Laminaria japonica fucoidan ameliorates cyclophosphamide‐induced liver and kidney injury possibly by regulating Nrf2/ HO ‐1 and TLR4 / NF‐κB signaling pathways

2021 ◽  
Author(s):  
Shanshan Tian ◽  
Xiaoxia Jiang ◽  
Yunping Tang ◽  
Tao Han
Keyword(s):  
Signaling Pathways ◽  
Kidney Injury ◽  
Laminaria Japonica ◽  
Liver And Kidney

scholarly journals Mesoporous Silica Nanoparticles Trigger Liver and Kidney Injury and Fibrosis Via Altering TLR4/NF-κB, JAK2/STAT3 and Nrf2/HO-1 Signaling in Rats

Biomolecules ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 528 ◽  
Author(s):  
Ayman M. Mahmoud ◽  
Ekram M. Desouky ◽  
Walaa G. Hozayen ◽  
May Bin-Jumah ◽  
El-Shaymaa El-Nahass ◽  
...  
Keyword(s):  
Mesoporous Silica ◽  
Silica Nanoparticles ◽  
Signaling Pathways ◽  
Mesoporous Silica Nanoparticles ◽  
Kidney Injury ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Liver And Kidney

Mesoporous silica nanoparticles (MSNs) represent a promising inorganic platform for multiple biomedical applications. Previous studies have reported MSNs-induced hepatic and renal toxicity; however, the toxic mechanism remains unclear. This study aimed to investigate MSNs-induced hepatic and nephrotoxicity and test the hypothesis that altered TLR4/MyD88/NF-κB, JAK2/STAT3, and Nrf2/ARE/HO-1 signaling pathways mediate oxidative stress, inflammation, and fibrosis induced by MSNs. Rats were administered 25, 50, 100, and 200 mg/kg MSNs for 30 days, and samples were collected for analyses. MSNs induced functional and histologic alterations, increased the levels of reactive oxygen species (ROS), lipid peroxidation and nitric oxide, suppressed antioxidants, and Nrf2/HO-1 signaling in the liver and kidney of rats. MSNs up-regulated the expression of liver and kidney TLR4, MyD88, NF-κB p65, and caspase-3 and increased serum pro-inflammatory cytokines. In addition, MSNs activated the JAK2/STAT3 signaling pathway, down-regulated peroxisome proliferator activated receptor gamma (PPARγ), and promoted fibrosis evidenced by the increased collagen expression and deposition. In conclusion, this study conferred novel information on the role of ROS and deregulated TLR4/MyD88/NF-κB, JAK2/STAT3, PPARγ, and Nrf2/ARE/HO-1 signaling pathways in MSNs hepatic and nephrotoxicity. These findings provide experimental evidence for further studies employing genetic and pharmacological strategies to evaluate the safety of MSNs for their use in nanomedicine.

Eudragit L-100 Capsules Aromatize and Quaternerize Chitosan for Insulin Nanoparticle Oral Delivery During Toxic Oxidative Stress in Rat Liver and Kidney

2020 ◽  
Vol 8 (3) ◽  
pp. 239-254 ◽  
Author(s):  
Reza Mahjub ◽  
Farzane K. Najafabadi ◽  
Narges Dehkhodaei ◽  
Nejat Kheiripour ◽  
Amir N. Ahmadabadi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oral Administration ◽  
Oral Delivery ◽  
Biochemical Parameters ◽  
Kidney Injury ◽  
Regular Insulin ◽  
Treated Group ◽  
Histopathological Change ◽  
Diabetic Rats ◽  
Liver And Kidney

