The Effect of Levosimendan on Phosphine-Induced Nephrotoxicity: Biochemical and Histopathological Assessment

Drug Research ◽  
2021 ◽  
Author(s):  
Maryam Baeeri ◽  
Mahban Rahimifard ◽  
Maryam Armandeh ◽  
Behnaz Bameri ◽  
Madiha Khalid ◽  
...  

Abstract Background Aluminum phosphide (AlP) toxicity is associated with a high risk of death due to heart, liver, and kidney failure as the target organs. Phosphine gas released due to the ingestion is the main factor involved in the multi-organ failure with various mechanisms. Levosimendan (LEV) is a calcium sensitizer with a pleiotropic effect on multiple organs. This study aimed to investigate whether LEV can alleviate AlP-induced nephrotoxicity in the rat model. Method Six groups included control group (almond oil only), sole LEV group (48 µg/kg), AlP group (LD50=10 µg/kg), and the poisoned groups treated with LEV at doses of 12, 24, and 48 µg/kg 30 min after AlP gavage. After 24 hours of treatment, serum and kidney samples were taken for biochemical and histopathological analyses. Result Biochemical analysis of the AlP group showed that the activity of complexes I, II, and IV was significantly reduced, while the levels of lipid peroxidation (LPO) and reactive oxygen species (ROS), lactate, and myeloperoxidase (MPO) activity significantly increased. Also, AlP reduced live renal cells and elevated necrosis. However, the levels of serum creatinine and blood urea nitrogen were not affected by the poisoning. LEV co-treatment could increase mitochondrial complex activity and reduce MPO activity, LPO, ROS, and lactate levels. Additionally, the histopathological analysis showed the detrimental effects of AlP on kidney tissue, which was mitigated by LEV administration. Conclusion Our findings showed that LEV can potentially improve oxidative stress, imbalance in the redox status, necrosis, and pathological injuries in kidney tissue following AlP-poisoning.

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Hossein Sadeghi ◽  
Ehsan Karimizadeh ◽  
Heibatollah Sadeghi ◽  
Esmaeel Panahi kokhdan ◽  
Mahboubeh Mansourian ◽  
...  

Vancomycin-induced nephrotoxicity (VIN) has been reported to occur in 5–35% of recipient patients. The aims of the study were to evaluate protective effects of Rosa canina (RC) on VIN in rats. Rats were randomly divided into five groups as follows: control group I, group II (received VAN 400 mg/kg/day, every 12 h at doses of 200 mg/kg/day, for 7 consecutive days), group III (VAN + RC 250 mg/kg/day, for 7 consecutive days), group IV (VAN + RC 500 mg/kg/day, for consecutive days), and group V (received RC 500 mg/kg/day, for consecutive 7 days). On the eighth day after anesthetizing the animals, blood samples were taken from the heart, and then, the kidneys were removed to investigate kidney function, oxidative stress, and histopathological marker. Also, the chemical composition of RC extract was identified by GC-MS analysis. Oral dose of 500 mg/kg RC extract significantly reduced the serum levels of blood urea nitrogen (BUN), creatinine (Cr), malondialdehyde (MDA), and nitric oxide (NO) and also the kidney tissue MDA, protein carbonyl, and NO metabolites (nitrite) levels compared to the VAN-treated group ( P < 0.05 ). Based on histopathological analysis, RC extract at the dose of 500 mg/kg inhibited the destructive effects of VAN on kidney tissues. GC-MS analysis indicated that the main compositions were found to be lactose (21.96%), 3-t-butyloxaziridine (20.91%), and 5-oxymethylfurfurole (16.75%). The results indicated that oral administration of RC was able to reduce VAN-induced nephrotoxicity in rats, possibly through antioxidant pathways.


2020 ◽  
Vol 23 (5) ◽  
pp. 402-410 ◽  
Author(s):  
Lin-Zi Li ◽  
Shan-Shan Lei ◽  
Bo Li ◽  
Fu-Chen Zhou ◽  
Ye-Hui Chen ◽  
...  

