Antioxidant and neuroprotective effects of dexpanthenol in rats induced with traumatic brain injury.

Trauma-induced primary damage is followed by secondary damage, exacerbating traumatic brain injury (TBI). Dexpanthenol has been shown to protect tissues against oxidative damage in various inflammation models. This study aimed to investigate possible antioxidant and neuroprotective effects of dexpanthenol in TBI. Wistar albino male rats were randomly assigned to control (n = 16), trauma (n = 16) and dexpanthenol (500 mg/kg; n = 14) groups. TBI was induced under anesthesia by dropping a 300 g weight from 70-cm height onto the skulls of the rats. Twenty-four hours after the trauma, the rats were decapitated and myeloperoxidase (MPO) levels, luminol- and lucigenin-enhanced chemiluminescence (CL), malondialdehyde (MDA) levels, superoxide dismutase (SOD) levels, and catalase (CAT) and caspase-3 activities were measured in brain tissues. Following transcardiac paraformaldehyde perfusion, histopathological damage was graded on hematoxylin-eosin-stained brain tissues. In the trauma group, MPO level, caspase-3 activity and luminol-lucigenin CL levels were elevated (p < 0.05-0.001) when compared to controls; meanwhile in the dexpanthenol group these increases were not seen (p < 0.05-0.001) and MDA levels were decreased (p < 0.05). Decreased SOD and CAT activities (p < 0.01) in the vehicle-treated TBI group were increased above control levels in the dexpanthenol group (p < 0.05-0.001). in the dexpanthenol group there was relatively less neuronal damage observed microscopically in the cortices after TBI. Dexpanthenol reduced oxidative damage, suppressed apoptosis by stimulating antioxidant systems and alleviated brain damage caused by TBI. Further experimental and clinical investigations are needed to confirm that dexpanthenol can be administered in the early stages of TBI.

Possible anti-inflammatory, antioxidant, and neuroprotective effects of apigenin in the setting of mild traumatic brain injury: an investigation.

OBJECTIVE: Apigenin is a plant flavone proven with biological properties such as anti-inflammatory, antioxidant, and antimicrobial effects. This study, it was aimed to examine the possible anti-inflammatory, antioxidant, and neuroprotective effects of apigenin in the setting of the mild traumatic brain injury (TBI) model. METHODS: Wistar albino male rats were randomly assigned to groups: control (n = 9), TBI (n = 9), TBI + vehicle (n = 8), and TBI + apigenin (20 and 40 mg/kg, immediately after trauma; n = 6 and n = 7). TBI was performed by dropping a 300 g weight from a height of 1 m onto the skull under anesthesia. Neurological examination and tail suspension tests were applied before and 24 h after trauma, as well as Y-maze and object recognition tests, after that rats were decapitated. In brain tissue, luminol- and lucigenin-enhanced chemiluminescence levels and cytokine ELISA levels were measured. Histological damage was scored. Data were analyzed with one-way ANOVA. RESULTS: After TBI, luminol (p < .001) and lucigenin (p < .001) levels increased, and luminol and lucigenin levels decreased with apigenin treatments (p < .01-.001). The tail suspension test score increased with trauma (p < .01). According to the pre-traumatic values, the number of entrances to the arms (p < .01) in the Y-maze decreased after trauma (p < .01). In the object recognition test, discrimination (p < .05) and recognition indexes (p < .05) decreased with trauma. There was no significant difference among trauma apigenin groups in behavioral tests. Interleukin (IL)-10 levels, one of the anti-inflammatory cytokines, decreased with trauma (p < .05), and increased with 20 and 40 mg apigenin treatment (p < .001 and p < .01, respectively). The histological damage score in the cortex was decreased in the apigenin 20 mg treatment group significantly (p < .05), but the decrease observed in the apigenin 40 mg group was not significant. CONCLUSION: The results of this study revealed that apigenin 20 and 40 mg treatment may have neuroprotective effects in mild TBI via decreasing the level of luminol and lucigenin and increasing the IL-10 levels. Additionally, apigenin 20 mg treatment ameliorated the trauma-induced cortical tissue damage.

