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Article: The Impact of CB1 Receptor on Inflammation in Skeletal Muscle Cells.

Haddad, Mansour

2021 Volume 14, Page(s) 3959–3967

Abstract: Background: Various factors trigger the inflammatory response and cytokine activation in skeletal muscle. Inflamed muscle will exhibit significant levels of inflammation and cytokine activity. Interleukin-6 (IL-6), a pro-inflammatory cytokine, exerts ... ...

Abstract	Background: Various factors trigger the inflammatory response and cytokine activation in skeletal muscle. Inflamed muscle will exhibit significant levels of inflammation and cytokine activity. Interleukin-6 (IL-6), a pro-inflammatory cytokine, exerts pleiotropic effects on skeletal muscle. Endocannabinoid produced by all cell types binds to a class of G protein-coupled receptors, in particular cannabinoid CB1 receptors, to induce skeletal muscle actions. Objective: The purpose of this research was to discover whether activation of cannabinoid CB1 receptors in L6 skeletal muscle cells may promote IL-6 gene expression. Materials and methods: L6 skeletal muscle cells were cultured in 25 cm Results: Arachidonyl-2'-chloroethylamide (ACEA) 10 nM, a persistent selective CB1 receptor agonist, promotes IL-6 gene expression in a time-dependent manner. Rimonabant 100 nM, a selective cannabinoid CB1 receptor antagonist, blocks the impact of ACEA. However, insulin does not change IL-6 gene expression. Conclusion: For the first time, a unique link between ACEA and IL-6 up-regulation has been established; IL-6 up-regulation generated by ACEA is mediated in skeletal muscle through cannabinoid CB1 receptor activation. As a result, cannabinoid CB1 receptors may be useful pharmaceutical targets in the treatment of inflammation and related disorders in skeletal muscle tissues.
Language	English
Publishing date	2021-08-14
Publishing country	New Zealand
Document type	Journal Article
ZDB-ID	2494878-0
ISSN	1178-7031
ISSN	1178-7031
DOI	10.2147/JIR.S322247
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Article ; Online: Impact of Adenosine Analogue, Adenosine-5'-N-Ethyluronamide (NECA), on Insulin Signaling in Skeletal Muscle Cells.

Haddad, Mansour

BioMed research international

2021 Volume 2021, Page(s) 9979768

Abstract: Materials and methods: Rat L6 skeletal muscle cells were cultured in 25 cm: Results: Adenosine-5'-N-ethyluronamide (NECA), a stable adenosine analogue, significantly stimulate inflammatory mediator (IL-6) (: Conclusions: A novel crosstalk between ... ...

Abstract	Materials and methods: Rat L6 skeletal muscle cells were cultured in 25 cm Results: Adenosine-5'-N-ethyluronamide (NECA), a stable adenosine analogue, significantly stimulate inflammatory mediator (IL-6) ( Conclusions: A novel crosstalk between adenosine analogue and insulin has been demonstrated for the first time; evidence has been gathered in vitro for the effects of NECA and insulin treatment on intracellular signaling pathways, in particular glycolysis and insulin sensitivity in skeletal muscle cells.
MeSH term(s)	Acetyl-CoA Carboxylase/metabolism ; Acyl-CoA Dehydrogenase, Long-Chain/metabolism ; Adenosine/analogs & derivatives ; Adenosine/metabolism ; Adenosine-5'-(N-ethylcarboxamide)/pharmacology ; Animals ; Carnitine O-Palmitoyltransferase/metabolism ; Hexokinase/metabolism ; Inflammation ; Insulin/metabolism ; Interleukin-6/metabolism ; Muscle Fibers, Skeletal/metabolism ; Muscle, Skeletal/cytology ; Muscle, Skeletal/metabolism ; Myoblasts/metabolism ; Nuclear Receptor Subfamily 4, Group A, Member 1/metabolism ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism ; Phosphofructokinases/metabolism ; Pyruvate Dehydrogenase Acetyl-Transferring Kinase/metabolism ; Rats ; Receptors, Cytoplasmic and Nuclear/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction/drug effects ; Transcription Factors/genetics
Chemical Substances	Insulin ; Interleukin-6 ; Nr4a1 protein, rat ; Nuclear Receptor Subfamily 4, Group A, Member 1 ; Pdk4 protein, rat ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; Ppargc1a protein, rat ; Pyruvate Dehydrogenase Acetyl-Transferring Kinase ; Receptors, Cytoplasmic and Nuclear ; Transcription Factors ; Adenosine-5'-(N-ethylcarboxamide) (35920-39-9) ; Acyl-CoA Dehydrogenase, Long-Chain (EC 1.3.8.8) ; CPT1b protein, rat (EC 2.3.1.21) ; Carnitine O-Palmitoyltransferase (EC 2.3.1.21) ; Phosphofructokinases (EC 2.7.1 -) ; Hexokinase (EC 2.7.1.1) ; Acetyl-CoA Carboxylase (EC 6.4.1.2) ; Adenosine (K72T3FS567)
Language	English
Publishing date	2021-06-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	2698540-8
ISSN	2314-6141 ; 2314-6133
ISSN (online)	2314-6141
ISSN	2314-6133
DOI	10.1155/2021/9979768
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Article ; Online: The Impact of CB1 Receptor on Nuclear Receptors in Skeletal Muscle Cells.

