scholarly journals In vitro Evaluation of Linezolid and Doripenem Clearance with Different Hemofilters

2020 ◽  
Vol 49 (3) ◽  
pp. 295-301 ◽  
Author(s):  
Toshihisa Hiraiwa ◽  
Kazuhiro Moriyama ◽  
Kana Matsumoto ◽  
Yasuyo Shimomura ◽  
Yu Kato ◽  
...  
Keyword(s):  
Adsorption Capacity ◽  
Antibacterial Agents ◽  
Kidney Injury ◽  
Control Group ◽  
Drug Bioavailability ◽  
Antibiotic Concentration ◽  
Sieving Coefficient ◽  
Drug Concentrations ◽  
Septic Acute Kidney Injury

Introduction: Renal replacement therapy (RRT) is widely used in the treatment of septic acute kidney injury. However, little is known about how the adsorption properties of hemofilters used in RRT affect antibiotic concentration. Because a cytokine-adsorption membrane is frequently used in RRT, it is important to determine the antibiotic adsorption capacity of this membrane. Objective: The present study aimed to investigate the antibiotic adsorption capacity of different hemofilter membranes by in vitro experiments using 2 antibacterial agents (linezolid and doripenem). Methods: We performed experimental hemofiltration in vitro using polyacrylonitrile (AN69ST), polymethylmethacrylate (PMMA), and polysulfone (PS) hemofilters for 1,440 min. The test solution was a 1,000-mL substitution fluid containing 30 µg/mL linezolid and 120 µg/mL doripenem. We measured drug concentrations at the inlet, outlet, and filtrate ports of the hemofilters for 1,440 min and calculated the sieving coefficient (SC) and adsorption rate (Ra) of the drugs onto the hemofilters. Results: The amount of linezolid adsorbed onto AN69ST, PMMA, and PS membranes was decreased relative to that in the control group at 15 min (p < 0.05). However, no SC for linezolid was obtained thereafter. The Ra of linezolid onto AN69ST, PMMA, and PS membranes was higher than that in the control group (p < 0.05). In contrast, no significant differences were observed in the concentrations and Ra values of doripenem adsorbed onto AN69ST, PMMA, and PS membranes compared with those in the control group. Conclusions: Doripenem was not adsorbed onto PMMA, PS, and AN69ST membranes. Linezolid was adsorbed onto PMMA, PS, and AN69ST membranes, but only temporarily, and this did not affect drug bioavailability.

scholarly journals RIP3 impedes transcription factor EB to suppress autophagic degradation in septic acute kidney injury

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Ruizhao Li ◽  
Xingchen Zhao ◽  
Shu Zhang ◽  
Wei Dong ◽  
Li Zhang ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Transcription Factor ◽  
Nuclear Translocation ◽  
Kidney Injury ◽  
Septic Acute Kidney Injury ◽  
Transcription Factor Eb ◽  
Autophagic Degradation ◽  
Lps Treatment

