Protective Effects of Low Dose Vorinostat on Cisplatin-induced Nephrotoxicity in Rats

2020 ◽  
Vol 13 ◽  
Author(s):  
Omnyah M. O. Bashraf ◽  
Ahmed S. Ali ◽  
Hala S. A. Eweis ◽  
Soad S. Ali
Keyword(s):  
Single Dose ◽  
Therapeutic Potential ◽  
Control Group ◽  
Histopathological Analysis ◽  
Protective Effects ◽  
Necrosis Factor Alpha ◽  
In Vivo Models ◽  
Pre Treatment

Background and Aim: Cisplatin (cis-diamminedichloroplatinum [II]; CDDP) is the most widely used drug in cancer chemotherapy. The nephrotoxicity of CDDP is one of its major side effects. Vorinostat (VST) has been reported to have antioxidant and anti-inflammatory effects in both in-vitro and in vivo models. The present study aimed to explore the potential protective effects of VST against CDDP-induced nephrotoxicity in rats. Materials and Methods: The rats were randomly divided into 4 groups; control group, CDDP group (received CDDP 7.5 mg/kg IP single dose 5 days before the end of the experiment), VST group, (received VST 15 mg/kg/day by gastric gavage for 28 days), and CDDP + VST group (received CDDP + VST as above). Blood and kidney samples were collected on the 28th day for biochemical and histopathological examinations. Results : Administration of CDDP single dose (7.5 mg/kg IP) 5 days before the end of the experiment (at day 23) produced a significant decrease in renal glutathione levels and a significant increase in serum urea nitrogen, creatinine, renal malondialdehyde, tumor necrosis factor-alpha, tumor suppressor protein (p53) and nuclear factor kappa B levels compared to the control group. Pre-treatment with VST for 28 days significantly attenuated all unfavorable changes of these parameters. Histopathological analysis showed that VST significantly decreased kidney inflammatory and degenerative changes induced by CDDP. VST also significantly increased Bcl-2 and decreased Caspas-3 immunoexpression in renal tissues. Conclusion: These results suggest that VST alleviates CDDP-induced nephrotoxicity in rats showing a novel therapeutic potential for the management of nephrotoxicity induced by CDDP.

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 Protective effects of orally applied fullerenol nano particles in rats after a single dose of doxorubicin

2011 ◽  
Vol 65 (3) ◽  
pp. 329-337 ◽  
Author(s):  
Ivana Icevic ◽  
Aleksandar Vukmirovic ◽  
Branislava Srdjenovic ◽  
Jan Sudji ◽  
Aleksandar Djordjevic ◽  
...  
Keyword(s):  
Biological Activity ◽  
Single Dose ◽  
Antioxidant Properties ◽  
Water Soluble ◽  
Nano Particles ◽  
Protective Effects ◽  
In Vivo Models ◽  
Nephroprotective Effect

Polyhydroxylated, water soluble, fullerenol C60(OH)24 nano particles (FNP) in vitro and in vivo models, showed an expressive biological activity. The goal of this work was to investigate the potential protective effects of orally applied FNP on rats after a single dose of doxorubicin (DOX) (8 mg/kg (i.p.)) 6 h after the last application of FNP. After the last drug administration, the rats were sacrificed, and the blood and tissues were taken for the analysis. Biochemical and pathological results obtained in this study indicate that fullerenol (FNP), in H2O:DMSO (80:20, w/w) solution given orally in final doses of 10, 14.4, and 21.2 mg/kg three days successively, has the protective (hepatoprotective and nephroprotective) effect against doxorubicin-induced cytotoxicity via its antioxidant properties.

scholarly journals GSK-3β in Pancreatic Cancer: Spotlight on 9-ING-41, Its Therapeutic Potential and Immune Modulatory Properties

Biology ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 610
Author(s):  
Robin Park ◽  
Andrew L. Coveler ◽  
Ludimila Cavalcante ◽  
Anwaar Saeed
Keyword(s):  
Pancreatic Cancer ◽  
Therapeutic Potential ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
In Vivo Models ◽  
Gsk 3Β ◽  
Early Phase Clinical Trials