Aim and Objective: The Dendrobium officinalis flower (DOF) is popular in China due to common belief in its anti-aging properties and positive effects on “nourish yin”. However, there have been relatively few confirmatory pharmacological experiments conducted to date. The aim of this work was to evaluate whether DOF has beneficial effects on learning and memory in senescent rats, and, if so, to determine its potential mechanism of effect. Materials and Methods: SD rats were administrated orally DOF at a dose of 1.38, or 0.46 g/kg once a day for 8 weeks. Two other groups included a healthy untreated control group and a senescent control group. During the 7th week, a Morris water maze test was performed to assess learning and memory. At the end of the experiment, serum and brain samples were collected to measure concentrations of antioxidant enzymes, including malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GSH-Px) in serum, and the neurotransmitters, including γ-aminobutyric acid (γ-GABA), Glutamic (Glu), and monoamine oxidase B (MAO-B) in the brain. Histopathology of the hippocampus was assessed using hematoxylin-eosin (H&E) staining. Results: The results suggested that treatment with DOF improved learning as measured by escape latency, total distance, and target quadrant time, and also increased levels of γ-GABA in the brain. In addition, DOF decreased the levels of MDA, Glu, and MAO-B, and improved SOD and GSHPx. Histopathological analysis showed that DOF also significantly reduced structural lesions and neurodegeneration in the hippocampus relative to untreated senescent rats. Conclusion: DOF alleviated brain aging and improved the spatial learning abilities in senescent rats, potentially by attenuating oxidative stress and thus reducing hippocampal damage and balancing the release of neurotransmitters.


2021 ◽  
Vol 10 (5) ◽  
pp. 1066
Author(s):  
Małgorzata Zalewska-Adamiec ◽  
Hanna Bachórzewska-Gajewska ◽  
Sławomir Dobrzycki

Background: The most serious complication of the acute Takotsubo phase is a myocardial perforation, which is rare, but it usually results in the death of the patient. Methods: In the years 2008–2020, 265 patients were added to the Podlasie Takotsubo Registry. Cardiac rupture was observed in five patients (1.89%), referred to as the Takotsubo syndrome with complications of cardiac rupture (TS+CR) group. The control group consisted of 50 consecutive patients with uncomplicated TS. The diagnosis of TS was based on the Mayo Clinic Criteria. Results: Cardiac rupture was observed in women with TS aged 74–88 years. Patients with TS and CR were older (82.20 vs. 64.84; p = 0.011), than the control group, and had higher troponin, creatine kinase, aspartate aminotransferase, and blood glucose levels (168.40 vs. 120.67; p = 0.010). The TS+CR group demonstrated a higher heart rate (95.75 vs. 68.38; p < 0.0001) and the Global Registry of Acute Coronary Events (GRACE) scores (186.20 vs. 121.24; p < 0.0001) than the control group. In patients with CR, ST segment elevation was recorded significantly more often in the III, V4, V5 and V6 leads. Left ventricular free wall rupture was noted in four patients, and in one case, rupture of the ventricular septum. In a multivariate logistic regression, the factors that increase the risk of CR in TS were high GRACE scores, and the presence of ST segment elevation in lead III. Conclusions: Cardiac rupture in TS is rare but is the most severe mechanical complication and is associated with a very high risk of death. The main risk factors for left ventricular perforation are female gender, older age, a higher concentration of cardiac enzymes, higher GRACE scores, and ST elevations shown using electrocardiogram (ECG).


2021 ◽  
Vol 53 (1) ◽  
Author(s):  
Emanuel M. Doroteu ◽  
Joao H. M. Viana ◽  
Jair A. Ferreira Junior ◽  
Juliana T. A. Macedo ◽  
Rodrigo A. Oliveira ◽  
...  

