Engineered biomimetic nanoabsorbent for cellular detoxification of chemotherapeutics

RSC Advances ◽  
2016 ◽  
Vol 6 (39) ◽  
pp. 33003-33008 ◽  
Author(s):  
Tuyen Duong Thanh Nguyen ◽  
Arunkumar Pitchaimani ◽  
Mukund Bahadur Koirala ◽  
Faqir Muhammad ◽  
Santosh Aryal
Keyword(s):  
Cellular Detoxification ◽  
Nonspecific Cytotoxicity ◽  
Detoxifying Agent

An approach to reduce the nonspecific cytotoxicity of chemotherapeutics has been put-forth using a biomimetic nanoabsorbent (NAb) as a detoxifying agent.

scholarly journals In Vitro Antioxidant Activity of Litsea martabanica Root Extract and Its Hepatoprotective Effect on Chlorpyrifos-Induced Toxicity in Rats

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1906
Author(s):  
Phraepakaporn Kunnaja ◽  
Sunee Chansakaow ◽  
Absorn Wittayapraparat ◽  
Pedcharada Yusuk ◽  
Seewaboon Sireeratawong
Keyword(s):  
Antioxidant Activity ◽  
Antioxidant Properties ◽  
Water Extract ◽  
Acetylcholinesterase Activity ◽  
Liver Cells ◽  
Scientific Data ◽  
Total Phenolic ◽  
Root Extract ◽  
Antioxidant Power ◽  
Detoxifying Agent

In Thailand, people in the highland communities whose occupational exposure to pesticides used the root of Litsea martabanica as a detoxifying agent. However, the scientific data to support the traditional use of this plant are insufficient. This study aimed to evaluate the antioxidant activity and anti-pesticide potential of L. martabanica root extract. Antioxidant properties were investigated by 2,2′-diphenyl-1-picrylhydrazyl (DPPH) assay, superoxide radicals scavenging assay, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay, ferric reducing antioxidant power (FRAP), and total phenolic content determination. In all assays, L. martabanica extracts and their fractions exhibited high antioxidant activities differently. The water extract is traditionally used as a detoxifying agent. Therefore, it was chosen for in vivo experiments. The rats received the extract in a way that mimics the traditional methods of tribal communities followed by chlorpyrifos for 16 days. The results showed that acetylcholinesterase activity decreases in pesticide-exposed rats. Treatment with the extract caused increasing acetylcholinesterase activity in the rats. Therefore, L. martabanica extract may potentially be used as a detoxifying agent, especially for the chlorpyrifos pesticide. The antioxidant properties of L. martabanica may provide a beneficial effect by protecting liver cells from damage caused by free radicals. Histopathology results revealed no liver cell necrosis and showed the regeneration of liver cells in the treatment group. L. martabanica extract did not cause changes in behavior, liver weight, hematological and biochemical profiles of the rats.

Arsenic, Mechanisms of Cellular Detoxification

2013 ◽  
pp. 159-162
Author(s):  
Ebany J. Martinez-Finley ◽  
Michael Aschner
Keyword(s):  
Cellular Detoxification

scholarly journals Catalytic and structural contributions for glutathione-binding residues in a Delta class glutathione S-transferase

2004 ◽  
Vol 382 (2) ◽  
pp. 751-757 ◽  
Author(s):  
Pakorn WINAYANUWATTIKUN ◽  
Albert J. KETTERMAN
Keyword(s):  
Binding Site ◽  
Active Site ◽  
Structural Integrity ◽  
Catalytic Mechanism ◽  
Tertiary Structure ◽  
Site Directed Mutagenesis ◽  
Active Site Residues ◽  
Anopheles Dirus ◽  
Steady State Kinetics ◽  
Cellular Detoxification