Investigation of hydrodynamic cavitation induced reactive oxygen species production in microchannels via chemiluminescent luminol oxidation reactions.

Hydrodynamic cavitation was evaluated for its reactive oxygen species production in several convergent-divergent microchannel at the transition from micro to milli scale. Channel widths and heights were systematically varied to study the influence of geometrical parameters at the transitory scale. A photomultiplier tube was used for time-resolved photon detection and monitoring of the chemiluminescent luminol oxidation reactions, allowing for a contactless and in situ quantization of reactive oxygen species production in the channels. The radical production rates at various flow parameters were evaluated, showing an optimal yield per flow rate exists in the observed geometrical range. While cavitation cloud shedding was the prevailing regime in this type of channels, the photon arrival time analysis allowed for an investigation of the cavitation structure dynamics and their contribution to the chemical yield, revealing that radical production is not linked to the synchronous cavitation cloud collapse events. Instead, individual bubble collapses occurring throughout the cloud formation were recognized to be the source of the reactive oxygen species.

Self-Illuminated, Oxygen-Supplemented Photodynamic Therapy via a Multienzyme-Mimicking Nanoconjugate.

Current photodynamic therapy (PDT) faces several intrinsic limitations, including insufficient oxygen supply and limited penetration of external light sources. Herein, we report a nanoconjugate, which, in response to the elevated hydrogen peroxide levels associated with tumor tissues, can supplement the oxygen needed for PDT and provide local self-illumination. Consisting of a MnFe2O4 core, a metal-organic framework shell loaded with the chemiluminescence reagent luminol, and a hyaluronic acid surface coating, the nanoconjugate is highly effective for suppressing cancer tissues in vivo via PDT in the absence of externally delivered light.

Immune-Modulating Drug MP1032 with SARS-CoV-2 Antiviral Activity In Vitro: A potential Multi-Target Approach for Prevention and Early Intervention Treatment of COVID-19.

At least since March 2020, the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic and the multi-organ coronavirus disease 2019 (COVID-19) are keeping a firm grip on the world. Although most cases are mild, older patients and those with co-morbidities are at increased risk of developing a cytokine storm, characterized by a systemic inflammatory response leading to acute respiratory distress syndrome and organ failure. The present paper focuses on the small molecule MP1032, describes its mode of action, and gives rationale why it is a promising option for the prevention/treatment of the SARS-CoV-2-induced cytokine storm. MP1032 is a phase-pure anhydrous polymorph of 5-amino-2,3-dihydro-1,4-phthalazinedione sodium salt that exhibits good stability and bioavailability. The physiological action of MP1032 is based on a multi-target mechanism including localized, self-limiting reactive oxygen species (ROS) scavenging activities that were demonstrated in a model of lipopolysaccharide (LPS)-induced joint inflammation. Furthermore, its immune-regulatory and PARP-1-modulating properties, coupled with antiviral effects against SARS-CoV-2, have been demonstrated in various cell models. Preclinical efficacy was elucidated in LPS-induced endotoxemia, a model with heightened innate immune responses that shares many similarities to COVID-19. So far, during oral clinical development with three-month daily administrations, no serious adverse drug reactions occurred, highlighting the outstanding safety profile of MP1032.

Bioluminescence Imaging of Inflammation in Vivo Based on Bioluminescence and Fluorescence Resonance Energy Transfer Using Nanobubble Ultrasound Contrast Agent.