AbstractAutophagy is an important renal-protective mechanism in septic acute kidney injury (AKI). Receptor interacting protein kinase 3 (RIP3) has been implicated in the renal tubular injury and renal dysfunction during septic AKI. Here we investigated the role and mechanism of RIP3 on autophagy in septic AKI. We showed an activation of RIP3, accompanied by an accumulation of the autophagosome marker LC3II and the autophagic substrate p62, in the kidneys of lipopolysaccharide (LPS)-induced septic AKI mice and LPS-treated cultured renal proximal tubular epithelial cells (PTECs). The lysosome inhibitor did not further increase the levels of LCII or p62 in LPS-treated PTECs. Moreover, inhibition of RIP3 attenuated the aberrant accumulation of LC3II and p62 under LPS treatment in vivo and in vitro. By utilizing mCherry-GFP-LC3 autophagy reporter mice in vivo and PTECs overexpression mRFP-GFP-LC3 in vitro, we observed that inhibition of RIP3 restored the formation of autolysosomes and eliminated the accumulated autophagosomes under LPS treatment. These results indicated that RIP3 impaired autophagic degradation, contributing to the accumulation of autophagosomes. Mechanistically, the nuclear translocation of transcription factor EB (TFEB), a master regulator of the lysosome and autophagy pathway, was inhibited in LPS-induced mice and LPS-treated PTECs. Inhibition of RIP3 restored the nuclear translocation of TFEB in vivo and in vitro. Co-immunoprecipitation further showed an interaction of RIP3 and TFEB in LPS-treated PTECs. Also, the expression of LAMP1 and cathepsin B, two potential target genes of TFEB involved in lysosome function, were decreased under LPS treatment in vivo and in vitro, and this decrease was rescued by inhibiting RIP3. Finally, overexpression of TFEB restored the autophagic degradation in LPS-treated PTECs. Together, the present study has identified a pivotal role of RIP3 in suppressing autophagic degradation through impeding the TFEB-lysosome pathway in septic AKI, providing potential therapeutic targets for the prevention and treatment of septic AKI.

scholarly journals An Explanation of the Underlying Mechanisms for the In Vitro and In Vivo Antiurolithic Activity of Glechoma longituba

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Qiang Liang ◽  
Xiaoran Li ◽  
Wangning Zhou ◽  
Yu Su ◽  
Shenbao He ◽  
...  
Keyword(s):  
Kidney Injury ◽  
Positive Control ◽  
Potassium Citrate ◽  
Positive Control Group ◽  
Control Group ◽  
Protective Effects ◽  
In Vivo Models ◽  
Glechoma Longituba

Purpose. To use in vitro and in vivo models to evaluate Glechoma longituba extract to provide scientific evidence for this extract’s antiurolithic activity. Materials and Methods. Potassium citrate was used as a positive control group. Oxidative stress (OS) markers and the expression of osteopontin (OPN) and kidney injury molecule-1 (KIM-1) were measured to assess the protective effects of Glechoma longituba. Multiple urolithiasis-related biochemical parameters were evaluated in urine and serum. Kidneys were harvested for histological examination and the assessment of crystal deposits. Results. In vitro and in vivo experiments demonstrated that treatment with Glechoma longituba extract significantly decreased calcium oxalate- (CaOx-) induced OPN expression, KIM-1 expression, and OS compared with the positive control group (P<0.05). Additionally, in vivo rats that received Glechoma longituba extract exhibited significantly decreased CaOx deposits and pathological alterations (P<0.05) compared with urolithic rats. Significantly lower levels of oxalate, creatinine, and urea and increased citrate levels were observed among rats that received Glechoma longituba (P<0.05) compared with urolithic rats. Conclusion. Glechoma longituba has antiurolithic effects due to its possible combined effects of increasing antioxidant levels, decreasing urinary stone-forming constituents and urolithiasis-related protein expression, and elevating urinary citrate levels.

scholarly journals IL-17A activated by Toll-like receptor 9 contributes to the development of septic acute kidney injury

2020 ◽  
Vol 318 (1) ◽  
pp. F238-F247
Author(s):  
Yoshitaka Naito ◽  
Takayuki Tsuji ◽  
Soichiro Nagata ◽  
Naoko Tsuji ◽  
Tomoyuki Fujikura ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Critical Role ◽  
Cecal Ligation ◽  
Kidney Injury ◽  
Mrna Levels ◽  
Toll Like Receptor ◽  
Γδt Cells ◽  
Morphological Aspects ◽  
Septic Acute Kidney Injury