Haddad, Mansour

Pathophysiology : the official journal of the International Society for Pathophysiology

2021 Volume 28, Issue 4, Page(s) 457–470

Abstract: Cannabinoids are abundant signaling compounds; their influence predominantly arises via engagement with the principal two G-protein-coupled cannabinoid receptors, CB1 and CB2. One suggested theory is that cannabinoids regulate a variety of physiological ... ...

Abstract	Cannabinoids are abundant signaling compounds; their influence predominantly arises via engagement with the principal two G-protein-coupled cannabinoid receptors, CB1 and CB2. One suggested theory is that cannabinoids regulate a variety of physiological processes within the cells of skeletal muscle. Earlier publications have indicated that expression of CB1 receptor mRNA and protein has been recognized within myotubes and tissues of skeletal muscle from both murines and humans, thus representing a potentially significant pathway which plays a role in the control of skeletal muscular activities. The part played by CB1 receptor activation or inhibition with respect to these functions and relevant to targets in the periphery, especially skeletal muscle, is not fully delineated. Thus, the aim of the current research was to explore the influence of CB1 receptor stimulation and inhibition on downstream signaling of the nuclear receptor, NR4A, which regulates the immediate impacts of arachidonyl-2'-chloroethylamide (ACEA) and/or rimonabant in the cells of skeletal muscle. Murine L6 skeletal muscle cells were used in order to clarify additional possible molecular signaling pathways which contribute to alterations in the CB1 receptor. Skeletal muscle cells have often been used; it is well-documented that they express cannabinoid receptors. Quantitative real-time probe-based polymerase chain reaction (qRT-PCR) assays are deployed in order to assess the gene expression characteristics of CB1 receptor signaling. In the current work, it is demonstrated that skeletal muscle cells exhibit functional expression of CB1 receptors. This can be deduced from the qRT-PCR assays; triggering CB1 receptors amplifies both NR4A1 and NR4A3 mRNA gene expression. The impact of ACEA is inhibited by the selective CB1 receptor antagonist, rimonabant. The present research demonstrated that 10 nM of ACEA notably amplified mRNA gene expression of NR4A1 and NR4A3; this effect was suppressed by the addition of 100 nM rimonabant. Furthermore, the CB1 receptor antagonist led to the downregulation of mRNA gene expression of NR4A1, NR4A2 and NR4A3. In conclusion, in skeletal muscle, CB1 receptors were recognized to be important moderators of NR4A1 and NR4A3 mRNA gene expression; these actions may have possible clinical benefits. Thus, in skeletal muscle cells, a possible physiological expression of CB1 receptors was identified. It is as yet unknown whether these CB1 receptors contribute to pathways underlying skeletal muscle biological function and disease processes. Further research is required to fully delineate their role(s).
Language	English
Publishing date	2021-10-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1212740-1
ISSN	1873-149X ; 0928-4680
ISSN (online)	1873-149X
ISSN	0928-4680
DOI	10.3390/pathophysiology28040029
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Article ; Online: Targeting therapy-induced senescence as a novel strategy to combat chemotherapy-induced peripheral neuropathy.