Inflammation is an immunological response involved in various inflammatory disorders ranging from neurodegenerative diseases to cancers. Luminol has been reported to detect myeloperoxidase (MPO) activity in an inflamed area through a light-emitting reaction. However, this method is limited by low tissue penetration and poor spatial resolution. Here, we fabricated a nanobubble (NB) doped with two tandem lipophilic dyes, red-shifting luminol-emitted blue light to near-infrared region through a process integrating bioluminescence resonance energy transfer (BRET) and fluorescence resonance energy transfer (FRET). This BRET-FRET process caused a 24-fold increase in detectable luminescence emission over luminol alone in an inflammation model induced by lipopolysaccharide. In addition, the echogenicity of the BRET-FRET NBs also enables perfused tissue microvasculature to be delineated by contrast-enhanced ultrasound imaging with high spatial resolution. Compared with commercially available ultrasound contrast agent, the BRET-FRET NBs exhibited comparable contrast-enhancing capability but much smaller size and higher concentration. This bioluminescence/ultrasound dual-modal contrast agent was then successfully applied for imaging of an animal model of breast cancer. Furthermore, biosafety experiments revealed that multi-injection of luminol and NBs did not induce any observable abnormality. By integrating the advantages of bioluminescence imaging and ultrasound imaging, this BRET-FRET system may have the potential to address a critical need of inflammation imaging.

Electrochemiluminescence for Electric-Driven Antibacterial Therapeutics.

The employment of physical light sources in clinical photodynamic therapy (PDT) system endows it with a crucial defect in the treatment of deeper tissue lesions due to the limited penetration depth of light in biological tissues. In this work, we constructed for the first time an electric driven luminous system based on electrochemiluminescence (ECL) for killing pathogenic bacteria, where ECL is used for the excitation of photosensitizer instead of a physical light source to produce reactive oxygen species (ROS). We named this new strategy as ECL-therapeutics. The mechanism for the ECL-therapeutics is dependent on the perfect spectral overlap and energy transfer from the ECL generated by luminol to photosensitizer, cationic oligo(p-phenylenevinylene) (OPV), to sensitize the surrounding oxygen molecule into ROS. Furthermore, taking into account the practical application of our ECL-therapeutics, we used flexible hydrogel to replace the liquid system to develop hydrogel antibacterial device. Because the chemical reaction is a slow process in the hydrogel, the luminescence could last for more than 10 min after only electrifying for five seconds. This unique persistent luminescence characteristic with long afterglow life makes them suitable for persistent antibacterial applications. Thus, stretchable and persistent hydrogel devices are designed by integrating stretchable hydrogel, persistent ECL and antibacterial function into hydrogel matrices. This novel strategy avoids the employment of external light source, making it simple, convenient and controllable, which exploits a new field for ECL beyond sensors and also opens up a new model for PDT.

[Action of Combined Magnetic Fields with a Very Weak Low-frequency Alternating Component on Luminol-dependent Chemiluminescence in Mammalian Blood].

It is shown that the exposure of heparinized venous human blood diluted in phosphate buffer saline to extremely weak alternating magnetic fields of the ultralow-frequency (1 Hz, 600 nT; 4.4 Hz, 100 nT; 16.5 Hz, 160 nT) in combination with a collinear static magnetic field of 42 microT at physiological temperatures, causes a sharp 3-4 fold increase in its chemiluminescence after addition of luminol.

[Peripheral blood cells luminol-dependent chemiluminescence at the different stages of atopic dermatitis].

UNLABELLED: Aim of this work was to record the luminol-dependent spontaneous and induced chemiluminescence at the different stages of atopic dermatitis. METHODS: Peripheral blood cells were obtained from adult patient with atopic dermatitis followed by the registration of luminol-dependent chemiluminescence on luminograph. Opsonized zymosan as well as yeasts Candida tropicalis have been used to induce the chemiluminescence. RESULTS: Spontaneous and induced chemiluminescence were slightly elevated at the mild atopic dermatitis but were decreased at the severe stage of disease. Statistically significant difference has been found between group with mild and severe atopic dermatitis, Skin contamination by yeasts Candida tropicalis causes the increased level of blood cells chemiluminescence at the first week of atopic relapse when the disease was mild. Severe stage of atopic dermatitis was coupled with statistically significant inhibition of both, spontaneous and induced chemiluminescence. CONCLUSIONS: Luminol-dependent chemiluminescence of peripheral blood cells from adult atopic dermatitis patients may be stimulated at the mild stage and suppressed at severe stage of atopic dermatitis.

[The role of cellular mediators in the development of the phenomenon of inhibition induced by barium sulfate luminol-dependent chemiluminescence of blood under the influence of non-steroidal anti-inflammatory drugs in patients with intolerance to these drugs].