Glycogen synthase kinase-3 beta is a ubiquitously and constitutively expressed molecule with pleiotropic function. It acts as a protooncogene in the development of several solid tumors including pancreatic cancer through its involvement in various cellular processes including cell proliferation, survival, invasion and metastasis, as well as autophagy. Furthermore, the level of aberrant glycogen synthase kinase-3 beta expression in the nucleus is inversely correlated with tumor differentiation and survival in both in vitro and in vivo models of pancreatic cancer. Small molecule inhibitors of glycogen synthase kinase-3 beta have demonstrated therapeutic potential in pre-clinical models and are currently being evaluated in early phase clinical trials involving pancreatic cancer patients with interim results showing favorable results. Moreover, recent studies support a rationale for the combination of glycogen synthase kinase-3 beta inhibitors with chemotherapy and immunotherapy, warranting the evaluation of novel combination regimens in the future.

scholarly journals Plant-Derived Nano and Microvesicles for Human Health and Therapeutic Potential in Nanomedicine

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 498
Author(s):  
Mariaevelina Alfieri ◽  
Antonietta Leone ◽  
Alfredo Ambrosone
Keyword(s):  
Therapeutic Potential ◽  
Biological Activities ◽  
Plant Biotechnology ◽  
Bioactive Metabolites ◽  
Anticancer Activities ◽  
Long Distance ◽  
In Vivo Models ◽  
Therapeutic Tools

Plants produce different types of nano and micro-sized vesicles. Observed for the first time in the 60s, plant nano and microvesicles (PDVs) and their biological role have been inexplicably under investigated for a long time. Proteomic and metabolomic approaches revealed that PDVs carry numerous proteins with antifungal and antimicrobial activity, as well as bioactive metabolites with high pharmaceutical interest. PDVs have also been shown to be also involved in the intercellular transfer of small non-coding RNAs such as microRNAs, suggesting fascinating mechanisms of long-distance gene regulation and horizontal transfer of regulatory RNAs and inter-kingdom communications. High loading capacity, intrinsic biological activities, biocompatibility, and easy permeabilization in cell compartments make plant-derived vesicles excellent natural or bioengineered nanotools for biomedical applications. Growing evidence indicates that PDVs may exert anti-inflammatory, anti-oxidant, and anticancer activities in different in vitro and in vivo models. In addition, clinical trials are currently in progress to test the effectiveness of plant EVs in reducing insulin resistance and in preventing side effects of chemotherapy treatments. In this review, we concisely introduce PDVs, discuss shortly their most important biological and physiological roles in plants and provide clues on the use and the bioengineering of plant nano and microvesicles to develop innovative therapeutic tools in nanomedicine, able to encompass the current drawbacks in the delivery systems in nutraceutical and pharmaceutical technology. Finally, we predict that the advent of intense research efforts on PDVs may disclose new frontiers in plant biotechnology applied to nanomedicine.

scholarly journals Probiotic and Functional Properties of Limosilactobacillus reuteri INIA P572

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1860
Author(s):  
Patricia Diez-Echave ◽  
Izaskun Martín-Cabrejas ◽  
José Garrido-Mesa ◽  
Susana Langa ◽  
Teresa Vezza ◽  
...  
Keyword(s):  
In Vitro Assays ◽  
Immunomodulatory Activity ◽  
Probiotic Properties ◽  
Protective Effects ◽  
Mice Model ◽  
In Vivo Models ◽  
Food Borne ◽  
Gastrointestinal Conditions

Limosilactobacillus reuteri INIA P572 is a strain able to produce the antimicrobial compound reuterin in dairy products, exhibiting a protective effect against some food-borne pathogens. In this study, we investigated some probiotic properties of this strain such as resistance to gastrointestinal passage or to colonic conditions, reuterin production in a colonic environment, and immunomodulatory activity, using different in vitro and in vivo models. The results showed a high resistance of this strain to gastrointestinal conditions, as well as capacity to grow and produce reuterin in a human colonic model. Although the in vitro assays using the RAW 264.7 macrophage cell line did not demonstrate direct immunomodulatory properties, the in vivo assays using a Dextran Sulphate Sodium (DSS)-induced colitic mice model showed clear immunomodulatory and protective effects of this strain.

scholarly journals Protective effects of carbonic anhydrase inhibition in brain ischaemia in vitro and in vivo models

2021 ◽  
Vol 36 (1) ◽  
pp. 964-976
Author(s):  
Ilaria Dettori ◽  
Irene Fusco ◽  
Irene Bulli ◽  
Lisa Gaviano ◽  
Elisabetta Coppi ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Protective Effects ◽  
Brain Ischaemia ◽  
In Vivo Models ◽  
Carbonic Anhydrase Inhibition

scholarly journals Sulfasalazine modifies metabolic profiles and enhances cisplatin chemosensitivity on cholangiocarcinoma cells in in vitro and in vivo models