Glutathione S-transferases (GSTs) are dimeric proteins that play a major role in cellular detoxification. The GSTs in mosquito Anopheles dirus species B, an important malaria vector in South East Asia, are of interest because they can play an important role in insecticide resistance. In the present study, we characterized the Anopheles dirus (Ad)GST D3-3 which is an alternatively spliced product of the adgst1AS1 gene. The data from the crystal structure of GST D3-3 shows that Ile-52, Glu-64, Ser-65, Arg-66 and Met-101 interact directly with glutathione. To study the active-site function of these residues, alanine substitution site-directed mutagenesis was performed resulting in five mutants: I52A (Ile-52→Ala), E64A, S65A, R66A and M101A. Interestingly, the E64A mutant was expressed in Escherichia coli in inclusion bodies, suggesting that this residue is involved with the tertiary structure or folding property of this enzyme. However, the I52A, S65A, R66A and M101A mutants were purified by glutathione affinity chromatography and the enzyme activity characterized. On the basis of steady-state kinetics, difference spectroscopy, unfolding and refolding studies, it was concluded that these residues: (1) contribute to the affinity of the GSH-binding site (‘G-site’) for GSH, (2) influence GSH thiol ionization, (3) participate in kcat regulation by affecting the rate-limiting step of the reaction, and in the case of Ile-52 and Arg-66, influenced structural integrity and/or folding of the enzyme. The structural perturbations from these mutants are probably transmitted to the hydrophobic-substrate-binding site (‘H-site’) through changes in active site topology or through effects on GSH orientation. Therefore these active site residues appear to contribute to various steps in the catalytic mechanism, as well as having an influence on the packing of the protein.

T lymphocyte induction of non-T cell-mediated nonspecific cytotoxicity. Introduction mechanisms

1977 ◽  
Vol 7 (2) ◽  
pp. 55-61 ◽  
Author(s):  
B. F. Mackler ◽  
Peggy A. O'Neill ◽  
M. Meistrich
Keyword(s):  
T Cell ◽  
T Lymphocyte ◽  
Nonspecific Cytotoxicity

scholarly journals Chitosan-PVA and Copper Nanoparticles Improve Growth and Overexpress the SOD and JA Genes in Tomato Plants under Salt Stress

Agronomy ◽  
2018 ◽  
Vol 8 (9) ◽  
pp. 175 ◽  
Author(s):  
Hipólito Hernández-Hernández ◽  
Antonio Juárez-Maldonado ◽  
Adalberto Benavides-Mendoza ◽  
Hortensia Ortega-Ortiz ◽  
Gregorio Cadenas-Pliego ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Salt Stress ◽  
Copper Nanoparticles ◽  
Signaling Cascades ◽  
Saline Stress ◽  
Oxygen Species ◽  
Tomato Plants ◽  
Solanum Lycopersicum L ◽  
Ionic Stress ◽  
Cellular Detoxification

Saline stress severely affects the growth and productivity of plants. The activation of hormonal signaling cascades and reactive oxygen species (ROS) in response to salt stress are important for cellular detoxification. Jasmonic acid (JA) and the enzyme SOD (superoxide dismutase), are well recognized markers of salt stress in plants. In this study, the application of chitosan-polyvinyl alcohol hydrogels (Cs-PVA) and copper nanoparticles (Cu NPs) on the growth and expression of defense genes in tomato plants under salt stress was evaluated. Our results demonstrate that Cs-PVA and Cs-PVA + Cu NPs enhance plant growth and also promote the expression of JA and SOD genes in tomato (Solanum lycopersicum L.), under salt stress. We propose that Cs-PVA and Cs-PVA + Cu NPs mitigate saline stress through the regulation of oxidative and ionic stress.

scholarly journals Invasive fungal infections in the immunocompromised host: Mechanistic insights in an era of changing immunotherapeutics

2019 ◽  
Vol 57 (Supplement_3) ◽  
pp. S307-S317 ◽  
Author(s):  
Christopher P Eades ◽  
Darius P H Armstrong-James
Keyword(s):  
Intracellular Signaling ◽  
Fungal Pathogens ◽  
Opportunistic Infections ◽  
Fungal Infections ◽  
Immunocompromised Host ◽  
Adaptive Immune ◽  
Mechanistic Approach ◽  
Molecular Immunology ◽  
Nonspecific Cytotoxicity ◽  
Small Molecular Inhibitors

AbstractThe use of cytotoxic chemotherapy in the treatment of malignant and inflammatory disorders is beset by considerable adverse effects related to nonspecific cytotoxicity. Accordingly, a mechanistic approach to therapeutics has evolved in recent times with small molecular inhibitors of intracellular signaling pathways involved in disease pathogenesis being developed for clinical use, some with unparalleled efficacy and tolerability. Nevertheless, there are emerging concerns regarding an association with certain small molecular inhibitors and opportunistic infections, including invasive fungal diseases. This is perhaps unsurprising, given that the molecular targets of such agents play fundamental and multifaceted roles in orchestrating innate and adaptive immune responses. Nevertheless, some small molecular inhibitors appear to possess intrinsic antifungal activity and may therefore represent novel therapeutic options in future. This is particularly important given that antifungal resistance is a significant, emerging concern. This paper is a comprehensive review of the state-of-the-art in the molecular immunology to fungal pathogens as applied to existing and emerging small molecular inhibitors.

