a process inherent to the procedures involved in the transplantation of organs that causes inflammation, cell death and cell injury, and may lead to rejection of the graft. It is possible that the anti-inflammatory properties of the Brazil nuts (BN) can mitigate the renal injury caused by IR. Objective: To investigate whether the previous intake of BN reduces the expression of markers of inflammation, injury, and cell death after renal IR. Methods: Male Wistar rats were distributed into six groups (N = 6/group): SHAM (control), SHAM treated with 75 or 150 mg of BN, IR, and IR treated with 75 or 150 mg of BN. The IR procedure consisted of right nephrectomy and occlusion of the left renal artery with a non-traumatic vascular clamp for 30 min. BN was given daily from day 1 to 7 before surgery (SHAM or IR), and maintained until sacrifice (48 h after surgery). Inflammation was evaluated by renal expression of COX-2 and TGF-β, injury by the expression of vimentin, and cell death by apoptosis through caspase-3 expression (immunohistochemistry). Results: Pretreatment with 75 mg of BN reduced renal expression of the COX-2, TGF-β, vimentin, and caspase-3. The dose of 150 mg caused increased expression of COX-2. Conclusion: In experimental IR, the damage can be minimized with a prior low-dose intake of BN, improving inflammation, injury, and cell death.

scholarly journals IMPACT OF ZOLEDRONATE BISPHOSPHONATE GEL IN VIRGIN COCONUT OIL ON THE INCREASE OF OSTEOCLAST APOPTOSIS

2018 ◽  
Vol 9 ◽  
pp. 24
Author(s):  
Carolin Parlina ◽  
Erni H Purwaningsih ◽  
Ahmad Aulia Jusuf ◽  
Retno Widayati
Keyword(s):  
Buccal Mucosa ◽  
Caspase 3 ◽  
Coconut Oil ◽  
Control Group ◽  
Sprague Dawley ◽  
Emulsion Gel ◽  
Sprague Dawley Rats ◽  
The Impact ◽  
Experimental Group ◽  
Osteoclast Apoptosis

Objective: This study aimed to show the impact of the ZOL in VCO gel (Ge-ZOL) on the extent of osteoclasts apoptosis.Methods: The study used 27 Sprague-Dawley rats which were divided into three groups: Nine rats in the experimental group were given 40 µg of Ge-ZOL, nine rats in the control group were given VCO emulsion gel without ZOL (Ge-), and nine rats in the normal group were not given any treatment. The gel was applied to the buccal mucosa using a cotton bud for 2 min at hour of 0, 4, and 8 on days 0, 1, 2, 3, and 4. The rats were sacrificed on days 1, 3, and 5, and then, evaluated by immunohistochemical caspase-3 staining.Result: The number of apoptotic osteoclast cells in the experimental group was significantly higher than in the control and normal groups (p<0.05). The number of apoptotic osteoclast cells in the experimental group on the day 1 was significantly higher than on the days 3 and 5 (p<0.001).Conclusion: The application of Ge-ZOL to the buccal mucosa proven to improve the number of apoptotic osteoclast cells in the experimental group on the day 1, and this number was higher than on the days 3 and 5.

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