Toll-like receptor 9 (TLR9), which is activated by endogenously released mtDNA during sepsis, contributes to the development of polymicrobial septic acute kidney injury (AKI). However, downstream factors of TLR9 to AKI remain unknown. We hypothesized that IL-17A activated by TLR9 may play a critical role in septic AKI development. To determine the effects of TLR9 on IL-17A production in septic AKI, we used a cecal ligation and puncture (CLP) model in Tlr9 knockout ( Tlr9KO) mice and wild-type (WT) littermates. We also investigated the pathway from TLR9 activation in dendritic cells (DCs) to IL-17A production by γδT cells in vitro. To elucidate the effects of IL-17A on septic AKI, Il-17a knockout ( Il-17aKO) mice and WT littermates were subjected to CLP. We further investigated the relationship between the TLR9-IL-17A axis and septic AKI by intravenously administering recombinant IL-17A or vehicle into Tlr9KO mice and assessing kidney function. IL-17A levels in both plasma and the peritoneal cavity and mRNA levels of IL-23 in the spleen were significantly higher in WT mice after CLP than in Tlr9KO mice. Bone marrow-derived DCs activated by TLR9 induced IL-23 and consequently promoted IL-17A production in γδT cells in vitro. Knockout of Il-17a improved survival, functional and morphological aspects of AKI, and splenic apoptosis after CLP. Exogenous IL-17A administration aggravated CLP-induced AKI attenuated by knockout of Tlr9. TLR9 in DCs mediated IL-17A production in γδT cells during sepsis and contributed to the development of septic AKI.

The combined treatment of 150 kHz tumor treating fields (TTFields) and sorafenib inhibits hepatocellular carcinoma in vitro and in vivo.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15653-e15653 ◽  
Author(s):  
Uri Weinberg ◽  
Shiri Davidi ◽  
Catherine Tempel- Brami ◽  
Mijal Munster ◽  
Karnit Gotlib ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Combined Treatment ◽  
Control Group ◽  
Multikinase Inhibitor ◽  
Tumor Treating Fields ◽  
Cell Counts ◽  
Drug Concentrations ◽  
Clonogenic Potential ◽  
Hcc Cells

e15653 Background: Hepatocellular carcinoma (HCC) is the third cause of cancer related mortality and the primary cause of cancer death. Tumor Treating Fields (TTFields) therapy is an effective anti-neoplastic treatment modality delivered via noninvasive application of low intensity, intermediate frequency, alternating electric fields. Sorafenib, an oral multikinase inhibitor is approved for patients with advanced HCC, yet its survival benefit is still limited. In this work we explored the potential of the use of TTFields alone and in combination with Sorafenib as a treatment for HCC. Methods: HepG2 and Huh-7D12 cells were treated with various TTFields frequencies for 72 hours using the inovitro system. Efficacy of the combined treatment of TTFields and Sorafenib (36-3000 nM) was tested by applying TTFields at the optimal frequency together with various drug concentrations. Cell counts, induction of apoptosis, cell cycle and clonogenic potential were determined. TTFields (1.2 V/cm) and Sorafenib (10 mg/kg) were applied for 6 days to rats injected to the liver with N1S1 HCC cells. Tumor growth was followed using MRI. Results: The optimal TTFields frequency was 150 kHz for both cell lines. TTFields application (1.0 - 1.7 V/cm, 72 hours) at 150 kHz led to 36-40% reduction in cell counts and to additional reduction of over 70% in the clonogenic potential. The combined treatment of TTFields and Sorafenib led to a significant reduction in the number of cells (p < 0.001) as compared to each treatment alone. The averaged tumor volume fold increase of the combination treatment group was significantly lower than the one observed in the: control group, the TTFields group and the Sorafenib group. Conclusions: The results presented in this work demonstrate that TTFields can be an effective treatment against HCC cells and that the combination with Sorafenib may further enhance treatment efficacy.

