Repercussions of Long-Term Naproxen Administration on LPS-Induced Periodontitis in Male Mice.

Aims: Chronic periodontitis is the sixth most prevalent disease worldwide and the leading cause of tooth loss in adults. With growing attention on the role of inflammatory and immune responses in its pathogenesis, there is an urgent need to evaluate host-modulatory agents. Non-steroidal anti-inflammatory drugs (NSAIDs) drugs play a crucial role in managing inflammatory conditions.

Development and evaluation of nanostructured systems for cutaneous delivery of HS-releasing corticosteroids for skin inflammatory diseases.

Psoriasis is an immune-mediated chronic inflammatory disease that causes major psychosocial impact. Topical corticosteroids represent the standard pharmacological treatment for mild-to-moderate disease, but their local and systemic adverse effects reinforce the need for treatment innovations. Here we developed lamellar phase-based formulations for topical delivery of a hybrid dexamethasone and hydrogen sulfide (HS) donor molecule (Dexa-TBZ), aiming to potentiate the effects of the glucocorticoid with HS.

GKT137831 and hydrogen peroxide increase the release of 6-nitrodopamine from the human umbilical artery, rat-isolated right atrium, and rat-isolated vas deferens.

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-nitro-L-arginine methyl ester (L-NAME). In this study, the effect of the pharmacological modulation of the redox environment on the basal release of 6-ND was investigated.

Disruption of Atrial Rhythmicity by the Air Pollutant 1,2-Naphthoquinone: Role of Beta-Adrenergic and Sensory Receptors.

The combustion of fossil fuels contributes to air pollution (AP), which was linked to about 8.79 million global deaths in 2018, mainly due to respiratory and cardiovascular-related effects. Among these, particulate air pollution (PM2.

Hydrogen Sulfide Signaling in the Tumor Microenvironment: Implications in Cancer Progression and Therapy.

Cancer is a complex and heterotypic structure with a spatial organization that contributes to challenges in therapeutics. Enzymes associated with producing the gasotransmitter hydrogen sulfide (HS) are differentially expressed in tumors. Indeed, critical and paradoxical roles have been attributed to HS in cancer-promoting characteristics by targeting both cancer cells and their milieu.

Beneficial Effects of Two Hydrogen Sulfide (HS)-Releasing Derivatives of Dexamethasone with Antioxidant Activity on Atopic Dermatitis in Mice.

Hydrogen sulfide (HS) 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 HS-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 HS-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.

Periprostatic adipose tissue (PPAT) supernatant from obese mice releases anticontractile substances and increases human prostate epithelial cell proliferation: the role of nitric oxide and adenosine.

The prostate gland is surrounded by periprostatic adipose tissue (PPAT) that can release mediators that interfere in prostate function. In this study, we examined the effect of periprostatic adipose tissue supernatant obtained from obese mice on prostate reactivity and on the viability of human prostatic epithelial cell lines. Male C57BL/6 mice were fed a standard or high-fat diet after which PPAT was isolated, incubated in Krebs-Henseleit solution for 30 min (without prostate) or 60 min (with prostate), and the supernatant was then collected and screened for biological activity.

The effect of MK-801 on stress-ethanol cross-sensitization is dissociable from its effects on nNOS activity.

Locomotor behavioral sensitization represents an animal model for understanding neuroadaptive processes related to repeated drug exposure. Repeated stress can elicit a cross-sensitization to the stimulant response of ethanol, which involves neuronal nitric oxide synthase (nNOS). Activation of N-methyl d-aspartate (NMDA) glutamate receptors triggers nNOS and the synthesis of nitric oxide (NO).

salivary gland extract alleviates acute itching by blocking TRPA1 channels.

() saliva induces a variety of anti-inflammatory and immunomodulatory activities. Interestingly, although it is known that mosquito bites cause allergic reactions in sensitised hosts, the primary exposure of humans to does not evoke significant itching. Whether active components in the saliva of can counteract the normal itch reaction to injury produced by a histaminergic or non-histaminergic pathway in vertebrate hosts is unknown.

Role of Gasotransmitters in Inflammatory Edema.

Nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (HS) are, to date, the identified members of the gasotransmitter family, which consists of gaseous signaling molecules that play central roles in the regulation of a wide variety of physiological and pathophysiological processes, including inflammatory edema. Recent studies show the potential anti-inflammatory and antiedematogenic effects of NO-, CO-, and HS-donors . In general, it has been observed that the therapeutical effects of NO-donors are more relevant when administered at low doses at the onset of the inflammatory process.

An Overview of the TRP-Oxidative Stress Axis in Metabolic Syndrome: Insights for Novel Therapeutic Approaches.

Metabolic syndrome (MS) is a complex pathology characterized by visceral adiposity, insulin resistance, arterial hypertension, and dyslipidaemia. It has become a global epidemic associated with increased consumption of high-calorie, low-fibre food and sedentary habits. Some of its underlying mechanisms have been identified, with hypoadiponectinemia, inflammation and oxidative stress as important factors for MS establishment and progression.

Vasorelaxant Activity of AP39, a Mitochondria-Targeted HS Donor, on Mouse Mesenteric Artery Rings In Vitro.

Mitochondria-targeted hydrogen sulfide (HS) donor compounds, such as compound AP39, supply HS into the mitochondrial environment and have shown several beneficial in vitro and in vivo effects in cardiovascular conditions such as diabetes and hypertension. However, the study of their direct vascular effects has not been addressed to date. Thus, the objective of the present study was to analyze the effects and describe the mechanisms of action of AP39 on the in vitro vascular reactivity of mouse mesenteric artery.

Metformin disrupts insulin secretion, causes proapoptotic and oxidative effects in rat pancreatic beta-cells in vitro.

Metformin is the first-line drug to treat type 2 diabetes mellitus. Its mechanism of action is still debatable, and recent studies report that metformin attenuates oxidative stress. This study evaluated the in vitro antioxidant effects of a broad range of metformin concentrations on insulin-producing cells.

HS donating corticosteroids: Design, synthesis and biological evaluation in a murine model of asthma.

Introduction: Hydrogen sulfide (HS) 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.

Leukotriene receptor antagonist reduces inflammation and alveolar bone loss in a rat model of experimental periodontitis.

Background: Leukotrienes (LTs) participate in the process of tissue damage in periodontal disease by leukocyte chemotaxis and osteoclastic activation. The activation of Cysteinyl-LT receptor is associated with increased expression of proinflammatory molecules and osteoclastogenesis. However, its implications on periodontal disease progression have not been studied.

The potential anti-inflammatory and anti-nociceptive effects of rat hemopressin (PVNFKFLSH) in experimental arthritis.

Inflammatory arthritis, such as rheumatoid arthritis (RA), stands out as one of the main sources of pain and impairment to the quality of life. The use of hemopressin (PVNFKFLSH; Hp), an inverse agonist of type 1 cannabinoid receptor, has proven to be effective in producing analgesia in pain models, but its effect on neuro-inflammatory aspects of RA is limited. In this study, antigen-induced arthritis (AIA) was evoked by the intraarticular (i.

Molecular mechanism and health effects of 1,2-Naphtoquinone.

Extensive literature regarding the health side effects of ambient pollutants (AP) are available, such as diesel exhaust particles (DEPs), but limited studies are available on their electrophilic contaminant 1,2-Naphthoquinone (1,2-NQ), enzymatically derived from naphthalene. This review summarizes relevant toxicologic and biological properties of 1,2-NQ as an environmental pollutant or to a lesser degree as a backbone in drug development to treat infectious diseases. It presents evidence of 1,2-NQ-mediated genotoxicity, neurogenic inflammation, and cytotoxicity due to several mechanistic properties, including the production of reactive oxygen species (ROS), that promote cell damage, carcinogenesis, and cell death.

Enhanced Analgesic Effects and Gastrointestinal Safety of a Novel, Hydrogen Sulfide-Releasing Anti-Inflammatory Drug (ATB-352): A Role for Endogenous Cannabinoids.

