Taurine alleviates kidney injury in a thioacetamide rat model by mediating Nrf2/HO-1, NQO-1 and MAPK/ NF-κB signaling pathways

2021 ◽  
Author(s):  
Amal Ghanim ◽  
Mahmoud Farag ◽  
Mahitab Anwar ◽  
Nada Ali ◽  
Mohammed Hawas ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Kidney Injury ◽  
Mapk Signaling ◽  
Significant Rise ◽  
Protective Effects ◽  
Gene Expressions ◽  
Protein Levels ◽  
Taurine Treatment ◽  
Anti Oxidant ◽  
Anti Inflammatory

Abstract: This study aimed to investigate the molecular mechanisms by which taurine exerts its reno-protective effects in thioacetamide (TAA)-induced kidney injury in rats. Rats received taurine (100 mg/kg daily, intraperitoneally) either from day 1 of TAA injection (250 mg/kg twice weekly for 6 weeks) or after 6 weeks of TAA administration. Taurine treatment, either concomitant or later as a therapy, restored kidney functions, reduced BUN, creatinine, MDA, and increased renal levels of SOD and reversed the increase of KIM-1 and NGAL caused by TAA. Taurine treatment also led to a significant rise in Nrf2, HO-1, and NQO-1 levels, with significant suppression of ERK 1/2, NF-κB, and TNFα gene expressions, and IL-18 and TNFα protein levels compared to those in TAA kidney-injured rats. Taurine exhibited reno-protective potential in TAA-induced kidney injury through its anti-oxidant and anti-inflammatory effects. Taurine anti-oxidant activity is accredited to its effect on Nrf-2 induction and subsequent activation of HO-1 and NQO-1. In addition, taurine exerts its anti-inflammatory effect via regulating NF-κB transcription and subsequent production of pro-inflammatory mediators via MAPK signaling regulation.

scholarly journals Anti-Oxidant and Anti-Inflammatory Effects of Lipopolysaccharide from Rhodobacter sphaeroides against Ethanol-Induced Liver and Kidney Toxicity in Experimental Rats

Molecules ◽  
2021 ◽  
Vol 26 (24) ◽  
pp. 7437
Author(s):  
Eman T. Mehanna ◽  
Al-Shimaa A. Ali ◽  
Fatma El-Shaarawy ◽  
Noha M. Mesbah ◽  
Dina M. Abo-Elmatty ◽  
...  
Keyword(s):  
Rhodobacter Sphaeroides ◽  
Iron Homeostasis ◽  
Kidney Injury ◽  
Control Group ◽  
Protective Effects ◽  
Necrosis Factor Alpha ◽  
Hepcidin Expression ◽  
Tnf Α ◽  
Anti Oxidant ◽  
Anti Inflammatory

This study aimed to investigate the protective effects of lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS) against ethanol-induced hepatotoxicity and nephrotoxicity in experimental rats. The study involved an intact control group, LPS-RS group, two groups were given ethanol (3 and 5 g/kg/day) for 28 days, and two other groups (LPS-RS + 3 g/kg ethanol) and (LPS-RS + 5 g/kg ethanol) received a daily dose of LPS-RS (800 μg/kg) before ethanol. Ethanol significantly increased the expression of nuclear factor kappa B (NF-κB) and levels of malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in the liver tissue and decreased anti-oxidant enzymes. Hepcidin expression was downregulated in the liver, with increased serum levels of ferritin and iron. Prior-administration of LPS-RS alleviated the increase in oxidative stress and inflammatory markers, and preserved iron homeostasis markers. In the kidney, administration of ethanol caused significant increase in the expression of NF-κB and the levels of TNF-α and kidney injury markers; whereas LPS-RS + ethanol groups had significantly lower levels of those parameters. In conclusion; this study reports anti-oxidant, anti-inflammatory and iron homeostasis regulatory effects of the toll-like receptor 4 (TLR4) antagonist LPS-RS against ethanol induced toxicity in both the liver and the kidney of experimental rats.

