scholarly journals The Inhibitory Effects of Slow-Releasing Hydrogen Sulfide Donors in the Mechanical Allodynia, Grip Strength Deficits, and Depressive-Like Behaviors Associated with Chronic Osteoarthritis Pain

Antioxidants ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 31 ◽  
Author(s):  
Gerard Batallé ◽  
Laura Cabarga ◽  
Olga Pol
Keyword(s):  
Hydrogen Sulfide ◽  
Grip Strength ◽  
Emotional Disorders ◽  
Mechanical Allodynia ◽  
Functional Disability ◽  
Negative Impact ◽  
Allyl Isothiocyanate ◽  
Phenyl Isothiocyanate ◽  
Heme Oxygenase 1 ◽  
Osteoarthritis Pain

Osteoarthritis and its associated comorbidities are important clinical problems that have a negative impact on the quality of life, and its treatment remains unresolved. We investigated whether the systemic administration of slow-releasing hydrogen sulfide (H2S) donors, allyl isothiocyanate (A-ITC) and phenyl isothiocyanate (P-ITC), alleviates chronic osteoarthritis pain and the associated emotional disorders. In C57BL/6 female mice with osteoarthritis pain induced by the intra-articular injection of monosodium iodoacetate, we evaluated the effects of repeated administration of A-ITC and P-ITC on the (i) mechanical allodynia and grip strength deficits; (ii) emotional conducts; and (iii) glial activity and expression of inducible nitric oxide synthase (NOS2), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), and antioxidant enzymes (heme oxygenase 1, NAD(P)H:quinone oxidoreductase-1, glutathione S-transferase mu 1 and alpha 1) in the hippocampus. The administration of A-ITC and P-ITC inhibited the mechanical allodynia, the grip strength deficits, and the depressive-like behaviors accompanying osteoarthritis. Both treatments inhibited microglial activation, normalized the upregulation of NOS2 and PI3K/p-Akt, and maintained high levels of antioxidant/detoxificant enzymes in the hippocampus. Data suggest that treatment with low doses of slow-releasing H2S donors might be an interesting strategy for the treatment of nociception, functional disability, and emotional disorders associated with osteoarthritis pain.

Treatment with slow-releasing hydrogen sulfide donors inhibits the nociceptive and depressive-like behaviours accompanying chronic neuropathic pain: Endogenous antioxidant system activation

2020 ◽  
Vol 34 (7) ◽  
pp. 737-749 ◽  
Author(s):  
Laura Cabarga ◽  
Gerard Batallé ◽  
Olga Pol
Keyword(s):  
Neuropathic Pain ◽  
Hydrogen Sulfide ◽  
Emotional Disorders ◽  
Intraperitoneal Administration ◽  
Thermal Hyperalgesia ◽  
Allyl Isothiocyanate ◽  
Phenyl Isothiocyanate ◽  
Heme Oxygenase 1 ◽  
Chronic Neuropathic Pain ◽  
Endogenous Antioxidant

Background: Therapies to treat chronic neuropathic pain and its associated comorbidities are limited. Recent studies demonstrated that the administration of slow-releasing hydrogen sulfide (H2S) donors inhibited chemotherapy-induced neuropathic pain. However, the antidepressant or anxiolytic effects of these compounds and their mechanisms of action during chronic neuropathic pain have not been evaluated. Aims: To determine whether the administration of two slow-releasing H2S donors, allyl isothiocyanate (A-ITC) and phenyl isothiocyanate (P-ITC), inhibits the nociceptive and emotional disorders associated with chronic neuropathic pain. Methods: In C57BL/6 male mice with neuropathic pain caused by the chronic constriction of the sciatic nerve, we assessed the effects of intraperitoneal administration of A-ITC and P-ITC in (a) the mechanical allodynia, thermal hyperalgesia and thermal allodynia induced by nerve ligation; (b) the anxiety- and depressive-like behaviours linked with neuropathic pain; (c) glial activation and mitogen-activated protein kinases phosphorylation, and (d) expression of the antioxidant enzymes, heme oxygenase 1 (HO-1), NADPH quinone oxidoreductase1, and glutathione S-transferase mu-1 (GSTM1), and alpha-1 (GSTA1), in hippocampus and prefrontal cortex (PFC). Results: Both treatments inhibited the allodynia and hyperalgesia, depressive-like behaviours, astroglial activation, and the extracellular signal-regulated kinase 1/2 phosphorylation but were unable to abolish the anxiety-like behaviours accompanying neuropathic pain. A-ITC and P-ITC also augmented the expression of HO-1, GSTM1, and GSTA1 in the hippocampus and/or PFC. Conclusions: The administration of slow-releasing H2S donors might be a promising treatment for the management of chronic neuropathic pain and some associated comorbidities via inhibiting the inflammatory and plasticity changes, and activating the endogenous antioxidant responses.

