Renal ischemia/reperfusion against nephrectomy for induction of acute lung injury in rats

Karimi, Zynab; Ketabchi, Farzaneh; Alebrahimdehkordi, Nasim; Fatemikia, Hossein; Owji, Seyed Mohammad; Moosavi, Seyed Mostafa Shid

doi:10.1080/0886022x.2016.1214149

Cited by 25 publications

(15 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…ALI after IR is characterized by increased vascular permeability, interstitial edema, alveolar hemorrhage, and red blood cells sludging [ 19 ]. HE staining in our study also exhibited the increase injury level in IR group mice.…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine attenuates lung apoptosis induced by renal ischemia–reperfusion injury through α2AR/PI3K/Akt pathway

Chen

et al. 2018

J Transl Med

View full text Add to dashboard Cite

BackgroundAcute lung injury caused by renal ischemia–reperfusion is one of the leading causes of acute kidney injury-related death. Dexmedetomidine, an α2-adrenergic agonist sedative, has been found to have protective effects against acute kidney injury and remote lung injury. We sought to determine whether dexmedetomidine can exert its anti-apoptotic effects in acute lung injury after acute kidney injury, in addition to its common anti-inflammatory effects, and to determine the underlying mechanisms.MethodsIn vivo, acute kidney injury was induced by 60 min of kidney ischemia (bilateral occlusion of renal pedicles) followed by 24 h of reperfusion. Mice received dexmedetomidine (25 µg/kg, i.p.) in the absence or presence of α2-adrenergic antagonist atipamezole (250 µg/kg, i.p.) before IR. Histological assessment of the lung was conducted by HE staining and arterial blood gases were measured. Lung apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay. The expression of caspase 3 and p-Akt in lung tissue was detected by western blot. In vitro, C57BL/6J mice pulmonary microvascular endothelial cells were treated with serum from mice obtained following sham or IR. Dexmedetomidine was given before serum stimulation in cells, alone or with atipamezole or LY294002. Cell viability was assessed by CCK 8 assay. Cell apoptosis was examined by Hoechst staining and Annexin V-FITC/PI staining flow cytometry analysis. Mitochondrial membrane potential was measured by flow cytometry. The expression of p-Akt, caspase 3, Bcl-2 and Bax was measured by western blot.ResultsIn vivo, dexmedetomidine remarkably mitigated pathohistological changes and apoptosis and significantly increased p-Akt expression in the lung. In addition, dexmedetomidine also slightly improved oxygenation in mice after IR, which can be abolished by atipamezole. In vitro, dexmedetomidine significantly inhibited IR serum-induced loss of viability and apoptosis in PMVECs. Dexmedetomidine increased p-Akt in a time- and dose-dependent manner, and down-regulated the expression of caspase 3 and Bax and up-regulated the Bcl-2 expression in PMVECs. The changes of MMP were also improved by dexmedetomidine. Whilst these effects were abolished by Atipamezole or LY294002.ConclusionOur results demonstrated that dexmedetomidine attenuates lung apoptosis induced by IR, at least in part, via α2AR/PI3K/Akt pathway.

show abstract

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine attenuates lung apoptosis induced by renal ischemia–reperfusion injury through α2AR/PI3K/Akt pathway

Chen

et al. 2018

J Transl Med

View full text Add to dashboard Cite

show abstract

“…Consequently, a pathologist colleague was asked to examine each section in at least 10 randomly selected non-overlapping fields under a light microscope in a blind manner. The renal histopathology was quantified for the degree of Bowman's space enlargement, tubular cell necrosis, exfoliated cells in the lumen, vascular congestion, and intratubular casts [33,34]. The level of each manifestation was graded according to the changes involved in comparison with the control group; scoring 0 for no changes, 1 for changes less than 20%, 2 for 20-40% of change, 3 for 40-60% of change, 4 for 60-80% of change, and 5 for greater than 80% of change compared to the control.…”

Section: Histopathological Examinationmentioning

confidence: 99%

Comparison of 99mTc-DMSA renal scintigraphy with biochemical and histopathological findings in animal models of acute kidney injury