scholarly journals Benzoylaconine Modulates LPS-Induced Responses through Inhibition of Toll-Like Receptor-Mediated NF-κB and MAPK Signaling in RAW264.7 Cells

2021 ◽  
Author(s):  
Changkai Zhou ◽  
Jing Gao ◽  
Hongyan Ji ◽  
Wenjing Li ◽  
Xiaomin Xing ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Nuclear Translocation ◽  
Mapk Signaling ◽  
Dependent Manner ◽  
Toll Like Receptor ◽  
Protein Levels ◽  
Raw264.7 Macrophages ◽  
Elevated Protein ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Abstract Previous studies have shown that benzoylaconine (BAC), a representative monoester alkaloid, has a potential anti-inflammatory effect. This study investigated the underlying molecular mechanisms using the mode of LPS-activated RAW264.7 macrophage cells. Our findings showed that BAC significantly suppressed the release of pro-inflammatory cytokines and mediators, including IL-6, TNF-α, IL-1β, ROS, NO, and PGE2. BAC treatment also effectively downregulated the elevated protein levels of iNOS and COX-2 induced by LPS in a dose-dependent manner. In this study, we found that BAC inhibited LPS-induced NF-κB activation by reducing the phosphorylation and degradation of IκBα by Western blotting and blocking the nuclear translocation of p65 using an immunofluorescence assay. The elevated protein levels of JNK, p38, and ERK phosphorylation after LPS stimulation were restored effectively by BAC treatment. Moreover, LPS-induced phosphorylation of TAK1, which is a crucial upstream regulatory factor of Toll-like receptor-induced MAPK and NF-κB signaling, was inhibited by BAC in activated RAW264.7 macrophages. These findings demonstrated that BAC exhibited an anti-inflammatory effect by inhibition of Toll-like receptor-induced MAPK and NF-κB pathways, indicating that it could potentially be used for treating inflammatory diseases.

Early ghrelin intervention protects against the progressive dopaminergic neuron loss in Parkinson’s disease mice

2020 ◽  
Author(s):  
Lingling Jiao ◽  
Fengju Jia ◽  
Xixun Du ◽  
Pei Zhang ◽  
Yong Li ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Weight Loss ◽  
Parkinson's Disease ◽  
Inflammatory Cytokine ◽  
Protective Factor ◽  
Subcutaneous Administration ◽  
Protein Levels ◽  
Potential Applications ◽  
Anti Oxidant ◽  
Anti Inflammatory

Abstract BackgroundGhrelin has been identified as a multifunctional peptide that has many potential applications for the treatment of various diseases, including Parkinson’s disease (PD). However, little is known about the pathophysiological function and mechanism of ghrelin in PD. MethodELISA was used for detecting plasma total and active ghrelin levels, dopamine (DA) content was measured by HPLC-ECD, immunofluorescence staining and Western blot were used to detect protein expressions, and cytokine was tested by Bio-PlexPro™ assay.ResultsHere, we reported a PD model that overexpressing mutant human A53T α-syn mice exhibited a decreased levels of total and active ghrelin in plasma, fewer tyrosine hydroxylase (TH)-positive neurons in the substantia nigra (SN), lower DA content in the striatum (Str), and less weight. These changes were rescued by the subcutaneous administration of low-dose ghrelin. Interestingly, ghrelin had no effect on weight gain in wild-type mice but improved weight loss in A53T mice. In addition, ghrelin administration also attenuated the decreased Bcl-2/Bax ratio and superoxide dismutase1 (SOD1) protein levels and inhibited the upregulation pro-inflammatory cytokine interleukin-6 (IL-6) and tumour necrosis factor a (TNFa) and the downregulation of anti-inflammatory cytokine IL-10. In addition, ghrelin inhibited the increase in Iba1-positive cells in mice with PD.ConclusionsHere we reported that ghrelin had a protective effect on dopaminergic neurons and against weight loss from PD via anti-oxidant, anti-inflammatory and anti-apoptotic mechanisms, which suggested that ghrelin could be an endogenous protective factor that prevents the onset or the progression of PD.