The covalent linking of nonsteroidal anti-inflammatory drugs to a hydrogen sulfide (HS)-releasing moiety has been shown to dramatically reduce gastrointestinal (GI) damage and bleeding, as well as increase anti-inflammatory and analgesic potency. We have tested the hypothesis that an HS-releasing derivative of ketoprofen (ATB-352) would exhibit enhanced efficacy without significant GI damage in a mouse model of allodynia/hyperalgesia. ATB-352 was significantly more potent and effective as an analgesic than ketoprofen and did not elicit GI damage.

l-Arginine supplementation blunts resistance exercise improvement in rats with chronic kidney disease.

Chronic kidney disease (CKD) patients present L-arginine (L-arg) deficiency and L-arg supplementation has been used as a treatment. In addition, sarcopenia is another common problem in CKD population, resistance training (RT) is one of the conservative strategies developed to prevent CKD progression, and however there are no evidences of a combination of these two strategies to treat CKD outcomes. The aim of this study was to evaluate the effects of oral L-arg supplementation combined with RT in an experimental model of CKD.

TRPV1 Contributes to Cerebral Malaria Severity and Mortality by Regulating Brain Inflammation.

Transient receptor potential vanilloid 1 (TRPV1) is a Ca-permeable channel expressed on neuronal and nonneuronal cells, known as an oxidative stress sensor. It plays a protective role in bacterial infection, and recent findings indicate that this receptor modulates monocyte populations in mice with malaria; however, its role in cerebral malaria progression and outcome is unclear. By using TRPV1 wild-type (WT) and knockout (KO) mice, the importance of TRPV1 to this cerebral syndrome was investigated.

Hydrogen sulfide inhibits apoptosis and protects the bronchial epithelium in an allergic inflammation mice model.

Studies suggest that hydrogen sulfide (HS) plays a relevant and beneficial role in the pathophysiology of pulmonary allergic diseases, such as asthma. These diseases may be triggered by changes in airway epithelium caused by repeated exposure to environmental allergens. This study aimed to investigate whether HS protects against bronchial epithelium apoptosis in allergic inflammation in mice.

Hydrogen sulfide and dermatological diseases.

Skin diseases constitute a major health problem affecting a high proportion of the population every day and have different aetiologies that include inflammation, infections, and tumours. Hydrogen sulfide (H S) is a gaseous signalling molecule recognized as a gasotransmitter together with NO and carbon monoxide. Under physiological conditions, H S is produced in the skin by enzymic pathways and plays a physiological role in a variety of functions, such as vasodilatation, cell proliferation, apoptosis, and inflammation.

Effects of Selective Versus Non-Selective COX-2 Inhibition on Experimental Periodontitis.

In the present study we compared the effects of the selective COX-2 inhibitor etoricoxib with those of the classical non-selective NSAID diclofenac on the inflammatory process and alveolar bone loss in an experimental model of periodontitis in rats. Ninety male Holtzman rats (250 g) were randomly sorted into four experimental groups: Sham+CMC and Ligature+CMC (control) groups which received 0.5% carboxymethylcellulose sodium (CMC) solution; Ligature+Diclofenac and Ligature+Etoricoxib groups which received Potassium Diclofenac and Etoricoxib, respectively, suspended in 0.

Hydrogen peroxide-based products alter inflammatory and tissue damage-related proteins in the gingival crevicular fluid of healthy volunteers: a randomized trial.

Hydrogen peroxide (HO)-based products are effective in tooth whitening; however, their safety is controversial as they may harm patient tissues/cells. These effects are suggested to be concentration-dependent; nonetheless, to date, there are no reports on HO-mediated oxidative damage in the gingival tissue, and neither whether this can be detected in gingival crevicular fluid (GCF) samples. We hypothesize that HO whitening products may cause collateral oxidative tissue damage following in office application.

A proof-of-concept, Phase 2 clinical trial of the gastrointestinal safety of a hydrogen sulfide-releasing anti-inflammatory drug.

Background And Purpose: ATB-346 is a hydrogen sulfide (H S)-releasing anti-inflammatory and analgesic drug. Animal studies demonstrated negligible gastrointestinal (GI) damage despite marked inhibition of COX activity and significant analgesic and anti-inflammatory effects. In humans, ATB-346 (250 mg once daily) was found to inhibit COX to the same extent as naproxen (550 mg twice daily).