et al. 2017

Self Cite

View full text Add to dashboard Cite

Biochemical and histological assays are currently used for the diagnosis and characterization of kidney injury. The purpose of this study was to compare technetium-99m-labeled dimercaptosuccinic acid (Tc-DMSA) renal scintigraphy, as a non-invasive method, with common biochemical and histopathological methods in two animal models of acute kidney injury. Nephrotoxicity was induced either by gentamicin (100 mg/kg/day for one week) or unilateral ureteral ligation (UUO). Renal scintigraphy was performed 1 h after intravenous injection of 99mTc-DMSA (3 mCi). Furthermore, plasma levels of blood urea nitrogen (BUN), creatinine, sodium, and potassium were determined using an autoanalyzer. At the end of experiments, kidneys were excised for the measurement of activity uptake (mCi/gr) using a dose calibrator as well as histopathological examinations with hematoxylin and eosin (H&E) staining. There was a significant decrease in 99mTc-DMSA uptake in both gentamicin (P value = 0.049) and UUO (P value = 0.034) groups, and it was more significant in the former. The levels of BUN and creatinine increased in both gentamicin and UUO groups, while the levels of sodium and potassium remained unchanged. Furthermore, a strong correlation was found between DMSA uptake and histopathological findings. Scintigraphy with 99mTc-DMSA is capable of detection of kidney injury in both gentamicin and UUO groups. Moreover, a significant correlation was found between scintigraphy parameters and histopathological findings. This suggests 99mTc-DMSA as a non-invasive method for the evaluation of kidney injury induced by drugs or anatomical disorders.

show abstract

“…Briefly, plasma samples and standards (1, 1,3,3-tetraethoxy propane, Sigma) were mixed with 0.25 N, HCl (Sigma), 20% tricholoro acetic acid (Sigma) and 0.8% tribarbituric acid (Sigma) incubated at 90°C for 60 min, cold in ice, and centrifuged at 4000 rpm for 10 min. Then, 200 μl of prepared solutions was added to each well, and the absorbance of well-plate was read at 532 nm using a microplate reader (Biotek, USA) [48].…”

Section: Mda Assaymentioning

confidence: 99%

Impact of liver damage on blood-borne variables and pulmonary hemodynamic responses to hypoxia and hyperoxia in anesthetized rats

Sepehrinezhad

Dehghanian

Rafati

et al. 2020

BMC Cardiovasc Disord

Self Cite

View full text Add to dashboard Cite

Background: Liver disorders may be associated with normal pulmonary hemodynamic, hepatopulmonary syndrome (HPS), or portopulmonary hypertension (POPH). In this study, we aimed to investigate the effect of the severity of liver dysfunctions on blood-borne variables, and pulmonary hemodynamic during repeated ventilation with hyperoxic and hypoxic gases. Methods: Female Sprague Dawley rats were assigned into four groups of Sham (n = 7), portal vein ligation (PPVL, n = 7), common bile duct ligation (CBDL, n = 7), and combination of them (CBDL+ PPVL, n = 7). Twenty-eight days later, right ventricular systolic pressure (RVSP) and systemic blood pressure were recorded in anesthetized animals subjected to repeated maneuvers of hyperoxia (O 2 50%) and hypoxia (O 2 10%). Besides, we assessed blood parameters and liver histology. Results: Liver histology score, liver enzymes, WBC and plasma malondialdehyde in the CBDL+PPVL group were higher than those in the CBDL group. Also, the plasma platelet level in the CBDL+PPVL group was lower than those in the other groups. On the other hand, the serum estradiol in the CBDL group was higher than that in the CBDL+PPVL group. All the above parameters in the PPVL group were similar to those in the Sham group. During ventilation with hyperoxia gas, RVSP in the CBDL+PPVL group was higher than the ones in the other groups, and in the CBDL group, it was more than those in the PPVL and Sham groups. Hypoxic pulmonary vasoconstriction (HPV) was not detected in both CBDL+PPVL and CBDL groups, whereas, it retained in the PPVL group. Conclusion: Severe liver damage increases RVSP in the CBDL+PPVL group linked to the high level of ROS, low levels of serum estradiol and platelets or a combination of them. Furthermore, the high RVSP at the noted group could present a reliable animal model for POPH in female rats.

show abstract

Renal ischemia/reperfusion against nephrectomy for induction of acute lung injury in rats

Abstract: Acutely accumulated systemic mediators following renal failure in the absence of kidneys vary from those due to combined renal failure with ischemic-reperfused kidneys and consequently they induce ALI with distinct characteristics.

Cited by 25 publications

References 36 publications

Dexmedetomidine attenuates lung apoptosis induced by renal ischemia–reperfusion injury through α2AR/PI3K/Akt pathway

Dexmedetomidine attenuates lung apoptosis induced by renal ischemia–reperfusion injury through α2AR/PI3K/Akt pathway

Comparison of 99mTc-DMSA renal scintigraphy with biochemical and histopathological findings in animal models of acute kidney injury

Impact of liver damage on blood-borne variables and pulmonary hemodynamic responses to hypoxia and hyperoxia in anesthetized rats

Contact Info

Product

Resources

About