scholarly journals The Recovery of Cognitive and Affective Deficiencies Linked with Chronic Osteoarthritis Pain and Implicated Pathways by Slow-Releasing Hydrogen Sulfide Treatment

Antioxidants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1632
Author(s):  
Gerard Batallé ◽  
Xue Bai ◽  
Enric Pouso-Vázquez ◽  
Gerad Roch ◽  
Laura Rodríguez ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Grip Strength ◽  
Gray Matter ◽  
Periaqueductal Gray ◽  
Anterior Cingulate ◽  
Diallyl Disulfide ◽  
Infralimbic Cortex ◽  
Periaqueductal Gray Matter ◽  
Osteoarthritis Pain ◽  
Osteoarthritic Pain

Chronic osteoarthritis pain is accompanied by several comorbidities whose treatment has not been completely resolved. The anti-inflammatory, analgesic, and antidepressant effects of slow-releasing hydrogen sulfide (H2S) donors during osteoarthritic pain have been shown, but their actions in the accompanying memory impairment and anxious-like behaviors have not yet been demonstrated. Using female mice with chronic osteoarthritic pain, the effects of natural, diallyl disulfide (DADS) or synthetic, morpholin-4-ium 4-methoxyphenyl(morpholino) phosphinodithioate dichloromethane complex (GYY4137) slow-releasing H2S donors, on associated cognitive and grip strength deficits and anxiodepressive-like behaviors, were assessed. Their effects on specific brain areas implicated in the modulation of pain and emotional responses were also determined. Results demonstrated an improvement in memory and grip strength deficits, as well as in the anxious-like behaviors associated with chronic pain in GYY4137 and/or DADS treated mice. The painkiller and antidepressant properties of both treatments were also established. Treatment with DADS and/or GYY4137 inhibited: oxidative stress in the amygdala; phosphoinositide 3-kinase overexpression in the amygdala, periaqueductal gray matter, and anterior cingulate cortex; protein kinase B activation in the amygdala and infralimbic cortex; up-regulation of inducible nitric oxide synthase in the amygdala, periaqueductal gray matter and infralimbic cortex and apoptotic responses in the amygdala. These results might explain the recovery of memory and grip strength and the inhibition of allodynia and associated anxiodepressive-like behaviors by these treatments. In conclusion, this study revealed new properties of slow-releasing H2S donors in cognitive impairment and affective disorders linked with chronic osteoarthritis pain and their effects on the central nervous system.

scholarly journals MZe786, a hydrogen sulfide-releasing aspirin prevents preeclampsia in heme oxygenase-1 haplodeficient pregnancy under high soluble flt-1 environment

Redox Biology ◽  
2021 ◽  
Vol 38 ◽  
pp. 101768 ◽  
Author(s):  
Homira Rezai ◽  
Shakil Ahmad ◽  
Faisal A. Alzahrani ◽  
Lissette Sanchez-Aranguren ◽  
Irundika HK. Dias ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Heme Oxygenase ◽  
Heme Oxygenase 1

scholarly journals Analgesic and Antidepressant Effects of Oltipraz on Neuropathic Pain in Mice by Modulating Microglial Activation

2019 ◽  
Vol 8 (6) ◽  
pp. 890 ◽  
Author(s):  
Andrés Felipe Díaz ◽  
Sara Polo ◽  
Núria Gallardo ◽  
Sergi Leánez ◽  
Olga Pol
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Prefrontal Cortex ◽  
Emotional Disorders ◽  
Microglial Activation ◽  
Antioxidant Properties ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nuclear Factor ◽  
Antidepressant Effects

