Search Results (70)

Despite significant advancement in cancer treatments, therapies with minimal toxicity to healthy cells are still limited. One targetable weakness of cancer cells is their sensitivity to oxidative stress. We find that the combination of two antioxidants—the common food additive tert-butylhydroquinone (tBHQ) and a manganese porphyrin in clinical trials, MnTnBuOE-2-PyP⁵⁺ (MnBuOE)—increases oxidative stress and causes apoptotic death in several cancer cell lines, but not in mouse primary fibroblasts. Investigating the mechanism of cell death, MnBuOE is observed to catalyze the oxidation of tBHQ, producing the electrophilic quinone tert-butylquinone (tBQ). A critical role for tBQ and its electrophilic character was revealed with the observation that di-tert-butylhydroquinone (dtBHQ) in combination with MnBuOE causes no observable oxidative stress and is non-toxic, despite rapid oxidation to di-tert-butylquinone (dtBQ), a non-electrophilic quinone. Cell death from the combination of tBHQ and MnBuOE appears to be completely dependent on the generation of hydrogen peroxide, as shown by the inclusion of catalase. This system, in which two non-toxic molecules in combination cause specific toxicity to cancer cells, is a potential means to kill cancer cells in a targeted manner. Full article

This work presents the design of a novel electrochemical sensor for highly sensitive determination of LEV, utilizing a sensing platform based on a newly synthesized, high-purity manganese (III) porphyrin complex [5,10,15,20-tetrayltetrakis(2-methoxybenzene-4,1-diyl) tetraisonicotinateporphyrinato] manganese (III) porphyrin (MnTMIPP). The successful synthesis of the MnTMIPP complex was verified using ultraviolet–visible (UV–Vis) and infrared spectroscopy (IR). The sensing electrode was fabricated by depositing the synthesized material onto an indium tin oxide (ITO) electrode via a drop-coating method. Under optimized experimental conditions, the proposed sensor demonstrated a wide dynamic range, from 10⁻⁹ M to 10⁻³ M, with a low calculated detection limit of 4.82 × 10⁻¹⁰ M. Furthermore, the MnTMIPP/ITO electrode displayed interesting metrological performance: high selectivity, reproducibility, and stability. Successful application in spiked river water and saliva samples with satisfactory recovery rates confirms the sensor’s potential as a reliable and cost-effective platform for monitoring LEV in real-world environments. Full article

Background: The combination of manganese porphyrins (MnPs) and ascorbate (ASC) represents a promising redox-based therapeutic approach for selectively targeting cancer cells. We investigated the cytotoxic effects of two structurally distinct MnPs (MnTPPS and MnF₂BMet) with differing lipophilicity and potential membrane permeability in combination with ASC. Methods: Cancer cell lines (MCF-7, PANC-1, U87, T98G, AT-2) and normal human dermal fibroblasts (HDFs) were treated with MnTPPS and MnF₂BMet in the absence or presence of ASC. Viability, migration potential, and intracellular oxidative stress were assessed using single-cell methods. Results: MnPs alone exhibited no intrinsic cytostatic or cytotoxic activity, as confirmed by proliferation, viability, and motility assays. When combined with ASC, both MnTPPS and MnF₂BMet significantly enhanced ASC-induced oxidative stress, leading to lipid peroxidation, glutathione depletion, mitochondrial dysfunction, and cell membrane disruption. Time-lapse microscopy revealed rapid necrotic cell death under co-treatment. Catalase fully abolished cytotoxicity, indicating the essential role of hydrogen peroxide. In contrast, dehydroascorbate (DHA), which increases intracellular ASC levels, did not induce the same toxicity, suggesting that extracellular ROS generation contributes predominantly to the observed effects. Normal fibroblasts were minimally affected, supporting the MnPs–ASC system’s selectivity toward cancer cells. Conclusions: MnTPPS and MnF₂BMet enhance extracellular oxidation of ascorbate and subsequent ROS production, leading to selective oxidative-stress-mediated cancer cell death. This study supports the potential of MnPs–ASC redox catalysis as a complementary oxidative-stress-based anticancer strategy and highlights the need for further mechanistic and structure–activity investigations. Full article

