Effects of quercetin loaded nanostructured lipid carriers on the paraquat-induced toxicity in human lymphocytes

Ahmadian, Elham; Eftekhari, Aziz; Kavetskyy, Taras; Khosroushahi, Ahmad Yari; Türksoy, Vugar Ali; Khalilov, Rovshan

doi:10.1016/j.pestbp.2020.104586

Cited by 94 publications

(29 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…38 Apoptotic machinery activation is linked to mitochondria, where p53 activation promotes the transcription of pro-apoptotic genes such as Bax, resulting in enhanced mitochondrial permeabilization and release of cytochrome c, which stimulates caspase-3 and initiates apoptosis via an oxidative stress related mitochondrial pathway. 39 It was confirmed that cisplatin-mediated renal injury was associated with cell apoptosis. 9 we revealed that cisplatin induced activation of the executioner caspase-3 and p53, the upstream regulator of the apoptotic pathway, thus triggering cell apoptosis.…”

Section: Discussionmentioning

confidence: 90%

A nano based approach to alleviate cisplatin induced nephrotoxicity

Anees

Abdel-Hamid

Elkady

2021

Int J Immunopathol Pharmacol

View full text Add to dashboard Cite

Background and objective Cisplatin, an effective drug against cancer, commonly induces nephrotoxicity; limiting its therapeutic efficacy and application. In this study, Cisplatin NanoComposite (Cis NC) was formulated successfully from irradiated chitosan coated Cisplatin and MgO nanoparticles (CHIT/Cis/MgO NPs) to promote cisplatin release in a more sustained manner to improve therapeutic efficacy via the reduction of its nephrotoxicity. To compare the relative induced renal toxicity of cisplatin with Cisplatin NanoComposite, histological and biochemical mechanisms underlying nephrotoxicity were investigated. Methods Thirty rats were equally separated to three groups, first group received saline injections and adjusted as the control group, the second group was injected intra-peritoneal with cisplatin 0.64 mg/kg b. wt./day for 6 weeks, the third group was injected intra-peritoneal with Cis NC 5.75 mg/kg b. wt. daily for 6 weeks. Results Cisplatin-induced renal functional impairment and histopathological damages in the kidney; also, cisplatin disrupted the balance of the redox system in renal tissue, stimulated the inflammatory reactions in the kidney via triggering signal transducer and activator of transcription-1 (STAT1) dependent pathways. Moreover, Cisplatin-induced activation of mammalian target of rapamycin mTOR and inactivation of AMPK/PI3K/Akt signal pathway, and was coupled with induction of p53 activity and the executioner caspase3 to induce apoptotic renal cell death. On the other hand, Cis NC exerted a minimal stimulatory effect on apoptotic and inflammatory signal cascade with negligible renal functional and morphological alterations. Conclusion We postulated that Cis NC may be a valued possible drug to decrease the cytotoxicity of cisplatin thus reserves the renal function and structure.

show abstract

Section: Discussionmentioning

confidence: 90%

A nano based approach to alleviate cisplatin induced nephrotoxicity

Anees

Abdel-Hamid

Elkady

2021

Int J Immunopathol Pharmacol

View full text Add to dashboard Cite

show abstract

“…A similar strategy was adopted to find the effective synergic combination of fludilone, a microtubule targeting anticancer agent, and panaxytriol, a cytoprotective agent against MX-1 cells . Thus, the approach of loading the active molecules with different modes of cytotoxic action into a targeted n-DS can help in overcoming the off-target toxicity, drug resistance, and other issues generated due to the higher dosage of the application of a single drug. Two pharmacological molecules with different functional properties when integrated into a single nanoplatform is expected to produce enhanced anticancer effects …”

Section: Resultsmentioning

confidence: 99%

Targeted Delivery Polymeric Nanosystem Reinforced by Synergism of Embilin and RPI-1 for Therapeutics of Pancreatic Cancer

Arya

Joseph

Murali

et al. 2022

ACS Appl. Nano Mater.