Nerve injury provokes microglial activation, contributing to the sensory and emotional disorders associated with neuropathic pain that do not completely resolve with treatment. In C57BL/6J mice with neuropathic pain induced by chronic constriction of the sciatic nerve (CCI), we evaluated the effects of oltipraz, an antioxidant and anticancer compound, on (1) allodynia and hyperalgesia, (2) microglial activation and pain signaling pathways, (3) oxidative stress, and (4) depressive-like behaviors. Twenty-eight days after surgery, we assessed the effects of oltipraz on the expression of CD11b/c (a microglial marker), phosphoinositide 3-kinase (PI3K)/ phosphorylated protein kinase B (p-Akt), nuclear factor-κB (NF-κB) transcription factor, and mitogen activated protein kinases (MAPK) in the spinal cord, hippocampus, and prefrontal cortex. Our results show that oltipraz alleviates neuropathic pain by inhibiting microglial activation and PI3K/p-Akt, phosphorylated inhibitor of κBα (p-IκBα), and MAPK overexpression, and by normalizing and/or enhancing the expression of antioxidant proteins, nuclear factor erythroid derived-2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), and NAD(P)H:quinone oxidoreductase-1 (NQO1) in the spinal cord. The inhibition of microglial activation and induction of the Nrf2/HO-1/NQO1 signaling pathway in the hippocampus and/or prefrontal cortex may explain the antidepressant effects of oltipraz during neuropathic pain. These data demonstrate the analgesic and antidepressant effects of oltipraz and reveal its protective and antioxidant properties during chronic pain.

scholarly journals Allyl Isothiocyanate Protects Acetaminophen-Induced Liver Injury via NRF2 Activation by Decreasing Spontaneous Degradation in Hepatocyte

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3585
Author(s):  
Min Woo Kim ◽  
Ju-Hee Kang ◽  
Hyun Jin Jung ◽  
Se Yong Park ◽  
Thu Han Le Phan ◽  
...  
Keyword(s):  
Target Genes ◽  
Nuclear Translocation ◽  
Biological Effects ◽  
Allyl Isothiocyanate ◽  
Heme Oxygenase 1 ◽  
Toxic Metabolite ◽  
Related Factor ◽  
Dependent Manner ◽  
Nrf2 Activation ◽  
Nrf2 Target Gene

Acetaminophen (APAP) is one of the most frequently prescribed analgesic and anti-pyretic drugs. However, APAP-induced hepatotoxicity is a major cause of acute liver failure globally. While the therapeutic dose is safe, an overdose of APAP produces an excess of the toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI), subsequently resulting in hepatotoxicity. Allyl isothiocyanate (AITC), a bioactive molecule in cruciferous plants, is reported to exert various biological effects, including anti-inflammatory, anti-cancer, and anti-microbial effects. Notably, AITC is known for activating nuclear factor erythroid 2-related factor 2 (NRF2), but there is limited evidence supporting the beneficial effects on hepatocytes and liver, where AITC is mainly metabolized. We applied a mouse model in the current study to investigate whether AITC protects the liver against APAP-induced injury, wherein we observed the protective effects of AITC. Furthermore, NRF2 nuclear translocation and the increase of target genes by AITC treatment were confirmed by in vitro experiments. APAP-induced cell damage was attenuated by AITC via an NRF2-dependent manner, and rapid NRF2 activation by AITC was attributed to the elevation of NRF2 stability by decreasing its spontaneous degradation. Moreover, liver tissues from our mouse experiment revealed that AITC increases the expression of heme oxygenase-1 (HO-1), an NRF2 target gene, confirming the potential of AITC as a hepatoprotective agent that induces NRF2 activation. Taken together, our results indicate the potential of AITC as a natural-product-derived NRF2 activator targeting the liver.