Reactive oxygen species (ROS) function as critical signaling molecules in cancer biology, promoting proliferation, angiogenesis, and metastasis at controlled levels while inducing lethal damage when exceeding the cell’s buffering capacity. To survive under this state of chronic oxidative stress, cancer cells become dependent on a hyperactive antioxidant shield, primarily orchestrated by the Nrf2, glutathione (GSH), and thioredoxin (Trx) systems. These defenses maintain redox homeostasis and sustain oncogenic signaling, notably through the oxidative inactivation of tumor-suppressor phosphatases, such as PTEN, which drives the PI3K/AKT/mTOR pathway. Targeting this addiction to a rewired redox state has emerged as a compelling therapeutic strategy. Pro-oxidant therapies aim to overwhelm cellular defenses, with agents like high-dose vitamin C and arsenic trioxide (ATO) showing significant tumor-selective toxicity. Inhibiting the master regulator Nrf2 with compounds such as Brusatol or ML385 disrupts the core antioxidant response. Disruption of the GSH system by inhibiting cysteine uptake with sulfasalazine or erastin potently induces ferroptosis, a non-apoptotic cell death driven by lipid peroxidation. Furthermore, the thioredoxin system is targeted by the repurposed drug auranofin, which irreversibly inhibits thioredoxin reductase (TrxR). Extensive preclinical data and ongoing clinical trials support the concept that this reliance on redox adaptation is a cancer-selective vulnerability. Moreover, novel therapeutic strategies, including the expanding field of redox-active metal complexes, such as manganese porphyrins, which strategically leverage the differential redox state of normal versus cancer cells through both pro-oxidant and indirect Nrf2-mediated antioxidative mechanisms (triggered by Keap1 oxidation), with several agents currently in advanced clinical trials, have also been discussed. Essentially, pharmacologically tipping the redox balance beyond the threshold of tolerance offers a rational and powerful approach to eliminate malignant cells, defining a novel frontier for targeted cancer therapy. Full article

Oxidative stress and mitochondrial dysfunction are heavily implicated in all forms of Parkinson’s disease; however, antioxidant administration has largely failed in clinical trials. Among the likely causes of failure are brain bioavailability and cellular redox state. We have administered two manganese porphyrin compounds with different bioavailability, MnTE-2-PyP⁵⁺ and MnTnBuOE-2-PyP⁵⁺, to parkin-null Drosophila food and found that the more bioavailable one, with higher brain and mitochondrial availability, MnTnBuOE-2-PyP⁵⁺, improves developmental deficits and motivated behavior in female flies. Using highly sensitive redox reporters, we further found that MnTnBuOE-2-PyP⁵⁺ reduces hydrogen peroxide levels in mitochondria of dopaminergic neurons that are functionally homologous to the mammalian substantia nigra and facilitates motivated behavior in female flies. Interestingly, both compounds reduce an oxidative stress marker at the whole-brain level and extend lifespan in control flies. Neither compound improves lifespan in parkin-null flies. Thus, additional studies, changing the timing and/or dosage of compound administration, are warranted. Full article

In the present work, meso-tetrakis(2,4,6-trimethylphenyl) porphyrinato)zinc(II): ([Zn(TMP)] (1), meso-tetrakis-(tetraphenyl)porphyrin iron(III))chloride): [Fe(TPP)Cl] (2), and meso-tetrakis(phenyl)porphyrin manganese(III) chloride): [Mn(TPP)Cl] (3) were synthesized. Then, the three prepared porphyrinic complexes (1–3) were functionalized with branched polyethyleneimine (PEI). The prepared complexes were thoroughly analyzed using several analytical techniques, including ¹H NMR, FT-IR, UV-vis, XRD, XRF, TGA-DTA, SEM, and EDX. The presence of sharp main peaks at 2θ between 10° and 80°, in XRD analysis, for all studied compounds suggested the crystalline nature of the porphyrinic complexes. The morphological properties of the porphyrininc complexes were significantly affected by the chemical modification with polyethyleneimine. EDX result confirmed the complexation of zinc, iron, and manganese metals with the porphyrinic core. The increase in carbon and nitrogen contents after the addition of polyethyleneimine to the complexes (1–3) was noticeable. After thermal decomposition, the total mass loss was equal to 92.97%, 66.77%, and 26.78% for complexes (1), (2), and (3), respectively. However, for the complex (1)-PEI, complex (2)-PEI, and complex (3)-PEI, the total mass losses were 83.12%, 81.88%, and 35.78%, respectively. The synthetic compounds were additionally utilized for the adsorption of Naphthol blue black B from water. At optimum adsorption conditions (T = 20 °C, time = 60 min, pH = 5), the highest adsorption capacities were 154 mg/g, 139 mg/g, and 119 mg/g for complex (3)-PEI, complex (2)-PEI, and complex (1)-PEI, respectively. The adsorption mechanism followed the pseudo second order, the Freundlich, and the Temkin models. The results indicated that the adsorption process is reliant on chemical interactions. It was also governed by intraparticular diffusion and other kinetic phenomena. Full article