Background: Insulin, like most peptides, is classified as a hydrophilic and macromolecular drug that is considered as a low permeable and unstable compound in the gastrointestinal (GI) tract. The acidic condition of the stomach can degrade insulin molecules. Moreover, the presence of proteolytic activities of some enzymes such as trypsin and chymotrypsin can hydrolyze amide-bonds between various amino-acids in the structures of peptides and proteins. However, due to its simplicity and high patient compliance, oral administration is the most preferred route of systemic drug delivery, and for the development of an oral delivery system, some obstacles in oral administration of peptides and proteins including low permeability and low stability of the proteins in GI should be overcome. Objective: In this study, the effects of orally insulin nanoparticles (INPs) prepared from quaternerized N-aryl derivatives of chitosan on the biochemical factors of the liver in diabetic rats were studied. Methods: INPs composed of methylated (amino benzyl) chitosan were prepared by the PEC method. Lyophilized INPs were filled in pre-clinical capsules, and the capsules were enteric-coated with Eudragit L100. Twenty Male Wistar rats were randomly divided into four groups: group1: normal control rats, group 2: diabetic rats, group 3: diabetic rats received capsules INPs(30 U/kg/day, orally), group 4: the diabetic rats received regular insulin (5 U/kg/day, subcutaneously). At the end of the treatment, serum, liver and kidney tissues were collected. Biochemical parameters in serum were measured using spectrophotometric methods. Also, oxidative stress was measured in plasma, liver and kidney. Histological studies were performed using H and E staining . Results: Biochemical parameters, and liver and kidney injury markers in serum of the diabetic rats that received INPs improved significantly compared with the diabetic group. INPs reduced oxidative toxic stress biomarkers in serum, liver and kidney of the diabetic treated group. Furthermore, a histopathological change was developed in the treated groups. Conclusion: Capsulated INPs can prevent diabetic liver and oxidative kidney damages (similar regular insulin). Therefore oral administration of INPs appears to be safe. Lay Summary: Although oral route is the most preferred route of administration, but oral delivery of peptides and proteins is still a challenging issue. Diabetes Mellitus may lead to severe complications, which most of them are life-threatening. In this study, we are testing the toxicity of oral insulin nanoparticles in kidney and liver of rats. For this investigation, we will prepare insulin nanoparticles composed of a quaternized derivative of chitosan. The nanoparticles will be administered orally to rats and the level of oxidative stress in their liver and kidney will be determined. The data will be compared to the subcutaneous injection of insulin.

Baicalin protects against zearalenone-induced chicks liver and kidney injury by inhibiting expression of oxidative stress, inflammatory cytokines and caspase signaling pathway

2021 ◽  
Vol 100 ◽  
pp. 108097
Author(s):  
Jingnan Xu ◽  
Shurou Li ◽  
Liqiang Jiang ◽  
Xinxin Gao ◽  
Wei Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Kidney Injury ◽  
Liver And Kidney

scholarly journals N-Acetylcysteine Alleviated the Deltamethrin-Induced Oxidative Cascade and Apoptosis in Liver and Kidney Tissues

2022 ◽  
Vol 19 (2) ◽  
pp. 638
Author(s):  
Ali Allam ◽  
Ahmed Abdeen ◽  
Hari Prasad Devkota ◽  
Samar S. Ibrahim ◽  
Gehan Youssef ◽  
...  
Keyword(s):  
Broiler Chickens ◽  
Caspase 3 ◽  
Kidney Injury ◽  
Renal Tissue ◽  
Health Issues ◽  
Significant Protection ◽  
Gene Expressions ◽  
Molecular Alterations ◽  
Liver And Kidney ◽  
Antioxidant Markers

Deltamethrin (DLM) is a synthetic pyrethroid with anti-acaricide and insecticidal properties. It is commonly used in agriculture and veterinary medicine. Humans and animals are exposed to DLM through the ingestion of polluted food and water, resulting in severe health issues. N-acetylcysteine (NAC) is a prodrug of L-cysteine, the precursor to glutathione. It can restore the oxidant-antioxidant balance. Therefore, this research aimed to examine whether NAC may protect broiler chickens against oxidative stress, at the level of biochemical and molecular alterations caused by DLM intoxication. The indicators of liver and kidney injury in the serum of DLM-intoxicated and NAC-treated groups were examined. Furthermore, lipid peroxidation, antioxidant markers, superoxide dismutase activity, and apoptotic gene expressions (caspase-3 and Bcl-2) were investigated. All parameters were significantly altered in the DLM-intoxicated group, suggesting that DLM could induce oxidative damage and apoptosis in hepato-renal tissue. The majority of the changes in the studied parameters were reversed when NAC therapy was used. In conclusion, by virtue of its antioxidant and antiapoptotic properties, NAC enabled the provision of significant protection effects against DLM-induced hepato-renal injury.

scholarly journals Identification of hub genes and networks in cisplatin-induced acute kidney injury

2021 ◽  
Author(s):  
Lingyun Yang ◽  
Jinwen Xu ◽  
Xunwei Liu ◽  
Yun Cheng ◽  
Hongxia Zhou ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Health Hazard ◽  
Herbal Medicines ◽  
Kidney Injury ◽  
Hub Genes ◽  
Chinese Herbal Medicines ◽  
Chinese Herbal ◽  
Ppi Networks

