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.
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.
Keyword:Acute kidney injury, inducible nitric oxide synthase, reactive oxygen species, unilateral nephrectomy, unilateral renal ischemia https://mc06.manuscriptcentral.com/cjpp-pubs AbstractAcute kidney injury is usually associated with distant organ dysfunction. The roles of inducible nitric oxide synthase (iNOS) and reactive oxygen species (ROS) in this phenomenon were investigated following 2-h unilateral renal ischemia and 24-h reperfusion. There were three groups of rats subjected to either unilateral ischemia/reperfusion (UIR group), unilateral nephrectomy (UNX group), or shamoperation. Two further groups were given α-tocopherol and aminoguanidine with UIR (treated-UIR group) and UNX (treated-UNX group). Plasma nitrite/nitrate and malondialdehyde were elevated only in the UIR group. Creatinine clearance and blood flow increased in non-ischemic kidney of the UIR, but not to the same extent as remnant kidney of the UNX group, while they had equal compensatory rises in absolute Na + -and K + -excretion and urine flow. Non-ischemic kidney of the treated-UIR group, but not remnant kidney of the treated-UNX group, showed more elevation in blood flow, whereas both kidneys had reductions in absolute Na + -excretion and urine flow.Respiratory functional variable were not different between all groups. Therefore, 2-h unilateral renal ischemia and 24-h reperfusion did not affect lung but had distant effects on contralateral kidney partly mediated by ROS and NO-derived from iNOS to dampen compensatory increases in renal hemodynamics and to decrease tubular reabsorption.Keywords: Acute kidney injury, acute lung injury, alpha-tocopherol, aminoguanidine, inducible nitric oxide synthase, ischemia/reperfusion, reactive oxygen species, unilateral nephrectomy, unilateral renal ischemia.
Background: Bleomycin-induced lung fibrosis has been accepted as an animal model for fibrosis in
Introduction: Resveratrol (trans-3,5,4’-trihydroxystilbene) as a polyphenol with potential antioxidant and anti-inflammatory properties is known as an effective herbal medicine in different disorders in rats. Objectives: The present study was carried out to investigate the protective effects of oral consumption of resveratrol on vanadium induced renal injury in male Wistar rats. Materials and Methods: Animals received either ammonium metavanadate (AMV, 5 mg/ kg/d, (intraperitoneally; 14 consecutive days) or resveratrol solution (10 mg/kg and 50 mg/kg, gastric gavage) along with AMV treatment. The last group received resveratrol alone (50 mg/ kg, gastric gavage) for 4 weeks. Results: AMV injection caused progressive tubular damages resembling acute tubular necrosis. Microscopic views revealed tubular attenuation and blebbing. In addition, progressive peritubular congestion of the capillaries observed while no evidence of renal fibrosis was present in trichrome staining. Further, levels of the renal transforming growth factor β1 (TGF-β1) as an index of fibrosis had no difference in treated animals as compared with the control (13.4±1.2 versus 11.24±0.93 pg/mg protein) at the P<0.05. However, in AMVtreated animals receiving the higher dose of resveratrol (50 mg/kg), the renal superoxide dismutase (SOD) activity, showed no difference as compared with the saline-treated rats (42±1.3 versus 51±1.4). Conclusions It is evident that AMV injection had no ability to induce renal fibrosis in rats while it evokes renal destructive lesions based on pathological results and enzyme levels. Moreover, our preliminary results suggest that resveratrol in high dose (50 mg/kg) could confer a minor role against AMV induced renal tubular necrosis in rats due to pathological results.