Radioprotective Activity of Naturally Occurring Organosulfur Compounds

2006 ◽  
Vol 92 (2) ◽  
pp. 163-169 ◽  
Author(s):  
Manesh Chittezhath ◽  
Girija Kuttan
Keyword(s):  
Intestinal Mucosa ◽  
Lipid Peroxides ◽  
Allyl Isothiocyanate ◽  
Sulfur Compounds ◽  
Whole Body ◽  
Phenyl Isothiocyanate ◽  
Histopathological Analysis ◽  
Diallyl Disulfide ◽  
Organosulfur Compounds ◽  
Naturally Occurring

The radioprotective effects of naturally occurring sulfur compounds and isothiocyanates such as diallyl sulfide (DAS), diallyl disulfide (DADS), allyl methyl sulfide (AMS), allyl isothiocyanate (AITC) and phenyl isothiocyanate (PITC) have been investigated in whole body irradiated Swiss albino mice. Administration of these sulfur compounds could reduce the serum content of alkaline phosphatase (ALP), which was elevated after irradiation (23.9 ± 1.82 KA units). The elevated liver content of glutamate pyruvate transaminase (GPT) in control animals (76.2 ± 2.2 U/mL) after irradiation was significantly reduced in DAS (58.93 ± 4 U/mL) and AMS (55.7 ± 2.2 U/mL) treated animals. Elevated levels of lipid peroxides in serum and liver of irradiated control animals were also significantly reduced by treatment with these sulfur compounds. The glutathione (GSH) content in liver and intestinal mucosa was drastically reduced after irradiation. All the sulfur compounds and isothiocyanates could effectively enhance the GSH content of intestinal mucosa and liver. Findings at histopathological analysis of the intestine proved to be correlated with the above results.

scholarly journals Safety and efficacy of a new micronized formulation of the ALIAmide palmitoylglucosamine in preclinical models of inflammation and osteoarthritis pain

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Marika Cordaro ◽  
Rosalba Siracusa ◽  
Daniela Impellizzeri ◽  
Ramona D’ Amico ◽  
Alessio Filippo Peritore ◽  
...  
Keyword(s):  
Mast Cells ◽  
Mechanical Allodynia ◽  
Thermal Hyperalgesia ◽  
Myeloperoxidase Activity ◽  
Post Injection ◽  
Protective Effects ◽  
Oral Toxicity ◽  
Particle Size Reduction ◽  
Radiographic Damage ◽  
Osteoarthritis Pain

Abstract Background Osteoarthritis is increasingly recognized as the result of a complex interplay between inflammation, chrondrodegeneration, and pain. Joint mast cells are considered to play a key role in orchestrating this detrimental triad. ALIAmides down-modulate mast cells and more generally hyperactive cells. Here we investigated the safety and effectiveness of the ALIAmide N-palmitoyl-d-glucosamine (PGA) in inflammation and osteoarthritis pain. Methods Acute toxicity of micronized PGA (m-PGA) was assessed in rats following OECD Guideline No.425. PGA and m-PGA (30 mg/kg and 100 mg/kg) were orally administered to carrageenan (CAR)-injected rats. Dexamethasone 0.1 mg/kg was used as reference. Paw edema and thermal hyperalgesia were measured up to 6 h post-injection, when also myeloperoxidase activity and histological inflammation score were assessed. Rats subjected to intra-articular injection of sodium monoiodoacetate (MIA) were treated three times per week for 21 days with PGA or m-PGA (30 mg/kg). Mechanical allodynia and motor function were evaluated at different post-injection time points. Joint histological and radiographic damage was scored, articular mast cells were counted, and macrophages were immunohistochemically investigated. Levels of TNF-α, IL-1β, NGF, and MMP-1, MMP-3, and MMP-9 were measured in serum using commercial colorimetric ELISA kits. One- or two-way ANOVA followed by a Bonferroni post hoc test for multiple comparisons was used. Results Acute oral toxicity of m-PGA resulted in LD50 values in excess of 2000 mg/kg. A single oral administration of PGA and m-PGA significantly reduced CAR-induced inflammatory signs (edema, inflammatory infiltrate, and hyperalgesia), and m-PGA also reduced the histological score. Micronized PGA resulted in a superior activity to PGA on MIA-induced mechanical allodynia, locomotor disability, and histologic and radiographic damage. The MIA-induced increase in mast cell count and serum level of the investigated markers was also counteracted by PGA and to a significantly greater extent by m-PGA. Conclusions The results of the present study showed that PGA is endorsed with anti-inflammatory, pain-relieving, and joint-protective effects. Moreover, it proved that particle size reduction greatly enhances the activity of PGA, particularly on joint pain and disability. Given these results, m-PGA could be considered a valuable option in the management of osteoarthritis.