We investigated contribution mediator mechanism in the development of the phenomenon of inhibition induced by barium sulfate luminol-dependent chemiluminescence (SLCHL) of blood under the influence of nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with intolerance to these drugs. It was found that the phenomenon of suppression SLCHL blood under the influence of NSAIDs in patients with intolerance is mediated by the participation of mediators, and the contribution of H1--and H2--histamine receptors, 5-HT2 serotonin receptors and Cys-leukotriene receptors in the development of that phenomenon depends on the chemical nature of NSAIDs and the clinical manifestations of intolerance.

Modulation of macrophages and response of CD117(+) cells of different localization after liver damage in mice.

We studied the effects of stimulation of mononuclear phagocyte system on the state of CD117(+) hepatocytes of growth zone and CD117(+) hemopoietic stem cells after liver damage. Increased number of CD117(+) hepatocytes and enhanced expression of given antigen was revealed. CD117(+) hemopoietic stem cells respond to the impact by migration to the regenerating organ.

[The chemiluminescent detection of activity in peripheral blood neutrophils under allergic diseases of lungs in children with fungous sensibilization].

The high mobilization activity of neutrophils as a capacity of momentary feed-back reaction to factually any external stimuli, make it possible to use them in various diagnostic systems in vitro. Among them is the automated test system of chemiluminescent detection of functional activity of peripheral blood neutrophils in parallel response to luminol, opsonizing zymosan and different antigens. This approach makes it possible to evaluate the initial and induced activity of phagocytes and its dynamics in case of adding in vitro to test system of one or another allergen. The application of micro technique of chemiluminescent detection of functional activity of peripheral blood neutrophils revealed the stimulating effect of allergens Aaspergillus fumigatus, Alternaria alternata, Cladosporum herbatum, Candida albicans and Penicillinum notatum. This is an additional evidence of high sensitivity of children with allergic diseases of lungs to fungi and hence one more factor of diagnostics and treatment.

[Effect of opioid peptides on oxygen-dependent microbicidity of peripheral blood neutrophils].

Investigation ofopioid peptide effect on the production of reactive oxygen species by neutrophils in non-fractionated leukocyte suspension and in purified fraction of peripheral blood neutrophils is disclosed in this work. It was determined that selective delta- and micro-agonists of peptide origin stimulated the spontaneous and suppressed 15 mkg/ml zymosan-induced LDCL (luminol-dependent chemiluminescence) reaction of neutrophils in leukocyte suspension. beta-endorphin was found to render less marked suppressive action on 15 mkg/ml zymosan-induced LDCL, and delta2-agonist deltorphin 2 promoted 15 mkg/ml zymosan-induced LDCL only toward the 25 minutes of the experiment. beta-endorphin and selective d- and m- agonists did not affect the spontaneous and suppressed 15 mkg/ml and 150 mkg/ml zymosan-induced neutrophil LDCL. Therefore, opioid peptides play essential role in the process of direct and indirect regulation of oxygen-dependent system of neutrophil granulocyte bactericidal activity.

Reaction of CD117+ cells to renal lesion under conditions of phagocytic mononuclear system stimulation.

The content of CD117(+)cells in the kidneys and CD45(low)CD117(+)cells in the bone marrow and blood of mice were studied after partial nephrectomy and under conditions of macrophage stimulation with 3-aminophthalhydrazide. The counts of tubular CD117(+)epitheliocytes sharply increased and the content of CD45(low)CD117(+)cells in the bone marrow decreased after renal damage. Injection of 3-aminophthalhydrazide stimulated the expression of CD117 by renal epitheliocytes and led to reduction of CD45(low)CD117(+)cell counts in the bone marrow and blood. Macrophages stimulated proliferative processes in the kidney and differentiation of stem cells in the bone marrow due to synergic effects of their cytokines and stem cell factor.

Metabolic impact of 4-hydroxynonenal on macrophage-like RAW 264.7 function and activation.