AbstractThe aim of this study was to compare testicle morpho-functional characteristics in bulls undergoing a single or two immunizations against GnRH. Nelore (Bos taurus indicus) bulls were randomly allocated into three experimental groups: G1 (n=12), a single 400 μg dose of anti-GnRH vaccine on day 0; G2 (n=11), a first 400 μg dose of anti-GnRH vaccine on day 0 followed by a second (boost) dose 30 days later; and control group (CG, n=12), 1 mL saline 0.9% at day 0. Every 30 days, from day 0 until slaughter at day 90, the bulls were weighed and underwent testicular biometry, semen collection and analysis, and blood sample collection for testosterone measurement. Immediately after slaughter, the testicles were removed and transport at 15°C to the laboratory for histopathological analysis. There was a decrease in testicular height (P=0.0476), width (P=0.0021), and in scrotal circumference (P=0.0001), after either a single (G1) or two (G2) immunizations against GnRH. Both G1 and G2 had lower testosterone concentrations than CG from day 60 on (P<0.01), but in G2, it was also lower than in G1 at day 90 (P=0.0006). All sperm parameters were affected by active immunization against GnRH (P<0.05), and in G2, averages were lesser (P<0.05) than in G1 from day 60 on. No signs of seminiferous tubule degeneration were found in any sample from the CG, contrasting with 75.0% and 100.0% of the samples from G1 and G2, respectively. In summary, immunocastration affected testicle morpho-functional characteristics in bulls in a time- and dose-dependent way.


Author(s):  
Robert Susło ◽  
Piotr Pobrotyn ◽  
Lidia Brydak ◽  
Łukasz Rypicz ◽  
Urszula Grata-Borkowska ◽  
...  

Introduction: Influenza infection is associated with potential serious complications, increased hospitalization rates, and a higher risk of death. Materials and Methods: A retrospective comparative analysis of selected indicators of hospitalization from the University Hospital in Wroclaw, Poland, was carried out on patients with confirmed influenza infection in comparison to a control group randomly selected from among all other patients hospitalized on the respective wards during the 2018–2019 influenza season. Results: The mean laboratory testing costs for the entire hospital were 3.74-fold higher and the mean imaging test costs were 4.02-fold higher for patients with confirmed influenza than for the control group; the hospital expenses were additionally raised by the cost of antiviral therapy, which is striking when compared against the cost of a single flu vaccine. During the 2018–2019 influenza season, influenza infections among the hospital patients temporarily limited the healthcare service availability in the institution, which resulted in reduced admission rates to the departments related to internal medicine; the mean absence among the hospital staff totaled approximately 7 h per employee, despite 7.3% of the staff having been vaccinated against influenza at the hospital’s expense. Conclusions: There were significant differences in the hospitalization indicators between the patients with confirmed influenza and the control group, which markedly increased the hospital care costs in this multi-specialty university hospital.


Pathobiology ◽  
2021 ◽  
pp. 1-12
Author(s):  
Ying Xie ◽  
Yuanyuan Ruan ◽  
Huimei Zou ◽  
Yixin Wang ◽  
Xin Wu ◽  
...  

<b><i>Objective:</i></b> The goal of the present study was to determine the expression of yes-associated protein 1 (YAP1) in renal tissues of mice with lupus nephritis (LN) and elucidate its role in the progression of renal fibrosis. <b><i>Methods:</i></b> C57BL/6 mice and MRL/lpr mice were selected for experimental comparison. Mouse kidney tissues were removed and sectioned for hematoxylin and eosin staining, Masson’s trichome staining, Sirius staining, and immunohistochemistry. The mRNA and protein levels of YAP1 in mouse kidney tissues were detected, and the correlation between YAP1 and fibronectin (FN) mRNA levels was analyzed. Mouse renal epithelial cells were used for in vitro experiments. After transfection and stimulation, the cells were divided into 4 groups, namely the C57BL/6 serum group (group 1), the MRL/lpr serum group (group 2), the MRL/lpr serum + siRNA-negative control group (group 3), and the MRL/lpr serum + siRNA-YAP1 group (group 4). Epithelial-mesenchymal transition (EMT) markers in each group were detected by Western blotting and immunofluorescence staining. Serum creatinine, blood urea nitrogen, and urinary protein levels were detected and assessed for their correlation with YAP1 mRNA levels by Spearman’s analysis. <b><i>Results:</i></b> Compared to C57BL/6 mice, MRL/lpr mice exhibited obvious changes in fibrosis in renal tissues. In addition, YAP1 expression was significantly higher in the renal tissues of MRL/lpr mice than in those of C57BL/6 mice, and YAP1 mRNA levels were positively correlated with those of FN. YAP1 silencing in lupus serum-stimulated cells could effectively relieve serum-induced EMT. Finally, we observed that YAP1 mRNA levels in mouse kidney tissue were significantly and positively correlated with the degree of renal function injury. <b><i>Conclusion:</i></b> YAP1 expression in the kidney tissues of LN mice was higher than that observed in normal mice, indicating that YAP1 may play an important role in the occurrence and development of LN.


Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
Jing Xu ◽  
Guanghui Zheng ◽  
Liangliang Wu ◽  
Xiangshao Fang ◽  
Yue Wang ◽  
...  

Introduction: Abnormal levels of end-tidal carbon dioxide (ETCO 2 ) may reflect a derangement in perfusion, metabolism, or gas exchange. It is unclear if ETCO 2 can be used for fluid resuscitation (FR) compared with traditional mean arterial pressure (MAP) as an outcome predictor in sepsis. Hypothesis: Use of ETCO2 is better than MAP in guiding fluid resuscitation to improve lactate levels and microcirculatory blood flow in sepsis. Methods: Thirty-five male Sprague-Dawley rats weighing 350-400g were randomized to: 1) SHAM, n=5; 2) cecal ligation and puncture (CLP) Control group (with CLP, without FR, n=10); 3) ETCO 2 group (with CLP, FR began when ETCO 2 ≤25 mmHg, n=10) and 4) MAP group (with CLP, FR began when MAP≤100 mmHg, n=10). Lactate level, cardiac output (CO), perfused small vessel density (PSVD) and sublingual microvascular flow index (MFI) was assessed at baseline, 2 h, 4 h, 8 h, 10 h and 12 h post-CLP. Survival duration was recorded. Results: After FR,CO in the ETCO 2 group increased compared with the MAP group 12h after CLP while lactate levels decreased compared with the Control and MAP groups (p<0.05) (Figure-1). Both sublingual PSVD and MFI decreased after CLP in the control group and MAP group but significantly improved in the ETCO 2 group 8h post-CLP. The average survival time in the ETCO 2 group was significantly greater than MAP group (Figure-2). Conclusions: ETCO 2 guided FR was associated with improved CO, lactate, microcirculatory flow, and survival time compared to MAP guided FR in a CLP-induced rat model of sepsis.


2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 477-477
Author(s):  
Myriam Kossai ◽  
Camélia Radulescu ◽  
Julien Adam ◽  
Anaïs Dziegielewski ◽  
Nicolas Signolle ◽  
...  

477 Background:Plasmacytoid urothelial carcinoma (UC) is a rare pathological variant of UC with low chemotherapeutic sensitivity and dismal outcomes. The molecular and immune profiles of such tumors remain poorly investigated. Herein, we investigated the phenotypical features of a cohort of plasmacytoid UC (n = 32) by comparison to a control group of conventional high-grade UC with matched clinicopathological characteristics (n = 30). Methods: Histopathological analysis included the following antibodies: p63, GATA3, CK5/6, CK20 and HER2. In addition, the density of intra-tumor CD8+ lymphocytes, and PD-L1 expression in tumor (TC) and immune cells (IC) were evaluated. Clinical data were collected. Results: Plasmacytoid UC expressed GATA3 (97% vs 86% p = 0.18), CK20 (59% vs 36% p = 0.08) markers and showed a significantly higher rate of HER2 overexpression (2+ and 3+ score: 25% vs 0%, p < 0.01) compared to controls. A significantly lower expression of CK5/6 (22% vs 56%, p < 0.05) and p63 (41% vs 80%, p < 0.05) was observed in plasmacytoid UC compared to controls. The density of tumor-infiltrating CD8+ cells was similar between plasmacytoid and conventional UC (p = 0.5). PD-L1 expression on IC was similar compared to conventional UC (p = 0.3). Overall survival at 5 years was significantly lower among patients with plasmacytoid UC compared to patients with conventional UC (p = 0.02). Conclusions: Together, our study demonstrated that plasmacytoid UC belong to the luminal subtype and display a rather inflamed microenvironment similar to conventional UC. These data support the inclusion of plasmacytoid variant of UC in clinical trials evaluating immune checkpoint inhibitors monotherapy or combination immunotherapeutic strategies.