Anti-Apoptotic and Anti-Inflammatory Activities of Edible Fresh Water Algae Prasiola japonica in UVB-Irradiated Skin Keratinocytes

2019 ◽  
Vol 47 (08) ◽  
pp. 1853-1868
Author(s):  
Eunju Choi ◽  
Young-Su Yi ◽  
Jongsung Lee ◽  
Sang Hee Park ◽  
Sunggyu Kim ◽  
...  
Keyword(s):  
Fresh Water ◽  
Ethanol Extract ◽  
The Body ◽  
Hacat Cells ◽  
Protective Effects ◽  
Proteolytic Activation ◽  
Skin Keratinocytes ◽  
External Stresses ◽  
Anti Oxidant ◽  
Anti Inflammatory

Skin is the outer tissue layer and is a barrier protecting the body from various external stresses. The fresh water green edible algae Prasiola japonica has antiviral, antimicrobial, and anti-inflammatory properties; however, few studies of its effects on skin-protection have been reported. In this study, Prasiola japonica ethanol extract (Pj-EE) was prepared, and its skin-protective properties were investigated in skin keratinocytes. Pj-EE inhibited ROS production in UVB-irradiated HaCaT cells without cytotoxicity. Pj-EE also suppressed the apoptotic death of UVB-irradiated HaCaT cells by decreasing the generation of apoptotic bodies and the proteolytic activation of apoptosis caspase-3, -8, and -9. Moreover, Pj-EE downregulated the mRNA expression of the inflammatory gene cyclooxygenase-2 (COX-2), the pro-inflammatory cytokine genes interleukin (IL)-1[Formula: see text], IL-8, IL-6, tumor necrosis factor (TNF)-[Formula: see text], and interferon (IFN)-[Formula: see text], and the tissue remodeling genes matrix metalloproteinase (MMP)-1, -2, -3, and -9. The Pj-EE-induced anti-inflammatory effect was mediated by suppressing the activation of nuclear factor-kappa B (NF-[Formula: see text]B) signaling pathway in the UVB-irradiated HaCaT cells. Taken together, these results suggest that Pj-EE exerts skin-protective effects through anti-oxidant, anti-apoptotic, and anti-inflammatory activities in skin keratinocytes.

Sageretia thea Inhibits Inflammation through Suppression of NF-κB and MAPK and Activation of Nrf2/HO-1 Signaling Pathways in RAW264.7 Cells

2019 ◽  
Vol 47 (02) ◽  
pp. 385-403 ◽  
Author(s):  
Ha Na Kim ◽  
Gwang Hun Park ◽  
Su Bin Park ◽  
Jeong Dong Kim ◽  
Hyun Ji Eo ◽  
...  
Keyword(s):  
Inhibitory Effect ◽  
Mapk Signaling ◽  
Inflammatory Activity ◽  
Nuclear Accumulation ◽  
Raw264.7 Cells ◽  
No Production ◽  
Immunodeficiency Virus ◽  
Anti Oxidant ◽  
Anti Inflammatory ◽  
Signaling Activation

