Oxidative Stress Therapy for Cancer Using Glycolysis Inhibitors: Towards Improving Therapeutic Outcomes

Abstract Background: Effective amelioration of neuronal damages in the case of cerebral ischemic stroke (CIS) is essential for the protection of brain tissues and their functional recovery. However, most drugs can not penetrate the blood-brain barrier (BBB), resulting in the poor therapeutic outcomes. Results: In this study, the derivatization and dual targeted delivery technologies were used to actively transport antioxidant melatonin (MLT) into the mitochondria of oxidative stress-damaged cells in brain tissues. A mitochondrial targeting molecule triphenylphosphine (TPP) was conjugated to melatonin (TPP-MLT) to increase the distribution of melatonin in intracellular mitochondria with the push of mitochondrial transmembrane potential. Then, TPP-MLT was encapsulated in dual targeted micelles mediated by TGN peptide (TGNYKALHPHNG) with high affinity for BBB and SHp peptide (CLEVSRKNG) for the glutamate receptor of oxidative stress-damaged neural cells.TGN/SHp/TPP-MLT micelles could effectively scavenge the overproduced ROS to protect neuronal cells from oxidative stress injury during CIS occurrence, as reflected by the improved infarct volume and neurological deficit in CIS model animals.Conclusions: These promising results showed this stepwise-targeting drug-loaded micelles potentially represent a significant advancement in the precise treatment of CIS.

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A stepwise-targeting strategy for the treatment of cerebral ischemic stroke

Journal of Nanobiotechnology ◽

10.1186/s12951-021-01118-6 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Jingbo Hu ◽

Xueying Tan ◽

Dongwei Wang ◽

Yixuan Li ◽

Hongze Liang ◽

...

Keyword(s):

Oxidative Stress ◽

Ischemic Stroke ◽

Targeted Delivery ◽

Infarct Volume ◽

Stress Injury ◽

Therapeutic Outcomes ◽

Cerebral Ischemic Stroke ◽

Cerebral Ischemic ◽

In Cis ◽

Brain Tissues

Abstract Background Effective amelioration of neuronal damages in the case of cerebral ischemic stroke (CIS) is essential for the protection of brain tissues and their functional recovery. However, most drugs can not penetrate the blood–brain barrier (BBB), resulting in the poor therapeutic outcomes. Results In this study, the derivatization and dual targeted delivery technologies were used to actively transport antioxidant melatonin (MLT) into the mitochondria of oxidative stress-damaged cells in brain tissues. A mitochondrial targeting molecule triphenylphosphine (TPP) was conjugated to melatonin (TPP-MLT) to increase the distribution of melatonin in intracellular mitochondria with the push of mitochondrial transmembrane potential. Then, TPP-MLT was encapsulated in dual targeted micelles mediated by TGN peptide (TGNYKALHPHNG) with high affinity for BBB and SHp peptide (CLEVSRKNG) for the glutamate receptor of oxidative stress-damaged neural cells.TGN/SHp/TPP-MLT micelles could effectively scavenge the overproduced ROS to protect neuronal cells from oxidative stress injury during CIS occurrence, as reflected by the improved infarct volume and neurological deficit in CIS model animals. Conclusions These promising results showed this stepwise-targeting drug-loaded micelles potentially represent a significant advancement in the precise treatment of CIS. Graphical Abstract

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Widening and Elaboration of Consecutive Research into Therapeutic Antioxidant Enzyme Derivatives

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/3075695 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Alexander V. Maksimenko

Keyword(s):

Oxidative Stress ◽

Endotoxin Shock ◽

Therapeutic Effects ◽

Vasoactive Agents ◽

Cardiovascular Damage ◽

Antioxidant Agents ◽

Antioxidative Stress ◽

Stress Therapy ◽

Insight Into

Undiminishing actuality of enzyme modification for therapeutic purposes has been confirmed by application of modified enzymes in clinical practice and numerous research data on them. Intravenous injection of the superoxide dismutase-chondroitin sulfate-catalase (SOD-CHS-CAT) conjugate in preventive and medicative regimes in rats with endotoxin shock induced with a lipopolysaccharide bolus has demonstrated that antioxidant agents not only effectively prevent damage caused by oxidative stress (as believed previously) but also can be used for antioxidative stress therapy. The results obtained emphasize the importance of investigation into the pathogenesis of vascular damage and the role of oxidative stress in it. The effects of intravenous medicative injection of SOD-CHS-CAT in a rat model of endotoxin shock have demonstrated a variety in the activity of this conjugate in addition to prevention of NO conversion in peroxynitrite upon interaction withO2∙-superoxide radical. Together with the literature data, these findings offer a prospect for the study of NO-independent therapeutic effects of SOD-CHS-CAT, implying the importance of a better insight into the mechanisms of the conjugate activity in modeled cardiovascular damage involving vasoactive agents other than NO.