There is increasing interest in identifying drugs that can prevent or delay neurological complications following spinal cord injury, thus expanding the therapeutic window for other potential neuroprotective agents. In this context, manganese porphyrins (MnPs) have shown high antioxidant and anti-inflammatory potential in various experimental disease models, including stroke, cancer, diabetes, ischemia, and radiotherapy. However, they have been little evaluated in spinal cord injuries. This study aimed to assess the therapeutic potential of the manganese porphyrins [MnTE-2-PyP]⁵⁺ (MnPI) and [MnT(5-Br-3-E-Py)P]⁵⁺ (MnPII) in acute compressive spinal cord trauma in rats. Twenty-four animals were used (six animals/group). Following general inhalation anesthesia, acute compressive spinal cord trauma was induced in all groups except for the negative control (SHAM). Treatment commenced 60 min post-trauma, with animals receiving treatment for seven days at 24 h intervals. While no improvement in motor capacity was observed, MnPs effectively blocked the increase in oxidative stress and endoplasmic reticulum (ER) stress mediators caused by trauma, maintaining the protein expression levels of Hifα, 8-OHdG and MDA, as well as the expression of the genes Grp78, Chop, Ho1, and Perk, similar to those of the control group. Moreover, there was an increase in protein expression of SOD1, Cat, and GPX1, along with a restoration of SOD and CAT enzymatic activity. Additionally, MnPs improved the expression of IL-6, neurotrophic markers, and apoptotic factors. In conclusion, treatment with MnPs attenuated the oxidative stress and ER stress caused by acute compressive spinal cord trauma and restored spinal expression of neurotrophic mediators. Full article

The optical detection of thioacetamide was investigated using a metalated porphyrin, Mn(III)-5,10,15,20-tetrakis-(3,4-dimethoxyphenyl)-21H,23H-porphyrin chloride (Mn-3,4-diMeOPP), a gold colloid solution (AuNPs), and a complex formed between them (Mn-3,4-diMeOPP–AuNPs) in order to select the most sensitive material and to achieve complementarity between methods. Mn-3,4-diMeOPP, AuNPs, and their complex were synthesized and characterized by means of UV–Vis, FT-IR spectrometry, and AFM investigations. It could be concluded that Mn-3,4-diMeOPP could detect/quantify thioacetamide (TAA) in the range 3.13 × 10⁻⁸ M–7.67 × 10⁻⁷ M in a linear fashion, with a 99.85% confidence coefficient. The gold colloidal particles alone could detect TAA in an extremely narrow concentration domain of 2–9.8 × 10⁻⁷ M, slightly complementary with that of Mn-3,4-diMeOPP. The complex between Mn-3,4-diMeOPP and gold colloid proved to be able to quantify TAA in the trace domain with concentrations of 1.99 × 10⁻⁸ M–1.76 × 10⁻⁷ M in a polynomial fashion, with the method being more difficult. A potential mechanism for TAA detection based on Mn-3,4-diMeOPP is discussed based on computational modeling. The distorted porphyrin conformation and its electronic configuration favor the generation of a grid of electrostatic interactions between porphyrin and TAA. Full article