Alsalem, Mohammad / Ellaithy, Amr / Bloukh, Sarah / Haddad, Mansour / Saleh, Tareq

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer

2024 Volume 32, Issue 1, Page(s) 85

Abstract: Chemotherapy-induced peripheral neuropathy (CIPN) is a treatment-limiting adverse effect of anticancer therapy that complicates the lifestyle of many cancer survivors. There is currently no gold-standard for the assessment or management of CIPN. ... ...

Abstract	Chemotherapy-induced peripheral neuropathy (CIPN) is a treatment-limiting adverse effect of anticancer therapy that complicates the lifestyle of many cancer survivors. There is currently no gold-standard for the assessment or management of CIPN. Subsequently, understanding the underlying mechanisms that lead to the development of CIPN is essential for finding better pharmacological therapy. Therapy-induced senescence (TIS) is a form of senescence that is triggered in malignant and non-malignant cells in response to the exposure to chemotherapy. Recent evidence has also suggested that TIS develops in the dorsal root ganglia of rodent models of CIPN. Interestingly, several components of the senescent phenotype are commensurate with the currently established primary processes implicated in the pathogenesis of CIPN including mitochondrial dysfunction, oxidative stress, and neuroinflammation. In this article, we review the literature that supports the hypothesis that TIS could serve as a holistic mechanism leading to CIPN, and we propose the potential for investigating senotherapeutics as means to mitigate CIPN in cancer survivors.
MeSH term(s)	Humans ; Antineoplastic Agents/adverse effects ; Peripheral Nervous System Diseases/pathology ; Cancer Survivors ; Oxidative Stress
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2024-01-05
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	1134446-5
ISSN	1433-7339 ; 0941-4355
ISSN (online)	1433-7339
ISSN	0941-4355
DOI	10.1007/s00520-023-08287-0
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Zs.A 3697: Show issues

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Article ; Online: Adenosine A2B Receptors - Mediated Induction of Interleukin-6 in Skeletal Muscle Cells.

Haddad, Mansour

Turkish journal of pharmaceutical sciences

2017 Volume 14, Issue 1, Page(s) 19–28

Abstract: Objectives: Inflammatory response and cytokine activation are markedly stimulated in skeletal muscle during various conditions. Interleukin-6 (IL-6), a pro-inflammatory cytokine, has pleiotropic effects on skeletal muscle. Adenosine, released by all ... ...

Abstract	Objectives: Inflammatory response and cytokine activation are markedly stimulated in skeletal muscle during various conditions. Interleukin-6 (IL-6), a pro-inflammatory cytokine, has pleiotropic effects on skeletal muscle. Adenosine, released by all cell types, binds to a class of G protein-coupled receptors to induce various skeletal muscle effects. The aim of this work was to investigate whether activation of adenosine receptors, particularly adenosine A2B receptors, could stimulate IL-6 gene expression in rat L6 skeletal muscle cells. Materials and methods: The rat L6 skeletal muscle cells were cultured in 25 cm Results: Adenosine-5'- Conclusion: Here, a novel relationship between adenosine and IL-6 up-regulation has been demonstrated for the first time; IL-6 up-regulation induced by NECA is mediated by adenosine A2B receptor activation in skeletal muscle and is dependent on mainly a cAMP pathway. Adenosine A2B receptors are, thus, potentially important pharmacological targets in treating inflammation and related diseases in skeletal muscle tissues.
Language	English
Publishing date	2017-04-15
Publishing country	Turkey
Document type	Journal Article
ZDB-ID	2238484-4
ISSN	2148-6247 ; 2148-6247
ISSN (online)	2148-6247
ISSN	2148-6247
DOI	10.4274/tjps.08108
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Article ; Online: A Versatile, Functional Group-Tolerant, and Bench-Stable Iron Precatalyst for Building Arene and Triazine Rings by [2+2+2] Cycloadditions.

Parisot, William / Haddad, Mansour / Phansavath, Phannarath / Lefèvre, Guillaume / Ratovelomanana-Vidal, Virginie

Chemistry (Weinheim an der Bergstrasse, Germany)

2024 Volume 30, Issue 22, Page(s) e202400096

Abstract: We report an efficient iron-catalyzed cycloaddition procedure leading to the construction of (hetero)aromatic rings by alkyne [2+2+2] cycloisomerization. This method relies on the use of an air-stable (N,N)Fe(II) precursor easily prepared from a ... ...

