Search

Hydrogen sulfide (H2S) is particularly produced in the skin, where it participates in the regulation of inflammation, pruritus, cytoprotection, scarring, and angiogenesis. In this study, we compared the effects of dexamethasone (Dex) with two H2S-releasing Dex derivatives in a murine model of atopic dermatitis (AD) induced by topical application of 2,4-dinitrochlorobenzene (DNCB). After sensitization with DNCB, the animals were topically treated for five consecutive days with either the H2S-releasing compounds 4-hydroxy-thiobenzamide (TBZ) and 5-(p-hydroxyphenyl)-1,2-dithione-3-thione (ADT-OH), Dex, or the derivatives Dex-TBZ or Dex-ADT. Topical treatment with equimolar doses of either Dex, Dex-TBZ, or Dex-ADT resulted in similar reductions in dermatitis score, scratching behavior, edema, eosinophilia, splenomegaly, and histological changes. In contrast with Dex, the H2S-releasing derivatives prevented IL-4 elevation and oxidative modification of skin proteins. On an equimolar dose basis, Dex-TBZ, but not Dex-ADT, promoted the elevation of endogenous H2S production and GPx activity. Neither Dex-TBZ nor Dex-ADT decreased GR activity or caused hyperglycemia, as observed with Dex treatment. We conclude that the presence of H2S-releasing moieties in the Dex structure does not interfere with the anti-inflammatory effects of this corticosteroid and adds beneficial therapeutical actions to the parent compound. [ABSTRACT FROM AUTHOR]

Mentha piperita L. (peppermint) possesses antimicrobial properties, but little is known of its ability to modulate macrophages. Macrophages are essential in bacterial infection control due to their antimicrobial functions and ability to link the innate and adaptive immune responses. We evaluated the effects of the peppermint leaf hydroalcoholic extract (LHAE) on cultured murine peritoneal macrophages stimulated or not with lipopolysaccharide (LPS) in vitro. Vehicle-treated cells were used as controls. The constituents of the extract were also identified. Epicatechin was the major compound detected in the LHAE. LPS-induced macrophage death was reversed by incubation with LHAE (1-30 μg/ml). Higher concentrations of the extract (≥100 μg/ml) decreased macrophage viability (49-57%) in the absence of LPS. LHAE (1-300 μg/ml) attenuated H2O2 (34.6-53.4%) but not nitric oxide production by these cells. At similar concentrations, the extract increased the activity of superoxide dismutase (15.3-63.5-fold) and glutathione peroxidase (34.4-73.6-fold) in LPS-treated macrophages. Only LPS-unstimulated macrophages presented enhanced phagocytosis (3.6-6.6-fold increase) when incubated with LHAE (3-30 μg/ml). Overall, the LHAE obtained from peppermint modulates macrophage-mediated inflammatory responses, by stimulating the antioxidant pathway in these cells. These effects may be beneficial when the excessive activation of macrophages contributes to tissue damage during infectious disease. [ABSTRACT FROM AUTHOR]

This study aimed to compare the anti-neoplastic effects of an Uncaria tomentosa (UT) brute hydroethanolic (BHE) extract with those of two fractions derived from it. These fractions are choroformic (CHCl3) and n-butanolic (BuOH), rich in pentacyclic oxindole alkaloids (POA) and antioxidant substances, respectively. The cancer model was the subcutaneous inoculation of Walker-256 tumour cells in the pelvic limb of male Wistar rat. Subsequently to the inoculation, gavage with BHE extract (50 mg.kg−1) or its fractions (as per the yield of the fractioning process) or vehicle (Control) was performed during 14 days. Baseline values, corresponding to individuals without tumour or treatment with UT, were also included. After treatment, tumour volume and mass, plasma biochemistry, oxidative stress in liver and tumour, TNF-α level in liver and tumour homogenates, and survival rates were analysed. Both the BHE extract and its BuOH fraction successfully reduced tumour weight and volume, and modulated anti-oxidant systems. The hepatic TNF-α level indicated a greater effect from the BHE extract as compared to its BuOH fraction. Importantly, both the BHE extract and its BuOH fraction increased the survival time of the tumour-bearing animals. Inversely, the CHCl3 fraction was ineffective. These data represent an in vivo demonstration of the importance of the modulation of oxidative stress as part of the anti-neoplastic activity of UT, as well as constitute evidence of the lack of activity of isolated POAs in the primary tumour of this tumour lineage. These effects are possibly resulting from a synergic combination of substances, most of them with antioxidant properties. [ABSTRACT FROM AUTHOR]