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Malinee Thanee ◽  
Sureerat Padthaisong ◽  
Manida Suksawat ◽  
Hasaya Dokduang ◽  
Jutarop Phetcharaburanin ◽  
...  
Keyword(s):  
Redox Regulation ◽  
Treated Group ◽  
Control Group ◽  
High Recurrence Rate ◽  
Nucleic Acid Metabolism ◽  
In Vivo Models ◽  
Tryptophan Degradation ◽  
Xenograft Mice

Abstract Background Sulfasalazine (SSZ) is widely known as an xCT inhibitor suppressing CD44v9-expressed cancer stem-like cells (CSCs) being related to redox regulation. Cholangiocarcinoma (CCA) has a high recurrence rate and no effective chemotherapy. A recent report revealed high levels of CD44v9-positive cells in CCA patients. Therefore, a combination of drugs could prove a suitable strategy for CCA treatment via individual metabolic profiling. Methods We examined the effect of xCT-targeted CD44v9-CSCs using sulfasalazine combined with cisplatin (CIS) or gemcitabine in CCA in vitro and in vivo models and did NMR-based metabolomics analysis of xenograft mice tumor tissues. Results Our findings suggest that combined SSZ and CIS leads to a higher inhibition of cell proliferation and induction of cell death than CIS alone in both in vitro and in vivo models. Xenograft mice showed that the CD44v9-CSC marker and CK-19-CCA proliferative marker were reduced in the combination treatment. Interestingly, different metabolic signatures and significant metabolites were observed in the drug-treated group compared with the control group that revealed the cancer suppression mechanisms. Conclusions SSZ could improve CCA therapy by sensitization to CIS through killing CD44v9-positive cells and modifying the metabolic pathways, in particular tryptophan degradation (i.e., kynurenine pathway, serotonin pathway) and nucleic acid metabolism.

scholarly journals Sphingosine 1-phosphate in inflammation

2020 ◽  
Vol 4 (6) ◽  
Author(s):  
Lijuan Li ◽  
Lixia An ◽  
Lifang Li ◽  
Yongjuan Zhao
Keyword(s):  
Plasma Membrane ◽  
Drug Targets ◽  
Therapeutic Potential ◽  
Cell Types ◽  
In Vivo Models ◽  
Integral Role ◽  
Sphingosine 1 Phosphate ◽  
And Migration

Sphingolipids are formed via the metabolism of sphingomyelin, aconstituent of the plasma membrane, or by denovosynthesis. Enzymatic pathways result in the formation of several different lipid mediators, which are known to have important roles in many cellular processes, including proliferation, apoptosis and migration. Several studies now suggest that these sphingolipid mediators, including ceramide, ceramide 1-phosphate and sphingosine 1-phosphate (S1P), are likely to have an integral role in in?ammation. This can involve, for example, activation of pro-in?ammatory transcription factors in different cell types and induction of cyclooxygenase-2, leading to production of pro-in?ammatory prostaglandins. The mode of action of each sphingolipid is different. Increased ceramide production leads to the formation of ceramide-rich areas of the membrane, which may assemble signalling complexes, whereas S1P acts via high-af?nity G-protein-coupled S1P receptors on the plasma membrane. Recent studies have demonstrated that in vitro effects of sphingolipids on in?ammation can translate into in vivo models. This review will highlight the areas of research where sphingolipids are involved in in?ammation and the mechanisms of action of each mediator. In addition, the therapeutic potential of drugs that alter sphingolipid actions will be examined with reference to disease states, such as asthma and in?ammatory bowel disease, which involve important in?ammatory components. A signi?cant body of research now indicates that sphingolipids are intimately involved in the in?ammatory process and recent studies have demonstrated that these lipids, together with associated enzymes and receptors, can provide effective drug targets for the treatment of pathological in?ammation.

scholarly journals Anti-Inflammatory Potential of Daturaolone from Datura innoxia Mill.: In Silico, In Vitro and In Vivo Studies