Abstract	We report an efficient iron-catalyzed cycloaddition procedure leading to the construction of (hetero)aromatic rings by alkyne [2+2+2] cycloisomerization. This method relies on the use of an air-stable (N,N)Fe(II) precursor easily prepared from a commercially available ligand derived from 1,10-phenanthroline, reduced in situ into a catalytically active non-innocent (N,N ⋅
Language	English
Publishing date	2024-02-28
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1478547-X
ISSN	1521-3765 ; 0947-6539
ISSN (online)	1521-3765
ISSN	0947-6539
DOI	10.1002/chem.202400096
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Article ; Online: Adenosine Receptors as Potential Therapeutic Analgesic Targets.

Haddad, Mansour / Cherchi, Federica / Alsalem, Mohammad / Al-Saraireh, Yousef M / Madae'en, Saba

International journal of molecular sciences

2023 Volume 24, Issue 17

Abstract: Pain represents an international burden and a major socio-economic public health problem. New findings, detailed in this review, suggest that adenosine plays a significant role in neuropathic and inflammatory pain, by acting on its metabotropic adenosine ...

Abstract	Pain represents an international burden and a major socio-economic public health problem. New findings, detailed in this review, suggest that adenosine plays a significant role in neuropathic and inflammatory pain, by acting on its metabotropic adenosine receptors (A
MeSH term(s)	Humans ; Ligands ; Analgesics/pharmacology ; Analgesics/therapeutic use ; Pain/drug therapy ; Adenosine/therapeutic use ; Receptors, Purinergic P1
Chemical Substances	Ligands ; Analgesics ; Adenosine (K72T3FS567) ; Receptors, Purinergic P1
Language	English
Publishing date	2023-08-24
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241713160
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Article ; Online: Interaction of the synthetic cannabinoid WIN55212 with tramadol on nociceptive thresholds and core body temperature in a chemotherapy-induced peripheral neuropathy pain model.

Haddad, Mansour / Alsalem, Mohammad / Saleh, Tareq / Jaffal, Sahar M / Barakat, Noor A / El-Salem, Khalid

Neuroreport

2023 Volume 34, Issue 8, Page(s) 441–448

Abstract: Chemotherapy-induced peripheral neuropathy (CIPN) is a significant adverse effect of many anticancer drugs. Current strategies for the management of CIPN pain are still largely unmet. The aim of this study is to investigate the antinociceptive potential ... ...

Abstract	Chemotherapy-induced peripheral neuropathy (CIPN) is a significant adverse effect of many anticancer drugs. Current strategies for the management of CIPN pain are still largely unmet. The aim of this study is to investigate the antinociceptive potential of combining tramadol with the synthetic cannabinoid WIN55212, and to evaluate their associated adverse effects, separately or in combination, in a CIPN rat model, and to investigate their ability to modulate the transient receptor potential vanilloid 1 (TRPV1) receptor activity. Von Frey filaments were used to determine the paw withdrawal threshold in adult male Sprague-Dawley rats (200-250 g) following intraperitoneal (i.p) injection of cisplatin. Single cell ratiometric calcium imaging was used to investigate WIN55212/tramadol combination ability to modulate the TRPV1 receptor activity. Both tramadol and WIN55212 produced dose-dependent antinociceptive effect when administered separately. The lower dose of tramadol (1 mg/kg) significantly enhanced the antinociceptive effects of WIN55212 without interfering with core body temperature. Mechanistically, capsaicin (100 nM) produced a robust increase in [Ca 2+ ] i in dorsal root ganglia (DRG) neurons ex vivo . Capsaicin-evoked calcium responses were significantly reduced upon pre-incubation of DRG neurons with only the highest concentration of tramadol (10 µM), but not with WIN55212 at any concentration (0.1, 1 and 10 µM). However, combining sub-effective doses of WIN55212 (1 µM) and tramadol (0.1 µM) produced a significant inhibition of capsaicin-evoked calcium responses. Combining WIN55212 with tramadol shows better antinociceptive effects with no increased risk of hypothermia, and provides a potential pain management strategy for CIPN.
MeSH term(s)	Rats ; Male ; Animals ; Tramadol/pharmacology ; Rats, Sprague-Dawley ; Capsaicin/pharmacology ; Calcium ; Nociception ; Body Temperature ; Pain ; Peripheral Nervous System Diseases/chemically induced ; Peripheral Nervous System Diseases/drug therapy ; Cannabinoids/pharmacology ; Antineoplastic Agents/pharmacology ; Analgesics/pharmacology ; Analgesics/therapeutic use ; Ganglia, Spinal
Chemical Substances	Tramadol (39J1LGJ30J) ; Capsaicin (S07O44R1ZM) ; Calcium (SY7Q814VUP) ; Cannabinoids ; Antineoplastic Agents ; Analgesics
Language	English
Publishing date	2023-04-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1049746-8
ISSN	1473-558X ; 0959-4965
ISSN (online)	1473-558X
ISSN	0959-4965
DOI	10.1097/WNR.0000000000001910
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Zs.A 3118: Show issues