Abstract Acute kidney injury induced by cisplatin poses a serious health hazard to patients. Thus, this study was undertaken to elucidate key signaling pathways and hub genes relevant for therapeutic intervention involved in cisplatin-induced acute kidney injury(CI-AKI) by bioinformatics. We identified differentially expressed genes(DEGs) by R language on GSE106993 and GSE153625 datasets, downloaded from Gene Expression Omnibus (GEO). GO enrichment analysis and KEGG analysis were used to identify the main functions of common differential genes. The STRING database was used to construct protein-protein interaction (PPI) networks and hub genes were selected by Cytoscape. TransmiR v2.0 database and miRWalk2.0 database were used to construct transcription factor (TF)/microRNA (miRNA)/mRNA networks. Chinese herbal medicines targeting hub genes were screened by the ETMC database. 817 up-regulated genes and 769 down-regulated genes were obtained in CI-AKI model. Tumor necrosis factor(TNF) signaling pathway, P53 signaling, and metabolic signaling pathway are important pathways in CI-AKI. 8 hub genes were identified through PPI (Trp53、Egf、Stat3、Jun、Casp3、Cdh1、Ptgs2、Cat). We also constructed TF/microRNA/mRNA regulatory networks, including 2 TFs, 4 miRNAs and 214 mRNAs. The results of ETMC database analysis showed that Sang-Ye and Ban-Xia could be used for the treatment of CI-AKI. In this study, we identified 8 hub genes and 3 important signaling pathways in CI-AKI model by bioinformatics analysis, which provide targets for the treatment of CI-AKI. And the two Chinese herbal medicines obtained from our research, Sang-Ye and Ban-Xia, are expected to be used for the treatment of CI-AKI. Meanwhile, the TF/miRNA/mRNA networks we constructed are helpful to the further study of the mechanism of CI-AKI.

scholarly journals Tacrolimus Toxicity due to Biliary Obstruction in a Combined Kidney and Liver Transplant Recipient

2017 ◽  
Vol 2017 ◽  
pp. 1-4 ◽  
Author(s):  
Samuel Chan ◽  
Michael T. Burke ◽  
David W. Johnson ◽  
Ross S. Francis ◽  
David W. Mudge
Keyword(s):  
Transplant Recipient ◽  
Biliary Obstruction ◽  
Kidney Transplant Recipient ◽  
Kidney Injury ◽  
Therapeutic Window ◽  
Therapeutic Drug ◽  
Blood Levels ◽  
Liver And Kidney ◽  
The Impact ◽  
Very High

The immunosuppressant tacrolimus has a narrow therapeutic window, necessitating therapeutic drug monitoring to maintain efficacy and minimise toxicity. There are very few reports examining the impact of impaired biliary excretion on tacrolimus blood levels or toxicity. We report the case of a 26-year-old combined liver and kidney transplant recipient, who developed acute biliary obstruction leading to tacrolimus toxicity with very high blood tacrolimus levels. Despite a careful evaluation, no alternative cause was found for her acute kidney injury, and her kidney function returned to previous baseline within several days following treatment of the biliary obstruction and temporary withdrawal of tacrolimus.

Annonacin Suppresses Tumor Promoting Stage in Two Stage Mouse Skin Tumorigenesis via Modulation of Multiple Cancer Signaling Pathways

2018 ◽  
Author(s):  
Mohd Rohaizad Md Roduan ◽  
Norhafizah Mohtarrudin ◽  
Roslida Abd Hamid
Keyword(s):  
Signaling Pathways ◽  
Histopathological Examination ◽  
Mouse Skin ◽  
Latency Period ◽  
Multiple Cancer ◽  
Two Stage ◽  
Skin Tumorigenesis ◽  
Cancer Signaling ◽  
Liver And Kidney

Annonacin, an annonaceous acetogenin isolated from Annona muricata has been reported to be strongly cytotoxic against various cell lines, in vitro. Nevertheless, its effect against in vivo tumor promoting activity has not been reported yet. Therefore, this study was aimed to investigate antitumor-promoting activity of annonacin via in vivo two-stage mouse skin tumorigenesis model and its molecular pathways involved. Annonacin 85 nM was topically applied to DMBA/TPA-induced ICR mice for 22 weeks of treatment. Histopathological examination of skin, liver and kidney as well as genes and proteins expression analysis were conducted. Annonacin significantly increased the tumor latency period and also reduced the tumor incidence, tumor burden and tumor volume, respectively. In addition, it also suppressed tumorigenesis manifested by significant reduction of hyperkeratosis, dermal papillae and number of keratin pearls on skin tissues. Annonacin also appeared to be non-toxic to liver and kidney. Significant modulation of both AKT, ERK, MTOR, p38, PTEN and Src genes and proteins were also observed in annonacin-targeted signaling pathway(s) against tumorigenesis. Collectively, results of this study indicate that annonacin is a potential therapeutic compound targeting tumor promoting stage in skin tumorigenesis by modulating multiple gene and protein in cancer signaling pathways without apparent toxicity.

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