scholarly journals Targeted α particle immunotherapy for myeloid leukemia

Blood ◽  
2002 ◽  
Vol 100 (4) ◽  
pp. 1233-1239 ◽  
Author(s):  
Joseph G. Jurcic ◽  
Steven M. Larson ◽  
George Sgouros ◽  
Michael R. McDevitt ◽  
Ronald D. Finn ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myeloid Leukemia ◽  
Absorbed Dose ◽  
Myelogenous Leukemia ◽  
Whole Body ◽  
Hematopoietic Stem ◽  
Acute Myelogenous ◽  
Antigen System ◽  
High Doses ◽  
Nonspecific Cytotoxicity

Unlike β particle–emitting isotopes, α emitters can selectively kill individual cancer cells with a single atomic decay. HuM195, a humanized anti-CD33 monoclonal antibody, specifically targets myeloid leukemia cells and has activity against minimal disease. When labeled with the β-emitters 131I and 90Y, HuM195 can eliminate large leukemic burdens in patients, but it produces prolonged myelosuppression requiring hematopoietic stem cell transplantation at high doses. To enhance the potency of native HuM195 yet avoid the nonspecific cytotoxicity of β-emitting constructs, the α-emitting isotope 213Bi was conjugated to HuM195. Eighteen patients with relapsed and refractory acute myelogenous leukemia or chronic myelomonocytic leukemia were treated with 10.36 to 37.0 MBq/kg 213Bi-HuM195. No significant extramedullary toxicity was seen. All 17 evaluable patients developed myelosuppression, with a median time to recovery of 22 days. Nearly all the 213Bi-HuM195 rapidly localized to and was retained in areas of leukemic involvement, including the bone marrow, liver, and spleen. Absorbed dose ratios between these sites and the whole body were 1000-fold greater than those seen with β-emitting constructs in this antigen system and patient population. Fourteen (93%) of 15 evaluable patients had reductions in circulating blasts, and 14 (78%) of 18 patients had reductions in the percentage of bone marrow blasts. This study demonstrates the safety, feasibility, and antileukemic effects of 213Bi-HuM195, and it is the first proof-of-concept for systemic targeted α particle immunotherapy in humans.

scholarly journals Saponin Facilitates Anti-Robo1 Immunotoxin Cytotoxic Effects on Maxillary Sinus Squamous Cell Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Noriko Komatsu ◽  
Miku Komatsu ◽  
Riuko Ohashi ◽  
Akira Horii ◽  
Kazuto Hoshi ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Antibody Therapy ◽  
Suppressive Effect ◽  
Cytotoxic Effects ◽  
Specific Antigens ◽  
Nonspecific Cytotoxicity

Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide. The standard treatment of surgery, chemotherapy, and radiotherapy can result in long-term complications which lower the patient’s quality of life, such as eating disorders, speech problems, and disfiguring or otherwise untoward cosmetic issues. Antibody therapy against cancer-specific antigens is advantageous in terms of its lesser side effects achieved by its greater specificity, though the antitumor activity is still usually not enough to obtain a complete cure. Robo1, an axon guidance receptor, has received considerable attention as a possible drug target in various cancers. We have shown previously the enhanced cytotoxic effects of saporin-conjugated anti-Robo1 immunotoxin (IT-Robo1) on the HNSCC cell line HSQ-89 in combination with a photochemical internalization technique. Considering the light source, which has only limited tissue penetrance, we examined the drug internalization effect of saponin. Treatment with saponin facilitated significant cytotoxic effects of IT-Robo1 on HSQ-89 cells. Saponin exerts its own nonspecific cytotoxicity, which may cover the actual extent of the internalization effect. We thus examined whether a flashed treatment with saponin exerted a significant specific cytotoxic effect on cancer cells. The combination of an immunotoxin with saponin also exhibited a significant tumor-suppressive effect on mice HSQ-19 xenografts. These results suggest the utility of saponin treatment as an enhancer of immunotoxin treatment in cancer.

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