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An NIR-II Responsive Nanoplatform for Cancer Photothermal and Oxidative Stress Therapy

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2021.751757 ◽

2021 ◽

Vol 9 ◽

Author(s):

Bin Huang ◽

Yuanpeng Huang ◽

Han Han ◽

Qiuyue Ge ◽

Dongliang Yang ◽

...

Keyword(s):

Oxidative Stress ◽

Photothermal Therapy ◽

Antitumor Effect ◽

Therapeutic Strategy ◽

Copper Ion ◽

Oxygen Species ◽

Intracellular Ros ◽

Stress Therapy ◽

Change Material ◽

And Oxidative Stress

Chemodynamic therapy as an emerging therapeutic strategy has been implemented for oncotherapy. However, the reactive oxygen species can be counteracted by the exorbitant glutathione (GSH) produced by the tumor cells before exerting the antitumor effect. Herein, borneol (NB) serving as a monoterpenoid sensitizer, and copper sulfide (CuS NPs) as an NIR-II photothermal agent were loaded in a thermo-responsive vehicle (NB/CuS@PCM NPs). Under 1,060-nm laser irradiation, the hyperthermia produced by CuS NPs can be used for photothermal therapy and melt the phase change material for drug delivery. In the acidity microenvironment, the CuS NPs released from NB/CuS@PCM NPs could degrade to Cu2+, then Cu2+ was reduced to Cu+ during the depletion of GSH. As Fenton-like catalyst, the copper ion could convert hydrogen peroxide into hydroxyl radicals for chemodynamic therapy. Moreover, the NB originated from NB/CuS@PCM NPs could increase the intracellular ROS content to improve the treatment outcome of chemodynamic therapy. The animal experimental results indicated that the NB/CuS@PCM NPs could accumulate at the tumor site and exhibit an excellent antitumor effect. This work confirmed that the combination of oxidative stress–induced damage and photothermal therapy is a potential therapeutic strategy for cancer treatment.

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Influence of GSTM1, GSTT1, and GSTP1 genetic polymorphisms on disorders in transplant patients: a systematic review

Drug Metabolism and Personalized Therapy ◽

10.1515/dmpt-2021-0165 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Murilo Pita-Oliveira ◽

Fernanda Rodrigues-Soares

Keyword(s):

Oxidative Stress ◽

Systematic Review ◽

Glutathione S Transferase ◽

Transplant Patients ◽

Enzymatic Function ◽

Therapeutic Outcomes ◽

Pubmed Database ◽

Genes Encoding ◽

Repair Ability ◽

Gst Family

Abstract The glutathione-S-transferase (GST) enzymes are phase II isoenzymes responsible for protection against free radicals and xenobiotics. Since these proteins are described as polymorphic, polymorphisms in genes that encode them may alter enzymatic function and contribute to oxidative stress. In this context, such polymorphisms were already associated with several diseases and multiple therapeutic outcomes. A systematic review was performed to evaluate studies regarding the association between polymorphisms in three genes encoding enzymes of the GST family – GSTM1, GSTT1, and GSTP1 – and disorders in transplant patients. A total of 125 articles on which inclusion and exclusion criteria were applied were identified at PubMed database. Thirty-two studies met the target criteria and were included in the review. The mechanisms by which GST genotypes influence the development of disorders in transplant patients differ by disorder: they may participate in it by decreasing metabolism of drugs administered to patients undergoing transplantation, then exposing them to greater toxicity; by decreasing the repair ability against oxidative stress; or by encoding proteins that may be recognized as foreign, setting of an alloimmune reaction. Although some results are better established – such as GSTM1 null genotype’s role in the development of toxicity events in transplant patients – others require further evidences, as GST influence on the development of pulmonary decline and posttransplant diabetes mellitus (PTDM). The importance of investigating these associations lies in a personalized medicine, in which the high-risk genotype patient has its treatment individualized and its care for prophylaxis and surveillance increased, potentially reducing this population’s morbimortality.