Metabolic profiling of macrophage metabolic response upon exposure to 4-hydroxynonenal (HNE) demonstrates that HNE does not simply inactivate superoxide-generating enzymes but also could be responsible for the impairment of downfield signaling pathways. Multianalyte microphysiometry (MAMP) was employed to simultaneously measure perturbations in extracellular acidification, lactate production, and oxygen consumption for the examination of aerobic and anaerobic pathways. Combining the activation of oxidative burst with phorbol myristate acetate (PMA) and the immunosuppression with HNE, the complex nature of HNE toxicity was determined to be concentration- and time-dependent. Further analysis was utilized to assess the temporal effect of HNE on reactive oxygen species (ROS) production and on protein kinase C (PKC). Increased levels of HNE with decreasing PKC activity suggest that PKC is a target for HNE adductation prior to oxidative burst. Additionally, localization of PKC to the cell membrane was prevented with the introduction of HNE, demonstrating a consequence of HNE adductation on NADPH activation. The impairment of ROS by HNE suggests that HNE has a greater role in foam cell formation and tissue damage than is already known. Although work has been performed to understand the effect of HNE's regulation of specific signaling pathways, details regarding its involvement in cellular metabolism as a whole are generally unknown. This study examines the impact of HNE on macrophage oxidative burst and identifies PKC as a key protein for HNE suppression and eventual metabolic response.

Modulation of reparative regeneration and CD117 expression by liver cells after partial hepatectomy in mice.

The effects of 3-aminophthalhydrazide and carrageenan on reparative regeneration and expression of CD117 by liver cells after partial hepatectomy were studied in mice. 3-Aminophthalhydrazide stimulated regeneration of the liver and increased the count of CD117(+) hepatocytes. By contrast, carrageenan inhibited liver reparation and CD117 expression.

WT-1 mRNA expression is modulated by nitric oxide availability and Hsp70 interaction after neonatal unilateral ureteral obstruction

Wilms tumor gene 1 (wt-1), a key regulator of mesenchymal-epithelial transformation, is downregulated during congenital obstructive nephropathy, leading to apoptosis. There is a functional interaction between WT-1 and inducible nitric oxide synthase (iNOS). In this regard, we reported that after neonatal unilateral ureteral obstruction, rosuvastatin prevents apoptosis through an increase in nitric oxide bioavailability, which in turn is linked to higher Hsp70 expression. Hence, the goal of this study was to determine whether a nitric oxide/Hsp70 interaction is involved in changes in WT-1 mRNA expression after ureteral obstruction. Neonatal rats submitted to experimental ureteral obstruction were treated with either vehicle or rosuvastatin for 14 days. Decreased nitric oxide and iNOS/Hsp70 expression associated wit h WT-1 low expression was shown in obstructed kidneys. Apoptosis was induced and it was associated with an increased Bax/BcL2 ratio. Conversely, iNOS/Hsp70 upregulation and an increased WT-1 mRNA expression, without an apoptotic response, were observed in the cortex of obstructed kidneys of rosuvastatin-treated rats. Nitric oxide also modulated Hsp70 and WT-1 mRNA expression in MDCK cells. Finally, in vivo experiments with nitric oxide modulators support our hypothesis that WT-1 mRNA expression is associated with nitric oxide level. Results suggest that rosuvastatin may modulate WT-1 mRNA expression through renal nitric oxide bioavailability, preventing neonatal obstruction-induced apoptosis associated with Hsp70 interaction.

WT-1 mRNA expression is modulated by nitric oxide availability and Hsp70 interaction after neonatal unilateral ureteral obstruction