Sageretia thea (S. thea) commonly known as Chinese sweet plum or Chinese bird plum has been used for treating hepatitis and fevers in Korea and China. S. thea has been reported to exert anti-oxidant, anticancer and anti-human immunodeficiency virus activity. However, there is little study on the anti-inflammatory activity of S. thea. Thus, we evaluated the anti-inflammatory effect of extracts of leaves (ST-L) and branches (ST-B) from Sageretia thea in LPS-stimulated RAW264.7 cells. ST-L and ST-B significantly inhibited the production of the pro-inflammatory mediators such as NO, iNOS, COX-2, IL-1[Formula: see text] and IL-6 in LPS-stimulated RAW264.7 cells. ST-L and ST-B blocked LPS-induced degradation of I[Formula: see text]B-[Formula: see text] and nuclear accumulation of p65, which resulted in the inhibition of NF-[Formula: see text]B activation in RAW264.7 cells. ST-L and ST-B also attenuated the phosphorylation of ERK1/2, p38 and JNK in LPS-stimulated RAW264.7 cells. In addition, ST-L and ST-B increased HO-1 expression in RAW264.7 cells, and the inhibition of HO-1 by ZnPP reduced the inhibitory effect of ST-L and ST-B against LPS-induced NO production in RAW264.7 cells. Inhibition of p38 activation and ROS elimination attenuated HO-1 expression by ST-L and ST-B, and ROS elimination inhibited p38 activation induced by ST-L and ST-B. ST-L and ST-B dramatically induced nuclear accumulation of Nrf2, but this was significantly reversed by the inhibition of p38 activation and ROS elimination. Collectively, our results suggest that ST-L and ST-B exerts potential anti-inflammatory activity by suppressing NF-[Formula: see text]B and MAPK signaling activation, and activating HO-1 expression through the nuclear accumulation of Nrf2 via ROS-dependent p38 activation. These findings suggest that ST-L and ST-B may have great potential for the development of anti-inflammatory drug to treat acute and chronic inflammatory disorders.

Berberine inhibits lipopolysaccharide-induced expression of inflammatory cytokines by suppressing TLR4-mediated NF-ĸB and MAPK signaling pathways in rumen epithelial cells of Holstein calves

2019 ◽  
Vol 86 (2) ◽  
pp. 171-176 ◽  
Author(s):  
Chenxu Zhao ◽  
Yazhou Wang ◽  
Xue Yuan ◽  
Guoquan Sun ◽  
Bingyu Shen ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Signaling Pathways ◽  
Inflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Mapk Signaling ◽  
Dependent Manner ◽  
Inflammatory Drug ◽  
Anti Inflammatory ◽  
Mapk Signaling Pathways ◽  
Rumen Epithelial Cells

AbstractSubacute ruminal acidosis (SARA) can increase the level of inflammation and induce rumenitis in dairy cows. Berberine (BBR) is the major active component of Rhizoma Coptidis, which is a type of Chinese anti-inflammatory drug for gastrointestinal diseases. The purpose of this study was to investigate the anti-inflammatory effects of BBR on lipopolysaccharide (LPS)-stimulated rumen epithelial cells (REC) and the underlying molecular mechanisms. REC were cultured and stimulated with LPS in the presence or absence of different concentrations of BBR. The results showed that cell viability was not affected by BBR. Moreover, BBR markedly decreased the concentrations and mRNA expression of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, and interleukin-6 in the LPS-treated REC in a dose-dependent manner. Importantly, Western blotting analysis showed that BBR significantly suppressed the protein expression of toll-like receptor 4 (TLR4) and myeloid differentiation primary response protein (MyD88) and the phosphorylation of nuclear factor-κB (NF-κB), inhibitory kappa B (IκBα), p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK) in LPS-treated REC. Furthermore, the results of immunocytofluorescence showed that BBR significantly inhibited the nuclear translocation of NF-κB p65 induced by LPS treatment. In conclusion, the protective effects of BBR on LPS-induced inflammatory responses in REC may be due to its ability to suppress the TLR4-mediated NF-κB and MAPK signaling pathways. These findings suggest that BBR can be used as an anti-inflammatory drug to treat inflammation induced by SARA.

scholarly journals Endoplasmic Reticulum Stress Is Involved in Baicalin Protection on Chondrocytes From Patients With Osteoarthritis

Dose-Response ◽  
2018 ◽  
Vol 16 (4) ◽  
pp. 155932581881063 ◽  
Author(s):  
Jiangang Cao ◽  
Yu Zhang ◽  
Tianyi Wang ◽  
Bo Li
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Cell Viability ◽  
Er Stress ◽  
Messenger Rna ◽  
Cell Counting ◽  
Protective Effects ◽  
Gene Expressions ◽  
Protein Levels