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Oxidative stress therapy for solid tumors – A proposal

Medical Hypotheses ◽

10.1016/j.mehy.2009.12.029 ◽

2010 ◽

Vol 74 (6) ◽

pp. 1052-1054 ◽

Cited By ~ 16

Author(s):

Mark F. McCarty ◽

Jorge Barroso-Aranda ◽

Francisco Contreras

Keyword(s):

Oxidative Stress ◽

Solid Tumors ◽

Stress Therapy

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Combined Efficacy of Gallic Acid and MiADMSA with Limited Beneficial Effects over MiADMSA against Arsenic-induced Oxidative Stress in Mouse

Biochemistry Insights ◽

10.4137/bci.s30505 ◽

2015 ◽

Vol 8 ◽

pp. BCI.S30505 ◽

Cited By ~ 10

Author(s):

Vidhu Pachauri ◽

S.J.S. Flora

Keyword(s):

Oxidative Stress ◽

Organic Acid ◽

Gallic Acid ◽

Therapeutic Efficacy ◽

Arsenic Exposure ◽

Beneficial Effects ◽

Anticancer Properties ◽

Therapeutic Outcomes ◽

Higher Doses

Gallic acid is an organic acid known for its antioxidant and anticancer properties. The present study is focused on evaluating the role of gallic acid in providing better therapeutic outcomes against arsenic-induced toxicity. Animals pre-exposed to arsenic were treated with monoisoamyl meso-2,3-dimercaptosuccinic acid (MiADMSA), a new chelating drug, alone and in combination with gallic acid, consecutively for 10 days. The study suggests that (1) gallic acid in presence of MiADMSA is only moderately beneficial against arsenic, (2) monotherapy with gallic acid is more effective than in combination with MiADMSA after arsenic exposure in reducing oxidative injury, and (3) MiADMSA monotherapy as reported previously provides significant therapeutic efficacy against arsenic. Thus, based on the present results, we conclude that gallic acid is effective against arsenic-induced oxidative stress but provides limited additional beneficial effects when administered in combination with MiADMSA. We still recommend that lower doses of gallic acid be evaluated both individually and in combination with MiADMSA, as it might not exhibit the shortcomings we observed with higher doses in this study.

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Attenuation of Oxidative Stress by Cannabinoids and Cannabis Extracts in Differentiated Neuronal Cells

Pharmaceuticals ◽

10.3390/ph13110328 ◽

2020 ◽

Vol 13 (11) ◽

pp. 328

Author(s):

Aruna Raja ◽

Soha Ahmadi ◽

Fernanda de Costa ◽

Nan Li ◽

Kagan Kerman

Keyword(s):

Oxidative Stress ◽

Antioxidant Activity ◽

Neuronal Cells ◽

In Vitro Models ◽

Proof Of Concept ◽

In Vitro System ◽

Pathological Conditions ◽

Stress Therapy ◽

Antagonist Effect

In this proof-of-concept study, the antioxidant activity of phytocannabinoids, namely cannabidiol (CBD) and Δ9- tetrahydrocannabinol (THC), were investigated using an in vitro system of differentiated human neuronal SY-SH5Y cells. The oxidative stress was induced by hydrogen peroxide, as reactive oxygen species (ROS). Alzheimer’s disease (AD)-like pathological conditions were mimicked in vitro by treating the differentiated neuronal cells with amyloid-β1–42 (Aβ1–42) in the presence of Cu(II). We showed that THC had a high potency to combat oxidative stress in both in vitro models, while CBD did not show a remarkable antioxidant activity. The cannabis extracts also exhibited a significant antioxidant activity, which depended on the ratio of the THC and CBD. However, our results did not suggest any antagonist effect of the CBD on the antioxidant activity of THC. The effect of cannabis extracts on the cell viability of differentiated human neuronal SY-SH5Y cells was also investigated, which emphasized the differences between the bioactivity of cannabis extracts due to their composition. Our preliminary results demonstrated that cannabis extracts and phytocannabinoids have a promising potential as antioxidants, which can be further investigated to develop novel pharmaceuticals targeting oxidative stress therapy.

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Amplified Oxidative Stress Therapy of Degradable Copper Phosphate Nanozyme Coated by in situ Polymerization of PEGDA

Journal of Materials Chemistry B ◽

10.1039/d1tb00436k ◽

2021 ◽

Author(s):

Ning Nie ◽

Yifan Liu ◽

Bing Li ◽

Zhentao Hua ◽

Jianfeng Liu ◽

...

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

In Situ Polymerization ◽

Reactive Oxygen ◽

Oxygen Species ◽

First Report ◽

Copper Phosphate ◽

Stress Therapy

Elimination of reactive oxygen species (ROS) caused by glutathione (GSH) is a fundamental concern in oxidative stress therapy (OST) of tumors. This is the first report of copper phosphate nanospheres...

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