2008 ◽  
Vol 23 (4) ◽  
pp. 364-371 ◽  
Author(s):  
Camila Maria Beder Ribeiro ◽  
Belmiro Cavalcanti do Egito Vasconcelos ◽  
Joaquim Celestino da Silva Neto ◽  
Valdemiro Amaro da Silva Júnior ◽  
Nancy Gurgel Figueiredo

PURPOSE: To analyze the action of gangliosides in peripheral nerve regeneration in the sciatic nerve of the rat. METHODS: The sample was composed of 96 male Wistar rats. The animals were anaesthetized and, after identification of the anaesthesic plane, an incision was made in the posterior region of the thigh, followed by skin and muscle divulsion. The right sciatic nerve was isolated and compressed for 2 minutes. Continuous suture of the skin was performed. The animals were randomly divided into two groups: the experimental group (EG), which received subcutaneous injection of gangliosides, and the control group (CG), which received saline solution (0.9%) to mimic the effects of drug administration. RESULTS: No differences were observed between the experimental and control groups evaluated on the eighth day of observation. At 15 and 30 days the EG showed an decrease in Schwann cell activity and an apparent improvement in fibre organization; at 60 days, there was a slight presence of Schwann cells in the endoneural space and the fibres were organized, indicating nerve regeneration. At 15 and 30 days, the level of cell reaction in the CG had diminished, but there were many cells with cytoplasm in activity and in mitosis; at 60 days, hyperplastic Schwann cells and mitotic activity were again observed, as well as nerve regeneration, but to a lesser extent than in the EG. CONCLUSION: The administration of exogenous gangliosides seems to improve nerve regeneration.


Author(s):  
Ari - Yuniarto

Objective: In the gastrointestinal system, gastric ulcer is one of the common serious problems in human life and gives contribution against morbidity and mortality incidence. The pathophysiology of gastric ulcer is an imbalance between aggressive factor and mucosal integrity factor. Increase of aggressive factors and decrease of mucosal integrity factors have potential against developed of gastric ulcer disease. The objective of the research was to evaluate antioxidant and gastric ulcer healing effect of Orthosiphon stamineus (Benth.) leaves extract in aspirin-induced rats.Methods: In vivo antiulcer activity of Orthosiphon leaves extract was evaluated through several parameters involves gastric acidity, number of ulcers, diameters of ulcers, ulcer index (UI), and healing ratio. Dose level of Orthosiphon leaves extract which used in this study such as 250 and500 mg/kg, respectively. Antioxidant activity of Orthosiphon leaves extract was evaluated by 1,1-diphenyl-2-picrylhydrazyl hydrate (DPPH) method. Histopathological of the stomach was performed using hematoxylin-eosin stained.Results: The results of the study showed that groups which given Orthosiphon leaves extract have significantly different for gastric ulcer healing compared to the control group and were supported by histopathological analysis. The Orthosiphon leaves extract also showed maximum scavengingactivity at a concentration of 100 µg/ml (58.86% inhibition) and minimum at 50 μg/ml (29.60% inhibition) with inhibitory concentration 50% (IC  )50 84.54 µg/ml when compared to ascorbic acid as the standard with IC5.08 µg/ml by DPPH method.Conclusion: It can be concluded that from the experimental study of O. stamineus (Benth.) leaves extract has potential antiulcer activity in aspirin- induced rats model and antioxidant effect using DPPH method. Stomach tissues regeneration in gastric ulcer model might be affected by the improvement of antioxidant status.Keywords: Orthosiphon stamineus (Benth.), Extract, Ulcer, Aspirin, 1,1-diphenyl-2-picrylhydrazyl hydrate.


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