scholarly journals Mitochondria-targeted heme oxygenase-1 decreases oxidative stress in renal epithelial cells

2013 ◽  
Vol 305 (3) ◽  
pp. F255-F264 ◽  
Author(s):  
Subhashini Bolisetty ◽  
Amie Traylor ◽  
Abolfazl Zarjou ◽  
Michelle S. Johnson ◽  
Gloria A. Benavides ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Heme Oxygenase ◽  
Manganese Superoxide Dismutase ◽  
Negative Impact ◽  
Tricarboxylic Acid Cycle ◽  
Mitochondrial Fraction ◽  
Hek293 Cells ◽  
Heme Oxygenase 1 ◽  
Protective Mechanism

Mitochondria are both a source and target of the actions of reactive oxygen species and possess a complex system of inter-related antioxidants that control redox signaling and protect against oxidative stress. Interestingly, the antioxidant enzyme heme oxygenase-1 (HO-1) is not present in the mitochondria despite the fact that the organelle is the site of heme synthesis and contains multiple heme proteins. Detoxification of heme is an important protective mechanism since the reaction of heme with hydrogen peroxide generates pro-oxidant ferryl species capable of propagating oxidative stress and ultimately cell death. We therefore hypothesized that a mitochondrially localized HO-1 would be cytoprotective. To test this, we generated a mitochondria-targeted HO-1 cell line by transfecting HEK293 cells with a plasmid construct containing the manganese superoxide dismutase mitochondria leader sequence fused to HO-1 cDNA (Mito-HO-1). Nontargeted HO-1-overexpressing cells were generated by transfecting HO-1 cDNA (HO-1) or empty vector (Vector). Mitochondrial localization of HO-1 with increased HO activity in the mitochondrial fraction of Mito-HO-1 cells was observed, but a significant decrease in the expression of heme-containing proteins occurred in these cells. Both cytosolic HO-1- and Mito-HO-1-expressing cells were protected against hypoxia-dependent cell death and loss of mitochondrial membrane potential, but these effects were more pronounced with Mito-HO-1. Furthermore, decrement in production of tricarboxylic acid cycle intermediates following hypoxia was significantly mitigated in Mito-HO-1 cells. These data suggest that specific mitochondrially targeted HO-1 under acute pathological conditions may have beneficial effects, but the selective advantage of long-term expression is constrained by a negative impact on the synthesis of heme-containing mitochondrial proteins.

Post-stroke quality of life and depression

2002 ◽  
Vol 14 (5) ◽  
pp. 219-225 ◽  
Author(s):  
Krystyna Jaracz ◽  
Jan Jaracz ◽  
Wojciech Kozubski ◽  
Janusz K Rybakowski
Keyword(s):  
Quality Of Life ◽  
Emotional Support ◽  
Functional Disability ◽  
Negative Impact ◽  
Physical Dependence ◽  
Well Being ◽  
Post Stroke ◽  
Polish Version ◽  
Quality Of Life Index

Background:Studies on the determinants of the quality of life (QOL) after stroke bring differing results depending on the applied concept of QOL. This may lead to confusion about the contribution of various factors to the post-stroke QOL.Objective:The aim of the study was: (i) to investigate functional and psychological QOL in the individuals after the first ischemic stroke; (ii) to identify the most important correlates of QOL; and (iii) to examine the significance of depression among the other possible predictors of QOL.Methods:A hospital-based sample of 72 stroke patients was followed up to 6 months after stroke onset. QOL was assessed using the Polish version of the Quality of Life Index and the Sickness Impact Profile. A multiple regression procedure was performed to examine relationships between QOL and the study variables.Results:In spite of good recovery, the psychological and functional QOL of the examined patients was impaired, although the negative impact of stroke was greater on the objective QOL than on the subjective QOL. Stroke-related impairment, depression, functional disability and marital status predicted 80% of the variance in the functional QOL. Emotional support, depression and functional disability explained 38% of the variance in psychological well-being.Conclusions:Depression and physical disability were the most important predictors of QOL after stroke since their impact on QOL was more robust in comparison to the remaining variables. For improving QOL, a comprehensive care for patients aimed at reducing physical dependence and ameliorating depressive symptoms could be recommended.

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