Abstract 325: Brain Natriuretic Peptide During Coronary Intervention Prevents Endothelial Dysfunction Post PCI via NP-cGMP Activation

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Aviva Peleg ◽  
Yonathan Hasin
Keyword(s):  
Endothelial Dysfunction ◽  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Kidney Injury ◽  
Coronary Intervention ◽  
Control Group ◽  
Estimate Glomerular Filtration Rate ◽  
And Control

Background: Contrast media (CM) administrated during percutaneous coronary intervention (PCI) is associated with endothelial dysfunction (ED) and systemic vascular injury. Brain natriuretic peptide (BNP) administration 24 hours post PCI decreases ED. Aims: To evaluate 1.The ability of human BNP (hBNP) infusion during PCI, to prevent ED in acute coronary syndrome's (ACS) patients post the PCI. 2. The effect of CM on human coronary microvascular endothelial cells (HCMEC).3. Explain ED by invitro study. Methods and results (in vivo): Non-ST elevation ACS patients who underwent PCI (111) were randomized into 2 groups: an hBNP group who received hBNP infusion during the procedure (n=44), and control group who received nitroglycerin (n=67). Flow mediated dilatation (FMD) (by ≥2.5%), BNP, corin, serum creatinine (sCr) and estimate Glomerular Filtration Rate (eGFR), before and 24 hr after operative were recorded, starting with the same baseline. The post PCI FMD and eGFR were significantly reduced in the control group (p=0.05, 0.002) but not in the hBNP group (p=0.16, 0.4). BNP, corin and sCr increased significantly in the control group (p=0.001, 0.003, 0.0002 respectively) but not in hBNP group (p=0.09, 0.07, 0.18). Methods and results (in vitro): HCMEC were treated with CM (10%) in the presence and absence of BNP. eNOS, corin and cGMP levels were measured by ELISA and the results were compared to untreated cells. In both treatments eNOS was significantly reduced (p=0.001) and corin was significantly increased (p=0.002). cGMP was not affected by CM treatment (p=0.278), but was increased significantly (p=0.001) by hBNP combination. cGMP immuno-flourescence staining of HCMEC showed distorted cellular cGMP appearance by CM treatment, that was corrected in the combination with hBNP with accentuated subsarcolemmal staining. Conclusions: CM reduces eNOS level in HCMEC. Therefore, reduced in NO-cGMP pathway's products, probably is the mechanism that induces ED in-vivo. BNP treatment reduces FMD diminution and kidney injury post PCI. A compensatory rise in corin that increases BNP as well as the hBNP administration, invivo and invitro, maintains cytosolic cGMP via NP-cGMP pathway, and compensates for NO-cGMP loss, (reduced sGC) and thus prevents ED.

scholarly journals Isoliquiritigenin attenuates LPS-induced acute kidney injury through suppression of HMGB1 pathway in renal tubular against ferritinophagy

2020 ◽  
Author(s):  
Yun Tang ◽  
Yanmei Wang ◽  
Chan Wang ◽  
Meidie Yu ◽  
Li Li ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Renal Dysfunction ◽  
Kidney Injury ◽  
Tubular Injury ◽  
Renal Tubular Cells ◽  
Septic Acute Kidney Injury ◽  
Life Threatening ◽  
Renal Tubular

Abstract Septic acute kidney injury (AKI) mainly results in life-threatening renal dysfunction involving renal tubular injury to bring heavy burden to patients in intensive care unit (ICU). However, there is still a lack of therapy to prevent septic AKI effectively and inexpensive. To observe the role and novel mechanism of isoliquiritigenin (ISL) which isolated from the roots of licorice in septic AKI, we used LPS to induce renal tubular injury upon septic AKI both in vitro and in vivo. 50mg/kg ISL and 5 mg/kg Ferrostatin-1 were once given to the male C57BL/6 mice one hour before 1 mg/kg LPS i.p injection. 50 μM and 100 μM ISL respectively pre-treat the human renal tubular cells 5 hrs before 2 μg/ml LPS stimulation. We found ISL pretreatment apparently reversed LPS-induced renal dysfunction and ameliorated murine renal tubular injury by suppression HMGB1 pathway. Furthermore, we observed that LPS induced autophagy and ferroptosis in renal tubular, whereas ISL pretreatment significantly suppress autophagy and ferroptosis of renal tubular both in vitro and in vivo. Mechanically, autophagy activated ferroptosis via NCOA4-mediated ferritinophagy. Moreover, HMGB1 is required for ferritinophagy in renal tubular. ISL treatment inhibited the expression of HMGB1. Taken together, these results suggest that ISL protects LPS-induced acute kidney injury through suppression of HMGB1 pathway in renal tubular against ferritinophagy.