2021 ◽  
Vol 14 (12) ◽  
pp. 1248
Author(s):  
Muhammad Waleed Baig ◽  
Humaira Fatima ◽  
Nosheen Akhtar ◽  
Hidayat Hussain ◽  
Mohammad K. Okla ◽  
...  
Keyword(s):  
In Silico ◽  
Therapeutic Potential ◽  
In Vivo Studies ◽  
Metabolic Reaction ◽  
Datura Innoxia ◽  
In Vivo Models ◽  
Immobility Time ◽  
Anti Inflammatory

Exploration of leads with therapeutic potential in inflammatory disorders is worth pursuing. In line with this, the isolated natural compound daturaolone from Datura innoxia Mill. was evaluated for its anti-inflammatory potential using in silico, in vitro and in vivo models. Daturaolone follows Lipinski’s drug-likeliness rule with a score of 0.33. Absorption, distribution, metabolism, excretion and toxicity prediction show strong plasma protein binding; gastrointestinal absorption (Caco-2 cells permeability = 34.6 nm/s); no blood–brain barrier penetration; CYP1A2, CYP2C19 and CYP3A4 metabolism; a major metabolic reaction, being aliphatic hydroxylation; no hERG inhibition; and non-carcinogenicity. Predicted molecular targets were mainly inflammatory mediators. Molecular docking depicted H-bonding interaction with nuclear factor kappa beta subunit (NF-κB), cyclooxygenase-2, 5-lipoxygenase, phospholipase A2, serotonin transporter, dopamine receptor D1 and 5-hydroxy tryptamine. Its cytotoxicity (IC50) value in normal lymphocytes was >20 µg/mL as compared to cancer cells (Huh7.5; 17.32 ± 1.43 µg/mL). Daturaolone significantly inhibited NF-κB and nitric oxide production with IC50 values of 1.2 ± 0.8 and 4.51 ± 0.92 µg/mL, respectively. It significantly reduced inflammatory paw edema (81.73 ± 3.16%), heat-induced pain (89.47 ± 9.01% antinociception) and stress-induced depression (68 ± 9.22 s immobility time in tail suspension test). This work suggests a possible anti-inflammatory role of daturaolone; however, detailed mechanistic studies are still necessary to corroborate and extrapolate the findings.

scholarly journals Mechanism of KLF4 Protection against Acute Liver Injury via Inhibition of Apelin Signaling

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Weitao Ji ◽  
Hongyun Shi ◽  
Hailin Shen ◽  
Jing Kong ◽  
Jiayi Song ◽  
...  
Keyword(s):  
Liver Injury ◽  
Signaling Pathway ◽  
Acute Liver Injury ◽  
Control Group ◽  
Necrosis Factor Alpha ◽  
Protein Levels ◽  
Klf4 Expression ◽  
Mrna And Protein Expression

Krüppel-like factor 4 (KLF4) is a key transcription factor that regulates genes involved in the proliferation or differentiation in different tissues. Apelin plays roles in cardiovascular functions, metabolic disease, and homeostatic disorder. However, the biological function of apelin in liver disease is still ongoing. In this study, we investigated the mechanism of KLF4-mediated protection against acute liver injury via the inhibition of the apelin signaling pathway. Mice were intraperitoneally injected with carbon tetrachloride (CCl4; 0.2 mL dissolved in 100 mL olive oil, 10 mL/kg) to establish an acute liver injury model. A KLF4 expression plasmid was injected through the tail vein 48 h before CCl4 treatment. In cultured LX-2 cells, pAd-KLF4 or siRNA KLF4 was overexpressed or knockdown, and the mRNA and protein levels of apelin were determined. The results showed that the apelin serum level in the CCl4-injected group was higher than that of control group, and the expression of apelin in the liver tissues was elevated while KLF4 expression was decreased in the CCl4-injected group compared to the KLF4-plasmid-injected group. HE staining revealed serious hepatocellular steatosis in the CCl4-injected mice, and KLF4 alleviated this steatosis in the mice injected with KLF4 plasmid. In vitro experiments showed that tumor necrosis factor-alpha (TNF-α) could downregulate the transcription and translation levels of apelin in LX-2 cells and also upregulate KLF4 mRNA and protein expression. RT-PCR and Western blotting showed that the overexpression of KLF4 markedly decreased basal apelin expression, but knockdown of KLF4 restored apelin expression in TNF-α-treated LX-2 cells. These in vivo and in vitro experiments suggest that KLF4 plays a key role in inhibiting hepatocellular steatosis in acute liver injury, and that its mechanism might be the inhibition of the apelin signaling pathway.

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