Purpose To determine the role of remote perconditioning (RPeC) on renal function and histology in an animal model of unilateral renal ischemia and reperfusion (IR) injury. Methods Rats were subjected to 60 min unilateral renal ischemia. RPeC protocol was the application of four cycles of 5 min IR of left femoral artery during renal ischemia. Assessments of histological changes and renal function were made 24 h, 1 week, or 3 weeks later. 99mTc-DMSA scan was performed using a small-animals SPECT system. Results 24-h reperfusion decreased the 99mTc-DMSA uptake in the left kidney compared to the intact kidney of control animals. RPeC group has higher uptake compared to the IR group. After 1 week and 3 weeks, uptakes were gradually increased in both groups and no differences were observed. Severe morphological changes in the ischemic kidneys of both groups were observed after 24 h which attenuated after 1 week and 3 weeks. Moreover, no differences in creatinine and BUN levels between IR-treated and intact animals were observed. Conclusion These data suggest that RPeC exerts a partially transient improvement in the renal function in the first day after reperfusion. However, long-term follow-up study showed no beneficial effects of RPeC. Moreover, noninvasive 99mTc-DMSA scan revealed a suitable tool in the follow-up evaluation of recovery process in the unilateral renal IR injury models.
Background: The purpose of this study was to compare the effects of saffron and methylprednisolone on bleomycin-induced pulmonary fibrosis in rats. Methods: This study was conducted in Bushehr, southern Iran in 2017.The animals were divided into four groups of five rats each. Three groups were injected with a single intratracheal dose of bleomycin (5 mg/kg). The fourth group was administered with normal saline at the same volume (200 µl). Saffron extract dissolved in water was given to one group (100 mg /body weight) orally while intraperitoneal injection of methylprednisolone (2.5 mg/kg) injected to another one for 16 days. The rats were sacrificed 28 days following surgery and their right and left lungs were removed and washed for measuring lung indices, myeloperoxidase activities and finally histopathological examination. Results: Injection of bleomycin caused decrement of body weight aggravated by intraperitoneal methylprednisolone treatment. Lung indices were increased in the bleomycin-treated group compared with the control, while methylprednisolone, unlike saffron, had no preventive effects on it. Both saffron and methylprednisolone treatment prevented the increase in lung myeloperoxidase as a destructive enzyme. In addition, excessive collagen deposition and thickening of alveolar septa were significantly prevented with saffron treatment as compared to methylprednisolone injection following hematoxylin and eosin staining. Conclusion: Saffron with established antioxidant properties could prevent some detrimental effects in bleomycin-induced pulmonary fibrosis even more than methylprednisolone injection known as a standard therapy in this murine model. More investigations must be carried out to examine the beneficial or harmful effects of this remedy.
Background In this study, we aimed to determine whether short-term treatment with PPAR-γ agonist pioglitazone could influence electrocardiogram (ECG) parameters and heart rate variability (HRV) in isoproterenol-induced cardiac ischemia at rest and after phenylephrine injection. Methods Male Sprague-Dawley rats were divided into Sham, pioglitazone (PIO, 3 mg/kg, i.p.), isoproterenol-induced cardiac ischemia (ISO, 150 mg/kg, subcutaneously at 24-hour intervals on days 4 and 5), and PIO + ISO groups. Saline (in the Sham and ISO groups) or pioglitazone (in the PIO and PIO + ISO groups) were administered for 5 days. On day 6, tracheostomy and cannulation of the femoral artery and vein were performed under deep anesthesia. Then, blood pressure (BP) and ECG were recorded and HRV analysed. Results Baroreflex induced by intravenous injection of phenylephrine (10 µg/0.1 ml) increased BP and decreased heart rate (HR) in all groups. HR, QT interval, and QTc in the ISO group were more than in the Sham group at baseline and in baroreflex. Pioglitazone decreased the mentioned parameters in the PIO + ISO group. HRV analysis showed reductions in parasympathetic components of HRV in the ISO group, whereas pioglitazone corrected it in the PIO + ISO group. Cardiac markers, malondialdehyde, white blood cells, and heart/body weight ratio were more in the ISO group than those in the Sham group. All mentioned parameters were lower in the PIO + ISO group than those in the ISO group. Conclusion We indicated pioglitazone improves the electrical conduction of the heart and HRV in cardiac ischemia through modulating the inflammatory reactions.
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