Osteoarthritis (OA) affects elderly population worldwide and endoplasmic reticulum (ER) stress is known to be positively correlated with OA development. Previous reports prove the cytoprotective effects of baicalin on chondrocytes, whereas the mechanisms are hardly reported. Hence, we aimed to investigate the links between OA, ER stress, and baicalin. Chondrocytes from patients with OA were subjected to H2O2 treatment with or without baicalin pretreatment, and cell viability was assessed via Cell Counting Kit-8. Messenger RNA (mRNA) amounts of apoptosis-related genes (Bax, Bcl-2, and Caspase-3), extracellular matrix (ECM)-related genes (Collange I, Collange II, Aggrecan, and Sox9) and ER stress hallmarks (binding immunoglobulin protein [BiP] C/EBP homologous protein [CHOP]) were evaluated via quantitative real-time PCR. Bax, Bcl-2, BiP, and CHOP protein levels were analyzed via Western blot. Baicalin suppressed the changes in cell viability and apoptosis-related gene expressions caused by H2O2. Reactive oxygen species and glutathione/oxidized glutathione assay showed that H2O2 enhanced oxidative stress. Baicalin suppressed H2O2-induced downregulation of mRNA expression of ECM-related genes. Moreover, baicalin reduced H2O2-stimulated increase in oxidative stress and the expression of ER stress hallmarks. Endoplasmic reticulum stress inducer abolished the protective activities, whereas ER stress inhibitor did not exhibit extra protective effects. Baicalin pretreatment protected patient-derived chondrocytes from H2O2 through ER stress inhibition.

scholarly journals TRAF3 Modulation: Novel Mechanism for the Anti-inflammatory Effects of the Vitamin D Receptor Agonist Paricalcitol in Renal Disease

2020 ◽  
Vol 31 (9) ◽  
pp. 2026-2042 ◽  
Author(s):  
Sandra Rayego-Mateos ◽  
Jose Luis Morgado-Pascual ◽  
José Manuel Valdivielso ◽  
Ana Belén Sanz ◽  
Enrique Bosch-Panadero ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Cultured Cells ◽  
Kidney Injury ◽  
Preclinical Model ◽  
Protein Levels ◽  
Inflammatory State ◽  
Anti Inflammatory ◽  
Injury Models ◽  
Inflammatory Effect

BackgroundCKD leads to vitamin D deficiency. Treatment with vitamin D receptor agonists (VDRAs) may have nephroprotective and anti-inflammatory actions, but their mechanisms of action are poorly understood.MethodsModulation of the noncanonical NF-κB2 pathway and its component TNF receptor–associated factor 3 (TRAF3) by the VDRA paricalcitol was studied in PBMCs from patients with ESKD, cytokine-stimulated cells, and preclinical kidney injury models.ResultsIn PBMCs isolated from patients with ESKD, TRAF3 protein levels were lower than in healthy controls. This finding was associated with evidence of noncanonical NF-κB2 activation and a proinflammatory state. However, PBMCs from patients with ESKD treated with paricalcitol did not exhibit these features. Experiments in cultured cells confirmed the link between TRAF3 and NF-κB2/inflammation. Decreased TRAF3 ubiquitination in K48-linked chains and cIAP1-TRAF3 interaction mediated the mechanisms of paricalcitol action.TRAF3 overexpression by CRISPR/Cas9 technology mimicked VDRA’s effects. In a preclinical model of kidney injury, paricalcitol inhibited renal NF-κB2 activation and decreased renal inflammation. In VDR knockout mice with renal injury, paricalcitol prevented TRAF3 downregulation and NF-κB2–dependent gene upregulation, suggesting a VDR-independent anti-inflammatory effect of paricalcitol.ConclusionsThese data suggest the anti-inflammatory actions of paricalcitol depend on TRAF3 modulation and subsequent inhibition of the noncanonical NF-κB2 pathway, identifying a novel mechanism for VDRA’s effects. Circulating TRAF3 levels could be a biomarker of renal damage associated with the inflammatory state.

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