P0532CD8+CD103+ INDUCED REGULATORY T CELLS BUT NOT NATURE REGULATORY T CELLS AMELIORATE IR-INDUCED KIDNEY INJURY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Tongtong Xu ◽  
Zhenjian Xu ◽  
Liling Chen ◽  
Anping Xu
Keyword(s):  
T Cells ◽  
Body Weight ◽  
Treatment Group ◽  
Regulatory T Cells ◽  
Inflammatory Response ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Control Group ◽  
O2 Concentration

Abstract Background and Aims Acute kidney injury (AKI) is one of the most common complications in clinical practice, but current approaches offer no cures for AKI. Inflammatory response is the key mechanism of ischemia reperfusion (IR)-induce AKI, known as hypoxia/reoxygenation injury. T lmphocytes are crucial mediators of IR-induced AKI. It is reported that regulatory T cell (Treg) has potential ability to ameliorate IR-induced AKI. Tregs consist of nature Treg (nTreg) and induced Treg (iTreg), which are well established to blunt immune responses. We confirmed that CD8+CD103+iTreg remain steadily and barely transfer into Th17, which produce proinflammatory response, under inflammatory response. It is studied that nTreg tends to transfer into Th17 under inflammatory condition, which clarifies the instability of nTreg. Thus, the instability of nTreg under inflammatory response hints us that nTreg are not suitable for recovery from IR-induced AKI. Accordingly, we studied the role of CD8+CD103+iTreg in repair after IR-induced kidney. Method In vitro study, we test the expression of CD103, Foxp3 and IL-17a in CD8+CD103+iTreg under 1% O2 concentration. In vivo study, SPF C57BL/6J male mice (8-10 weeks old, body weight 20-25g) were divided into four groups, sham-operated control group, AKI group, iTreg treatment group and nTreg treatment group, with 6 mice in each group. On the day of surgery, we anesthetize the mice (pen-tobarbital sodium, 50 mg/kg body weight). Mice in the AKI group were reperfused after 25 minutes of bilateral renal artery ischemia. We injected CD8+CD103+iTreg (2 × 106/mouse) or nTreg (2 × 106/mouse) intraperitoneally after 24 hours of modeling to the treatment group and euthanized the mice on the third day of anesthesia. Results We discovered that the expression of CD103 is stable in CD8+iTreg in vitro under 1% O2 concentration (Figure 1, 2). In addition, their inhibiting abilities of T cells proliferation in vitro remain steadily (Figure not shown). However, CD8+CD103+iTreg seldom transfer into Th17, but remain Foxp3 under hypoxic condition (Figure 2). Adoptively transferring CD8+CD103+iTregs, a new subpopulation of CD8+iTreg we have identified, to AKI mice, we found that these cells can ameliorate the development of AKI by mitigating the level of serum creatine, alleviating acute tubular necrosis (ATN) and decreasing the mortality of AKI. Conclusion Therefore, we confirmed that CD8+CD103+iTreg is stable under inflammatory(hypoxic) environment. Thus, CD8+CD103+iTreg targeting may be a novel therapeutic approach to enhance recovery from IR-induced AKI.

scholarly journals Melittin Inducing the Apoptosis of Renal Tubule Epithelial Cells through Upregulation of Bax/Bcl-2 Expression and Activation of TNF-α Signaling Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Ying Shu ◽  
Yingying Yang ◽  
Yuliang Zhao ◽  
Liang Ma ◽  
Ping Fu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Signaling Pathway ◽  
Kidney Injury ◽  
Protein Detection ◽  
Severe Illness ◽  
Control Group ◽  
Mrna Levels ◽  
Tail Vein