Background: Manganese porphyrin, MnTnBuOE-2-PyP⁵⁺ (BMX-001), improves neurologic deficits in experimental ischemic stroke and has the potential to serve as an adjunct with thrombolysis or thrombectomy in stroke patients. In 10–30% of stroke patients following thrombolysis, the hemorrhagic transformation, associated with iron release, occurs. This study aimed to examine the neurologic outcome following the BMX-001 treatment in a mouse intracerebral hemorrhage (ICH) model with relevance to prospective ischemic stroke clinical trials. Methods: Twenty C57Bl6 mice were randomly assigned to groups after surgery and received vehicle or BMX-001 treatment immediately following stereotaxic left striatum collagenase injection. Post-ICH body weight, the Corner test, neurological deficit score, and Rotarod test were examined. Six sham surgery mice serve as a control group. At 72 h, the brain histological evaluation was performed, including hemorrhage size, Prussian blue staining, and the activation of macrophages. Data were collected by a researcher who was blind to groups. Results: No significant difference in body weight, neurological deficits, and hemorrhage size was found between groups. However, BMX-001 reduced the number of macrophages in the hemorrhagic area (48 ± 10 in vehicle, 33 ± 8 in BMX-001, p = 0.008) and the number of cells stained with Prussian blue—an indicator of iron released during hemorrhage (65 ± 22 in vehicle and 41 ± 15 in BMX-001, p = 0.027). Conclusions: The results support the safe use of BMX-001 in stroke patients in combination with thrombolysis or thrombectomy and, moreover, indicate the beneficial anti-inflammatory effect of BMX-001, alike to that previously reported in stroke studies of analogous, similarly redox-active, Mn porphyrins. Full article

Neuropathic pain, a debilitating condition arising from somatosensory system damage, significantly impacts quality of life, leading to anxiety, self-mutilation, and depression. Oxidative and nitrosative stress, an imbalance between reactive oxygen and nitrogen species (ROS/RNS) and antioxidant defenses, plays a crucial role in its pathophysiology. While reactive species are essential for physiological functions, excessive levels can cause cellular component damage, leading to neuronal dysfunction and pain. This review highlights the complex interactions between reactive species, antioxidant systems, cell signaling, and neuropathic pain. We discuss the physiological roles of ROS/RNS and the detrimental effects of oxidative and nitrosative stress. Furthermore, we explore the potential of manganese porphyrins, compounds with antioxidant properties, as promising therapeutic agents to mitigate oxidative stress and alleviate neuropathic pain by targeting key cellular pathways involved in pain. Further research is needed to fully understand their therapeutic potential in managing neuropathic pain in human and non-human animals. Full article

Reactive oxygen species (ROS) are double-edged swords in biological systems—they are essential for normal cellular functions but can cause damage when accumulated due to oxidative stress. Manganese superoxide dismutase (MnSOD), located in the mitochondrial matrix, is a key enzyme that neutralizes superoxide radicals (O₂^•−), maintaining cellular redox balance and integrity. This review examines the development and therapeutic potential of MnSOD mimetics—synthetic compounds designed to replicate MnSOD’s antioxidant activity. We focus on five main types: Mn porphyrins, Mn salens, MitoQ10, nitroxides, and mangafodipir. These mimetics have shown promise in treating a range of oxidative stress-related conditions, including cardiovascular diseases, neurodegenerative disorders, cancer, and metabolic syndromes. By emulating natural antioxidant defenses, MnSOD mimetics offer innovative strategies to combat diseases linked to mitochondrial dysfunction and ROS accumulation. Future research should aim to optimize these compounds for better stability, bioavailability, and safety, paving the way for their translation into effective clinical therapies. Full article

In the current work, chloro(meso-tetrakis(phenyl)porphyrin) manganese(III) [Mn(TPP)Cl] was synthesized following two steps: the preparation of meso-tetraphenylporphyrin (H_⁠2TPP) and the insertion of manganese into the free porphyrin H₂TPP. The compounds were characterized using SEM, FT-IR, UV, TGA/DTA, and XRD analyses. Manganese(III) meso-porphyrins exhibited hyper-type electronic spectra with a half-vacant metal orbital with symmetry, such as [dπ:dxz and dyz]. The thermal behavior of [Mn(TPP)(Cl)] changed (three-step degradation process) compared to the initial H₂TPP (one-step degradation process), confirming the insertion of manganese into the core of the free porphyrin H₂TPP. Furthermore, [Mn(TPP)Cl] was used to degrade calmagite (an azo dye) using H₂O₂ as an oxidant. The effects of dye concentration, reaction time, H₂O₂ dose, and temperature were investigated. The azo dye solution was completely degraded in the presence of [Mn(TPP)(Cl)]/H₂O₂ at pH = 6, temperature = 20 °C, C₀ = 30 mg/L, and H₂O₂ = 40 mL/L. The computed low activation energy (Ea = 10.55 Kj/mol) demonstrated the efficiency of the proposed catalytic system for the azo dye degradation. Overall, based on the synthesis process and the excellent catalytic results, the prepared [Mn(TPP)Cl] could be used as an effective catalyst for the treatment of calmagite-contaminated effluents. Full article

