Melatonin: reducing the toxicity and increasing the efficacy of drugs

Journal of Pharmacy and Pharmacology, Journal Year: 2002, Volume and Issue: 54(10), P. 1299 - 1321

Published: Oct. 1, 2002

Melatonin (N-acetyl-5-methoxytryptamine) is a molecule with very wide phylogenetic distribution from plants to man. In vertebrates, melatonin was initially thought be exclusively of pineal origin recent studies have shown, however, that synthesis may occur in variety cells and organs. The concentration within body fluids subcellular compartments varies widely, blood levels the indole being lower than those at many other sites. Thus, when defining what constitutes physiological level melatonin, it must defined relative specific compartment. has been shown functions, research last decade proven both direct free radical scavenger indirect antioxidant. Because these actions, possibly others remain defined, reduce toxicity increase efficacy large number drugs whose side effects are well documented. Herein, we summarize beneficial combined following drugs: doxorubicin, cisplatin, epirubicin, cytarabine, bleomycin, gentamicin, ciclosporin, indometacin, acetylsalicylic acid, ranitidine, omeprazole, isoniazid, iron erythropoietin, phenobarbital, carbamazepine, haloperidol, caposide-50, morphine, cyclophosphamide L-cysteine. While majority were conducted using animals, investigations also used Considering low its ability drugs, use as combination therapy agents seems important worthy pursuit.

Language: Английский

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Neuroprotection in Relation to Retinal Ischemia and Relevance to Glaucoma

Survey of Ophthalmology, Journal Year: 1999, Volume and Issue: 43, P. S102 - S128

Published: June 1, 1999

Language: Английский

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Melatonin receptors, heterodimerization, signal transduction and binding sites: what's new?

British Journal of Pharmacology, Journal Year: 2008, Volume and Issue: 154(6), P. 1182 - 1195

Published: May 20, 2008

Melatonin is a neurohormone that has been claimed to be involved in wide range of physiological functions. Nevertheless, for most its effects, the mechanism action not really known. In mammals, two melatonin receptors, MT1 and MT2, have cloned. They belong G-protein-coupled receptor (GPCR) superfamily. share some specific short amino-acid sequences, which suggest they represent subfamily. Another from same subfamily, melatonin-related cloned different species including humans. This orphan also named GPR50 does bind endogenous ligand still unknown. this shown behave as an antagonist receptor, opens new pharmacological perspectives despite lack or synthetic ligands. Moreover, MT2 interact together through formation heterodimers at least cells transfected with cDNA these receptors. Lastly, signalling complexes associated receptors are starting deciphered. A third melatonin-binding site purified characterized enzyme quinone reductase 2 (QR2). Inhibition QR2 by may explain melatonin's protective effect reported animal models generally well-documented antioxidant properties.

Language: Английский

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Radiations and male fertility

Reproductive Biology and Endocrinology, Journal Year: 2018, Volume and Issue: 16(1)

Published: Nov. 16, 2018

During recent years, an increasing percentage of male infertility has to be attributed array environmental, health and lifestyle factors. Male is likely affected by the intense exposure heat extreme pesticides, radiations, radioactivity other hazardous substances. We are surrounded several types ionizing non-ionizing radiations both have recognized causative effects on spermatogenesis. Since it impossible cover all radiation sources their biological under a single title, this review focusing deriving from cell phones, laptops, Wi-Fi microwave ovens, as these most common which may contribute cause exploring effect radiofrequency fertility pattern. From currently available studies clear that electromagnetic fields (RF-EMF) deleterious sperm parameters (like count, morphology, motility), affects role kinases in cellular metabolism endocrine system, produces genotoxicity, genomic instability oxidative stress. This followed with protective measures for future recommendations. The study concludes RF-EMF induce stress increased level reactive oxygen species, lead infertility. been concluded based evidences vitro vivo suggesting negatively quality.

Language: Английский

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Nanozymatic Antioxidant System Based on MoS₂ Nanosheets

ACS Applied Materials & Interfaces, Journal Year: 2018, Volume and Issue: 10(15), P. 12453 - 12462

Published: March 29, 2018

The enzymatic antioxidant system (EAS) protects aerobic cells from oxidative stress. However, it is brittle and susceptible of inactivation reactive oxygen species (ROS) immoderate production. Here, we demonstrated that MoS2 nanosheets (few-layer MoS2), as a multifunctional nanozyme, possess intrinsic activity mimicking enzymes superoxide dismutases (SODs), catalases (CATs), peroxidases (PODs) under physiological conditions (pH 7.4, 25 °C). Further, showed POD-like by transferring electrons instead generating ROS. Similar to EAS, defense termed nanozymatic (NAS) was developed nanosheets, for regulation Surprisingly, this NAS can effectively scavenge other free radicals including hydroxyl (•OH), nitrogen-centered (•DPPH), nitric oxide (•NO). To evaluate these unique properties MoS2-based in vivo, Escherichia coli ( E. coli), Staphylococcus aureus S. aureus), A549 cell models were established, respectively. These results superiorly protect bacteria against injury caused H2O2. This work makes promising antioxidants the pathological processes expands their application biocatalysis nano-biomedicine.