Introduction: The human umbilical artery (HUA), rat-isolated right atrium, and rat-isolated vas deferens present a basal release of 6-nitrodopamine (6-ND). The basal release of 6-ND from these tissues was significantly decreased (but not abolished) when the tissues were pre-incubated with N ω -nitro-L-arginine methyl ester (L-NAME). Methods: In this study, the effect of the pharmacological modulation of the redox environment on the basal release of 6-ND was investigated. The basal release of 6-ND was measured using Liquid chromatography with tandem mass spectrometry (LC-MS/MS). Results and Discussion: Pre-incubation (30 min) of the tissues with GKT137831 (1 μM) caused a significant increase in the basal release of 6-ND from all tissues. In the HUA, pre-incubation with diphenyleneiodonium (DPI) (100 μM) also caused significant increases in the basal release of 6-ND. Preincubation of the HUA with hydrogen peroxide (H 2 O 2 ) (100 μM) increased 6-ND basal release, whereas pre-incubation with catalase (1,000 U/mL) significantly decreased it. Pre-incubation of the HUA with superoxide dismutase (SOD) (250 U/mL; 30 min) also significantly increased the basal release of 6-ND. Preincubation of the HUA with either allopurinol (100 μM) or uric acid (1 mM) had no effect on the basal release of 6-ND. Pre-treatment of the HUA with L-NAME (100 μM) prevented the increase in the basal release of 6-ND induced by GKT137831, diphenyleneiodonium, and H 2 O 2 . The results obtained indicate a major role of endogenous H2O2 and peroxidases as modulators of 6- ND biosynthesis/release and a lack of peroxynitrite contribution., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Britto-Júnior, Furlaneto, Lima, de Oliveira, Severino, Frecentese, Fiorino, Caliendo, Muscará and De Nucci.)

Introduction: Hydrogen sulfide (H 2 S) is a fundamental biological endogenous gas-mediator in the respiratory system. It regulates pivotal patho-physiological processes such as oxidative stress, pulmonary circulation, airway tone and inflammation., Objectives: We herein describe the design and synthesis of molecular hybrids obtained by the condensation of several corticosteroids with different hydrogen sulfide releasing moieties., Methods: All the molecules are characterized for their ability to release H 2 S both via amperometric approach and using a fluorescent probe. The chemical stability of the newly synthesized hybrid molecules has been investigated at differing pH values and in human serum., Results: Prednisone-TBZ hybrid (compound 7 ) was selected for further evaluations. The obtained results from the in vitro and in vivo studies clearly show evidence in favor of the anti-inflammatory properties of the released H 2 S., Conclusions: The protective effect on airway remodeling makes the hybrid Prednisone-TBZ (compound 7 ) as a promising therapeutic option in reducing allergic asthma symptoms and exacerbations., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors. Published by Elsevier B.V. on behalf of Cairo University.)

Mentha piperita L. (peppermint) possesses antimicrobial properties, but little is known of its ability to modulate macrophages. Macrophages are essential in bacterial infection control due to their antimicrobial functions and ability to link the innate and adaptive immune responses. We evaluated the effects of the peppermint leaf hydroalcoholic extract (LHAE) on cultured murine peritoneal macrophages stimulated or not with lipopolysaccharide (LPS) in vitro . Vehicle-treated cells were used as controls. The constituents of the extract were also identified. Epicatechin was the major compound detected in the LHAE. LPS-induced macrophage death was reversed by incubation with LHAE (1-30  μ g/ml). Higher concentrations of the extract (≥100  μ g/ml) decreased macrophage viability (49-57%) in the absence of LPS. LHAE (1-300  μ g/ml) attenuated H 2 O 2 (34.6-53.4%) but not nitric oxide production by these cells. At similar concentrations, the extract increased the activity of superoxide dismutase (15.3-63.5-fold) and glutathione peroxidase (34.4-73.6-fold) in LPS-treated macrophages. Only LPS-unstimulated macrophages presented enhanced phagocytosis (3.6-6.6-fold increase) when incubated with LHAE (3-30  μ g/ml). Overall, the LHAE obtained from peppermint modulates macrophage-mediated inflammatory responses, by stimulating the antioxidant pathway in these cells. These effects may be beneficial when the excessive activation of macrophages contributes to tissue damage during infectious disease.

Oxidative stress has been implicated in motoneuron death secondary to axotomy in the neonatal period. We studied the effect of sciatic transection at P2 on the motoneuron population in the lumbar enlargement of newborn rats looking for a protective role of daily doses of the antioxidant melatonin. The animals were allowed to survive from P2 to P7, and the spinal cords were processed for immunohistochemistry for superoxide dismutase (SOD) isoforms 1 and 2 and nitric oxide synthase (nNOS) (at 2, 3, 5, and 7 days post-natum), histological neuron counting and immunoblotting for the SOD isoforms (both at 2, 3, and 7 days post-natum). Melatonin reduced by 75% motoneuron loss due to axotomy at P3 and P7. Neither sciatic transection nor melatonin induced any detectable changes in the immunoreactivity patterns of the enzymes. SOD1 was expressed diffusely in the cytoplasm of neurons and ependyma and in the nuclei of presumed glial cells from P2 to P7. SOD2 was detected in neurons and ependyma and its expression was similar to SOD1 at P2 but decreased later to a spotty cytoplasmic pattern in motoneurons. nNOS was localized to the cytoplasm of a few small cells in the ventral and dorsal horns and around the central canal. Immunoblotting at 1 day postaxotomy detected a significant increase in SOD1 expression in melatonin-treated axotomized rats and a decrease in controls after axotomy and vehicle. Blotting for SOD2 did not show significant changes between groups at any time. This study provides the first evidence that SOD2 immunostaining pattern varies during motoneuron postnatal development and that melatonin alters the expression of SOD1 in the present model of peripheral nerve injury.