Background. Acute kidney injury (AKI) caused by bee stings is common, with characteristics of acute onset, severe illness, and high mortality. Melittin, a major component of bee venom, has been considered to play a key role in bee sting related AKI. This study aims to illustrate whether melittin could lead to apoptosis of renal tubular epithelial cells (RTECs) and to investigate its mechanism. Methods. In vivo, 45 mice were randomly divided into the melittin group (n=30, injected with melittin into the tail vein according to the total dose of 4.0 ug/g weight) and the control group (n=15, injected with the same volume of saline into the tail vein). In vitro, human RTECs (HK-2) were cultured and treated with melittin (2ug/ml or 4ug/ml) and TNF-α (10ng/ml). Biochemical analysis, HE stains, and electron microscope were performed to evaluate renal function and pathological changes. TUNEL stains and flow cytometry were performed to detect apoptosis. Real-time PCR was performed to detect mRNA levels of Bax, Bcl-2, and TNF-α. Simple western assay and immunohistochemical (IH) and immunofluorescent (IF) stains were performed for protein detection. Results. Melittin successfully induced AKI in mice. Compared with the control group, obvious injury and apoptosis of RTECs were observed in the melittin group; the mRNA and protein expressions of Bax were significantly increased, while the expression of Bcl-2 was significantly decreased. The serum TNF-αlevel in melittin group was significantly higher than that in control group. In vitro, the results confirmed that melittin can cause HK-2 cells apoptosis. The trends of expression of Bax and Bcl-2 were consistent with the results in vivo. The levels of TNF-α mRNA and protein by PCR and Western blot were significantly higher in melittin group than those in control group. Conclusion. Melittin can lead to the apoptosis of RTECs, which may be mediated by upregulating the expression of Bax/Bcl-2 and activating the TNF-α signaling pathway.

scholarly journals 127 LETHAL EFFECT OF HIGH CONCENTRATIONS OF PARECOXIB AND FLUNIXIN MEGLUMINE ON THE IN VITRO CULTURE OF BOVINE EMBRYOS

2009 ◽  
Vol 21 (1) ◽  
pp. 163 ◽  
Author(s):  
E. M. Razza ◽  
R. A. Satrapa ◽  
C. F. Silva ◽  
R. A. L. Simões ◽  
T. Nabhan ◽  
...  
Keyword(s):  
Cumulus Cells ◽  
Lethal Effect ◽  
Control Group ◽  
Published Data ◽  
Bovine Embryo ◽  
Bovine Embryos ◽  
Flunixin Meglumine ◽  
Plastic Bags ◽  
Drug Concentrations