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ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Assessment of Alfalfa (Medicago sativa L.) Cultivars for Salt Tolerance Based on Yield, Growth, Physiological, and Biochemical Traits

Guiza, Maroua / Benabdelrahim, Mohammed Ali / Brini, Faical / Haddad, Mansour / Saibi, Walid

J Plant Growth Regul. 2022 Dec., v. 41, no. 8 p.3117-3126

2022

Abstract: Alfalfa (Medicago sativa L.) is one of the most valuable forage crops having an intermediate salt-tolerant level. In this fact, twelve selected alfalfa from the south Tunisia oasis were subjected to salt stress looking for their adaptability against ... ...

Abstract	Alfalfa (Medicago sativa L.) is one of the most valuable forage crops having an intermediate salt-tolerant level. In this fact, twelve selected alfalfa from the south Tunisia oasis were subjected to salt stress looking for their adaptability against these abiotic constraints. Hence, this work reports the sodium chloride effect (150 mM) on the basis of biomass yield reduction. For this, some cultural, physiological, and biochemical parameters were monitored. Indeed, the relative water content, the stem and leaves aspects, chlorophyll content, protein amount, free proline amount, K⁺ and Na⁺ concentrations, protease and α-amylase activities, superoxide dismutase, and catalase ones were monitored. The findings give rise to no significant salinity effect on stem length and leaf number. However, there was a significant difference in leaf color for plants under salt stress. In addition, salinity decreases both fresh and dry weight of all cultivars. NaCl treatment significantly reduced chlorophyll content and the K⁺ ion accumulations. Also, under salt stress, there was higher proline accumulation, Na⁺, and proteins in all alfalfa cultivars than under control. Additionally, these findings noticed the increase of enzymatic scavenging system related to the activity of superoxide dismutase, catalase, and protease under salt stress condition. In contrast, the α-amylase activity decreased under salt treatment. It seems from the studied parameters that our 12 alfalfa oasis cultivars are tolerant to salt stress under oasis conditions.
Keywords	Medicago sativa ; alfalfa ; alpha-amylase ; biomass production ; catalase ; chlorophyll ; color ; cultivars ; forage ; leaves ; oases ; plant growth ; proline ; proteinases ; salinity ; salt stress ; salt tolerance ; sodium chloride ; superoxide dismutase ; water content ; Tunisia
Language	English
Dates of publication	2022-12
Size	p. 3117-3126.
Publishing place	Springer US
Document type	Article ; Online
ZDB-ID	586787-3
ISSN	1435-8107 ; 0721-7595
ISSN (online)	1435-8107
ISSN	0721-7595
DOI	10.1007/s00344-021-10499-9
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Synthesis of Benzo[

Huvelle, Steve / Matton, Pascal / Tran, Christine / Rager, Marie-Noelle / Haddad, Mansour / Ratovelomanana-Vidal, Virginie

Organic letters

2022 Volume 24, Issue 28, Page(s) 5126–5131

Abstract: A convenient method for the ruthenium-catalyzed synthesis of benzo[ ...

Abstract	A convenient method for the ruthenium-catalyzed synthesis of benzo[
Language	English
Publishing date	2022-07-11
Publishing country	United States
Document type	Journal Article
ISSN	1523-7052
ISSN (online)	1523-7052
DOI	10.1021/acs.orglett.2c01963
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