View full text Add to dashboard Cite

Pancreatic cancer (PC) is an aggressive form of malignancy with poor prognosis and feeble survival benefits. Here, we have ventured a personalized nanoconstruct constituted of the synergistic therapeutic benefit of two agents, namely, embelin and RPI-1, coloaded in a biodegradable nanodelivery system which has been tethered with a targeting peptide substrate for plectin-1, a surface biomarker of PC. The phytomolecule embelin, an alkylsubstituted hydroxyl benzoquinone isolated from the seeds of Embelia ribes, is introduced in this combination therapy and is known as a natural inhibitor of X-linked inhibitor of apoptosis protein and executes anticancer activity via the NF-kB pathway. On the other hand, tyrosine-protein kinase Met (c-MET) is a biomarker of PC wherein the molecule RPI-1, an indolinone derivative, is selective to the c-MET inhibitor. After conducting a series of systematic cytotoxicity evaluations followed by enumeration of combination index, a standalone synergic ratio of embelin and RPI-1 (1: 4.7) was evolved that executed a benchmarked PC-selective toxicity profile. This composition was precisely incorporated within a PC-targeted PLGA−chitosan core− shell nanoparticle delivery system for avoiding collateral damages. Appealing features of the nanoconstruct including biocompatibility, PC-targeted uptake, and subsequent execution of cytotoxicity and antimetastatic properties have been systematically evaluated on the PC cell line PANC-1 and later on the xenograft PC model of zebra fish. Finally, the unique metabolic changes associated with the therapeutic action of embelin and RPI-1 was scrutinized by surface-enhanced Raman spectroscopy and liquid chromatography−mass spectrometry analysis wherein almost 25 metabolites associated with the cell death pathway deciphered a significant variation. Therefore, this proof-of-concept personalized nanodelivery warrants further preclinical and clinical evaluations for the management of PC.

show abstract

“…The generic model, applying descriptors of coated NPs (size, surface energy components and surface potential) and cells (surface energy components and surface potential), predict exocytosis rate constants of various NPs by calculating interactions between NPs and membranes. The model may find use in biomedicine via cellular or mitochondrial targeting 62 by NPs or evaluating their antioxidant and anti-genotoxic capacity 63 . Our model suggests that transport experiments of NPs in the future can provide accurate surface chemical information to provide sufficient data for prediction of NPs accumulation in cells or organs, e.g., PBPK modeling 17 .…”

Section: Discussionmentioning

confidence: 99%

Generic prediction of exocytosis rate constants by size-based surface energies of nanoparticles and cells

Wang

Scheepers

et al. 2022

Sci Rep

View full text Add to dashboard Cite

Nanotechnology brings benefits in fields such as biomedicine but nanoparticles (NPs) may also have adverse health effects. The effects of surface-modified NPs at the cellular level have major implications for both medicine and toxicology. Semi-empirical and mechanism-based models aid to understand the cellular transport of various NPs and its implications for quantitatively biological exposure while avoiding large-scale experiments. We hypothesized relationships between NPs-cellular elimination, surface functionality and elimination pathways by cells. Surface free energy components were used to characterize the transport of NPs onto membranes and with lipid vesicles, covering both influences by size and hydrophobicity of NPs. The model was built based on properties of neutral NPs and cells, defining Van de Waals forces, electrostatic forces and Lewis acid–base (polar) interactions between NPs and vesicles as well as between vesicles and cell membranes. We yielded a generic model for estimating exocytosis rate constants of various neutral NPs by cells based on the vesicle-transported exocytosis pathways. Our results indicate that most models are well fitted (R2 ranging from 0.61 to 0.98) and may provide good predictions of exocytosis rate constants for NPs with differing surface functionalities (prediction errors are within 2 times for macrophages). Exocytosis rates differ between cancerous cells with metastatic potential and non-cancerous cells. Our model provides a reference for cellular elimination of NPs, and intends for medical applications and risk assessment.

show abstract

Effects of quercetin loaded nanostructured lipid carriers on the paraquat-induced toxicity in human lymphocytes

Cited by 94 publications

References 46 publications

A nano based approach to alleviate cisplatin induced nephrotoxicity

A nano based approach to alleviate cisplatin induced nephrotoxicity

Targeted Delivery Polymeric Nanosystem Reinforced by Synergism of Embilin and RPI-1 for Therapeutics of Pancreatic Cancer

Generic prediction of exocytosis rate constants by size-based surface energies of nanoparticles and cells

Contact Info

Product

Resources

About