A paramagnetic A₃B-type Mn(III)-porphyrin was synthesized and characterized by physical–chemical methods (UV-Vis, FT-IR, ¹H-NMR spectroscopy). The obtained compound was tested as a sensitive material for the spectrophotometric and potentiometric detection of iodine species. Using UV-Vis spectroscopy, the triiodide anions could be detected with high precision in the concentration interval of 1.02 × 10⁻⁵ to 2.3 × 10⁻⁵ M, with an LOD of 9.44 × 10⁻⁶ M. The PVC-based electrode using DOP as a plasticizer showed a sensitivity toward iodide in a wide concentration range of 1.0 × 10⁻⁵ to 1.0 × 10⁻¹ M, with an LOD of 8.0 × 10⁻⁶ M. Both methods are simple, low-cost, and efficient for the detection of iodine species in synthetic samples and pharmaceuticals. Full article

Morphine is an important pain reliever employed in pain management, its extended utilize is hindered by the onset of analgesic tolerance and oxidative stress. Long-term morphine administration causes elevated production of reactive oxygen species (ROS), disrupting mitochondrial function and inducing oxidation. Sirtuin 3 (SIRT3), a mitochondrial protein, is essential in modulating ROS levels by regulating mitochondrial antioxidant enzymes as manganese superoxide dismutase (MnSOD). Our investigation focused on the impact of SIRT3 on hyperalgesia and morphine tolerance in mice, as evaluating the antioxidant effect of the polyphenolic fraction of bergamot (BPF). Mice were administered morphine twice daily for four consecutive days (20 mg/kg). On the fifth day, mice received an acute dose of morphine (3 mg/kg), either alone or in conjunction with BPF or Mn (III)tetrakis (4-benzoic acid) porphyrin (MnTBAP). We evaluated levels of malondialdehyde (MDA), nitration, and the activity of SIRT3, MnSOD, glutamine synthetase (GS), and glutamate 1 transporter (GLT1) in the spinal cord. Our findings demonstrate that administering repeated doses of morphine led to the development of antinociceptive tolerance in mice, accompanied by increased superoxide production, nitration, and inactivation of mitochondrial SIRT3, MnSOD, GS, and GLT1. The combined administration of morphine with either BPF or MnTBAP prevented these effects. Full article

Efforts have been made to improve the therapeutic efficiency of tumor treatments, and metal-organic frameworks (MOFs) have shown excellent potential in tumor therapy. Monotherapy for the treatment of tumors has limited effects due to the limitation of response conditions and inevitable multidrug resistance, which seriously affect the clinical therapeutic effect. In this study, we chose to construct a multiple cascade synergistic tumor drug delivery system MIL−101(Fe)−DOX−TCPP−MnO₂@PDA−Ag (MDTM@P−Ag) using MOFs as drug carriers. Under near-infrared (NIR) laser irradiation, 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin (TCPP) and Ag NPs loaded on MDTM@P−Ag can be activated to generate cytotoxic reactive oxygen species (ROS) and achieve photothermal conversion, thus effectively inducing the apoptosis of tumor cells and achieving a combined photodynamic/photothermal therapy. Once released at the tumor site, manganese dioxide (MnO₂) can catalyze the decomposition of hydrogen peroxide (H₂O₂) in the acidic microenvironment of the tumor to generate oxygen (O₂) and alleviate the hypoxic environment of the tumor. Fe³⁺/Mn²⁺ will mediate a Fenton/Fenton-like reaction to generate cytotoxic hydroxyl radicals (·OH), while depleting the high concentration of glutathione (GSH) in the tumor, thus enhancing the chemodynamic therapeutic effect. The successful preparation of the tumor drug delivery system and its good synergistic chemodynamic/photodynamic/photothermal therapeutic effect in tumor treatment can be demonstrated by the experimental results of material characterization, performance testing and in vitro experiments. Full article