Language: Английский

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Critical role of AMPK in redox regulation under glucose starvation

Redox Biology, Journal Year: 2019, Volume and Issue: 25, P. 101154 - 101154

Published: March 2, 2019

Glucose starvation is one of the major forms metabolic stress in cancer cells. Deprivation glucose impairs glycolysis and pentose phosphate pathway, which elicits oxidative due to enhanced production reactive oxygen species (ROS) impaired antioxidant system, leading redox imbalance cell death. Under starvation, 5′ AMP-activated protein kinase (AMPK) plays a critical role maintaining homeostasis survival via multiple pathways, such as regulation fatty acid metabolism response. Convergence ROS pathway reveals novel molecular targets for development effective therapeutic strategies. Interestingly, AMPK, along with its upstream liver B1 (LKB1), has been regarded play tumor suppressor role. However, emerging studies have provided insights into pro-tumor function LKB1-AMPK pathway. Therefore, targeting cells, manipulation AMPK activity, promising strategy developing agents.

Language: Английский

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Bacterial Response to Oxidative Stress and RNA Oxidation

Frontiers in Genetics, Journal Year: 2022, Volume and Issue: 12

Published: Jan. 10, 2022

Bacteria have to cope with oxidative stress caused by distinct Reactive Oxygen Species (ROS), derived not only from normal aerobic metabolism but also oxidants present in their environments. The major ROS include superoxide O2-, hydrogen peroxide H2O2 and radical hydroxide HO•. To protect cells under stress, bacteria induce the expression of several genes, namely SoxRS, OxyR PerR regulons. Cells are able tolerate a certain number free radicals, high levels result oxidation biomolecules. Strikingly, RNA is particularly susceptible this common chemical damage. Oxidation causes formation strand breaks, elimination bases or insertion mutagenic lesions nucleobases. most modification 8-hydroxyguanosine (8-oxo-G), an oxidized form guanosine. structure function virtually all species (mRNA, rRNA, tRNA, sRNA) can be affected oxidation, leading translational defects harmful consequences for cell survival. However, evolved quality control pathways eliminate RNA, involving RNA-binding proteins like members MutT/Nudix family ribonuclease PNPase. Here we summarize current knowledge on bacterial response different responsible damage describe main strategies employed fight

Language: Английский

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Sequential Therapy for Bone Regeneration by Cerium Oxide-Reinforced 3D-Printed Bioactive Glass Scaffolds

ACS Nano, Journal Year: 2023, Volume and Issue: 17(5), P. 4433 - 4444

Published: Feb. 20, 2023

Rational design of multifunctional biomaterials with customized architecture and on demand bioactivity is great significance for bone tissue engineering (BTE) in modern society. Herein, a versatile therapeutic platform has been established by integrating cerium oxide nanoparticles (CeO2 NPs) into bioactive glass (BG) to fabricate three-dimensional (3D)-printed scaffolds, achieving sequential effect against inflammation promoting osteogenesis toward defect. The antioxidative activity CeO2 NPs plays crucial role alleviating the oxidative stress upon formation defects. Subsequently, exert promotion proliferation osteogenic differentiation rat osteoblasts through enhancing mineral deposition alkaline phosphatase gene expression. Strikingly, incorporation bestows BG scaffolds greatly reinforced mechanical properties, improved biocompatibility, adequate cell adhesion, elevated capability, performance single platform. In vivo studies treatment tibial defect confirmed better properties CeO2-BG compared pure scaffolds. Additionally, employment 3D printing technique creates proper porous microenvironment around defect, which further facilitates in-growth new formation. This report provides systematic study 3D-printed prepared simple ball milling method, integral BTE based

Language: Английский

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Melatonin: From Basic Research to Cancer Treatment Clinics

Journal of Clinical Oncology, Journal Year: 2002, Volume and Issue: 20(10), P. 2575 - 2601

Published: May 15, 2002

ABSTRACT: Melatonin, the chief secretory product of pineal gland, is a direct free radical scavenger, an indirect antioxidant, as well important immunomodulatory agent. In both in vitro and vivo investigations, melatonin protected healthy cells from radiation-induced chemotherapeutic drug–induced toxicity. Furthermore, several clinical studies have demonstrated potential melatonin, either alone or combination with traditional therapy, to yield favorable efficacy toxicity ratio treatment human cancers. This study reviews literature laboratory investigations that document antioxidant oncostatic actions summarizes evidence regarding use cancer treatment. also provides rationale for design larger translational research–based trials.

Language: Английский

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Melatonin but not vitamins C and E maintains glutathione homeostasis in t‐butyl hydroperoxide‐induced mitochondrial oxidative stress

The FASEB Journal, Journal Year: 2000, Volume and Issue: 14(12), P. 1677 - 1679

Published: July 24, 2000

Mitochondria do not contain catalase and are therefore largely dependent on reduced glutathione (GSH) peroxidases for its antioxidant protection. When GSH levels greatly decreased, hydrogen peroxide accumulates leading to extensive mitochondrial damage. Melatonin has properties prevents toxic effects of reactive oxygen species by maintaining cellular homeostasis. Thus, we examined the influence melatonin other classical antioxidants such as vitamins C E content activity GSH-related enzymes (glutathione peroxidase reductase) in isolated rat liver brain mitochondria treated with t-butyl hydroperoxide (i-BHP). In control (100 nM) significantly increases reductase activities. After incubation 100 μM i-BHP, hydroperoxides level increased, 90% was oxidized GSSH, activities were almost totally inhibited. counteracted changes GSH, induced i-BHP cultured mitochondria. presence nM melatonin, respiratory chain complexes I IV, measured submitochondrial particles prepared from mitochondria, increased significantly. Vitamin virtually without effect, only 1 mM vitamin contents. Our results suggest that but E, regenerating their content.

Language: Английский

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