Wilms tumor gene 1 (wt-1), a key regulator of mesenchymal-epithelial transformation, is downregulated during congenital obstructive nephropathy, leading to apoptosis. There is a functional interaction between WT-1 and inducible nitric oxide synthase (iNOS). In this regard, we reported that after neonatal unilateral ureteral obstruction, rosuvastatin prevents apoptosis through an increase in nitric oxide bioavailability, which in turn is linked to higher Hsp70 expression. Hence, the goal of this study was to determine whether a nitric oxide/Hsp70 interaction is involved in changes in WT-1 mRNA expression after ureteral obstruction. Neonatal rats submitted to experimental ureteral obstruction were treated with either vehicle or rosuvastatin for 14 days. Decreased nitric oxide and iNOS/Hsp70 expression associated wit h WT-1 low expression was shown in obstructed kidneys. Apoptosis was induced and it was associated with an increased Bax/BcL2 ratio. Conversely, iNOS/Hsp70 upregulation and an increased WT-1 mRNA expression, without an apoptotic response, were observed in the cortex of obstructed kidneys of rosuvastatin-treated rats. Nitric oxide also modulated Hsp70 and WT-1 mRNA expression in MDCK cells. Finally, in vivo experiments with nitric oxide modulators support our hypothesis that WT-1 mRNA expression is associated with nitric oxide level. Results suggest that rosuvastatin may modulate WT-1 mRNA expression through renal nitric oxide bioavailability, preventing neonatal obstruction-induced apoptosis associated with Hsp70 interaction.(AU)

Chemiluminescence assay of reactive oxygen species in laryngeal cancer.

OBJECTIVE: This study aimed to evaluate the presence of reactive oxygen species in laryngeal cancer tissue, using a luminol-amplified chemiluminescence method. MATERIALS AND METHODS: Fourteen patients with histopathologically diagnosed laryngeal squamous cell carcinoma were enrolled. Patients with recurrent tumours or a history of prior chemotherapy or radiotherapy were excluded. Tissue specimens were harvested both from the tumour itself and from the neighbouring, apparently normal mucosa (immediately after tumour removal). Tissue specimens were washed with ice-cold saline solution and processed immediately, without storage. The level of reactive oxygen species was measured quantitatively by a luminol-amplified chemiluminescence method. RESULTS: The mean luminol-amplified chemiluminescence values for tumour and control tissue were 140.52 (standard error of the mean 40.21) and 121.36 (standard error of the mean 35.33) relative light units/mg tissue, respectively. Furthermore, mean tumour and control luminol chemiluminescence values were compared for stage one and two tumours versus stage three and four tumours. Both the tumour and the control luminol chemiluminescence values for the latter tumour group were significantly higher than those for the former tumour group. CONCLUSION: This study measured directly the levels of reactive oxygen species in samples of laryngeal cancer tissue and normal mucosa. Higher levels of reactive oxygen species were found in laryngeal cancer tissue, suggesting a relationship between reactive oxygen species and laryngeal cancer.

Neuroprotective effects of the drug GVT (monosodium luminol) are mediated by the stabilization of Nrf2 in astrocytes.

Oxidative stress is implicated in various kinds of neurological disorders, including human immunodeficiency virus (HIV) associated dementia (HAD). Our laboratory has been studying the murine retrovirus ts1, a pathogenic mutant of the Moloney murine leukemia virus (MoMuLV), as a model for HAD. Like HIV in humans, ts1 induces oxidative stress and progressive neurodegeneration in mice. We have shown previously that an antioxidant and anti-inflammatory drug GVT or MSL (monosodium luminol) suppresses ts1-induced oxidative stress, attenuates the development of spongiform encephalopathy, and delays hind limb paralysis in infected mice. It is known that upregulation of the nuclear transcription factor NF-E2-related factor 2 (Nrf2) is involved in upregulating cellular antioxidant defenses. Since Nrf2 is associated with elevation of antioxidant defenses in general, and since GVT suppresses ts1-induced neurodegeneration, our aim in this study was to determine whether GVT neuroprotection is linked to Nrf2 upregulation in the brain. We report here that GVT upregulates the levels of Nrf2, both in primary astrocyte cultures and in brainstem of ts1-infected mice. Significant upregulation of Nrf2 expression by GVT occurs in both the cytosolic and nuclear fractions of cultured astrocytes and brainstem cells. Notably, although GVT treatment increases Nrf2 protein levels in cultured astrocytes and brainstem tissues, Nrf2 mRNA levels are not altered. This suggests that the neuroprotective effects of GVT may be mediated by the stabilization of the Nrf2 protein, allowing continuous upregulation of Nrf2 levels in the astrocytes.