The aim of this experiment was to evaluate the effects of cycloxigenase inhibitor drugs, i.e. flunixin meglumine (FM) and parecoxib (P), on the development of bovine embryos cultured in vitro until the blastocyst and hatched blastocyst stages. Immature oocytes were aspirated from slaughterhouse ovaries and morphologically selected for IVM (Monteiro FM et al. 2007 Anim. Reprod. 4, 51–58). Twenty hours after maturation (39°C and 5% CO2 in air), matured oocytes were transferred to fertilization media, inseminated with frozen–thawed semen, and incubated for 10 to 12 h. Presumptive zygotes (PZ) were then transferred to TCM 199 HEPES medium, vortexed to remove cumulus cells and finally to drops of IVC media (SOFaaci plus 5% BFS [Gibco] with 13 mm sodium pyruvate). Each drop of IVC medium had appropriate concentrations of FM (0.14/n = 123; 1.4/n = 122; 14/n = 117; 140/n = 44 or 1400 μg mL–1/n = 44 PZ) or P (0.09/n = 134; 0.9/n = 109; 9/n = 118; 90/n = 113 or 900 μg mL–1/n = 45 PZ), besides extra drops as control groups (CFM; n = 124 and CP; n = 149 PZ). Based on published data from bovine (FM) and human (P) administered concentrations, it was calculated the blood concentration to a bovine weighing 450 kg (FM = 14 and P = 9 μg mL–1). Both drugs were used from available commercial preparations, and in a pilot test, there were no deleterious effects of the solvent itself on the blastocyst and hatched blastocyst rates. During culture, petri dishes containing PZ/embryos were kept into plastic bags, under controlled atmosphere of 5% O2, 5% CO2 and 90% N2 at 39°C. There were 11 replicates for each treatment. In all drops (both drug concentrations and control group) the blastocyst and hatched blastocyst rates (BR and HBR, respectively) were evaluated at 144 and 192 h after fertilization, respectively. Statistical analysis was performed with ANOVA on ranks (Dunn’s test a posteriori and significance being considered when P < 0.05; BioEstat version 5.0). According to the results, FM (1400 and 140 μg mL–1) and P (900 μg mL–1) concentrations were toxic enough for a complete inhibition of in vitro bovine embryo development. There were no significant differences among the other drug concentrations and their respective control group, on the BR (27.7 ± 3.9; 29.6 ± 3.4 and 29.8% ± 4.8) and HBR (13.5 ± 4.4; 15.6 ± 3.8 and 22.1% ± 5.1), respectively to 0.14; 1.4 and 14 μg mL–1 for FM; on BR (26.0 ± 2.6; 18.2 ± 4.6; 25.8 ± 5.9 and 23.2% ± 4.8) and HBR (14.1 ± 3.3; 10.2 ± 3.3; 16.8 ± 3.8 and 12.0% ± 3.4), respectively to 0.09; 0.9; 9 and 90 μg mL–1 for P; and on BR (35.3 ± 5.2 and 36.5% ± 3.4) and HBR (26.6 ± 4.5 and 19.8% ± 3.6), respectively for CFM and CP. The results suggest that, during in vitro bovine embryo culture, there was no significant toxicity of either drug, with exception of the complete lethal concentrations of 140 and 1400 μg mL–1 (flunixin meglumine) and 900 μg mL–1 (parecoxib) on blastocyst production. Supported by FAPESP – Brazil (MFGN 06/06491-2 and 07/07705-9; EMR 07/04284-2; RAS; CFS and RALS) and CAPES – Brazil.

scholarly journals LncRNA-UCA1 Alleviates Septic Acute Kidney Injury through Regulating Endoplasmic Reticulum Stress in LPS-treated HK-2 Cells

2021 ◽  
Author(s):  
TT Yu ◽  
FL Cai ◽  
J Niu
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Noncoding Rna ◽  
Kidney Injury ◽  
Tunel Staining ◽  
Septic Acute Kidney Injury ◽  
Commercial Kits

AbstractObjectiveSeptic acute kidney injury (AKI) is an important cause of death in patients with sepsis. This study sought to explore the function of the long noncoding RNA, urothelial carcinoma associated 1 (lncRNA-UCA1), in septic AKI and determine the underlying molecular mechanism.MethodsHK-2 cells were treated with lipopolysaccharide (LPS) to establish an in vitro model of septic AKI. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was used to detect the expression of lncRNA-UCA1. CCK-8 assay was used to detect the viability of HK-2 cells. Western blotting was utilized to examine protein expression. The contents of SOD, GSH, MDA, and ROS were determined using commercial kits. The apoptosis rate was calculated using TUNEL staining and flow cytometry.ResultsLncRNA-UCA1 was down-regulated in LPS-treated HK-2 cells. LPS significantly reduced the content of SOD and GSH in HK-2 cells, increased the production of MDA and ROS, and led to an increase in the rate of apoptosis. However, overexpression of lncRNA-UCA1 protected HK-2 cells from oxidative stress and apoptosis. Furthermore, LPS induced endoplasmic reticulum (ER) stress in HK-2 cells, which was inhibited by overexpression of lncRNA-UCA1.ConclusionOverexpression of lncRNA-UCA1 inhibited LPS-induced oxidative stress and apoptosis of HK-2 cells by suppressing ER stress.

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