Review
Pharmacology & Pharmacy
Nicola Bauer, Zhengnan Yuan, Xiaoxiao Yang, Binghe Wang
Summary: Carbon monoxide (CO) is a signaling molecule with pharmacological effects. Four carbonyl complexes called CO-releasing molecules (CORMs) have been extensively studied and found to have unique biological activity compared to CO gas. These CORMs show CO-independent biological activity and release CO in different ways. This review critically summarizes literature findings on CORMs and aims to provide essential criteria for an appropriate donor for studying CO biology.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Immunology
Sebastien Fauteux-Daniel, Laura Merlo M. Pich, Charlotte Girard-Guyonvarc'h, Assunta Caruso, Emiliana Rodriguez, Cem Gabay
Summary: This study investigates the expression and function of IL-18 and IL-18BP in K/BxN serum transfer arthritis (STA) model. The results show that IL-18 and IL-18BP mRNA levels are increased in arthritic joints, but the IL-18/IL-18BP balance is not involved in the regulation of STA.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Chemistry, Analytical
Dongning Liu, Xiaoxiao Yang, Binghe Wang
Summary: It is important to use reliable sources of CO and verify their ability to detect CO when developing CO probes.
ANALYTICAL CHEMISTRY
(2023)
Article
Immunology
Mercedes Lopez-Santalla, Carmen Conde, Angela Rodriguez-Trillo, Marina Garin
Summary: Rheumatoid arthritis is an autoimmune disease with unresolved treatment issues. Mesenchymal stem cell therapy has emerged as a potential alternative, but its effectiveness may vary in different arthritis models.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Nurul Ajilah Mohamed Khir, Ain' Sabreena Mohd Noh, Idris Long, Rahimah Zakaria, Che Aishah Nazariah Ismail
Summary: The role of carbon monoxide (CO) in regulating neurotransmitters and neuropeptides in the nervous system is still controversial. Exogenous CO gas inhalation has shown protective effects against pathological conditions, but its therapeutic use is limited due to the generation of toxic carboxyhaemoglobin. To overcome this limitation, a controlled-release CO molecule called CORM-2 has been developed. This review focuses on the potential mechanisms of CORM-2 in reducing pain, particularly in chronic and neuropathic pain.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2023)
Article
Immunology
Thomas Weissmann, Michael Rueckert, Jian-Guo Zhou, Michaela Seeling, Sebastian Lettmaier, Anna-Jasmina Donaubauer, Falk Nimmerjahn, Oliver J. Ott, Markus Hecht, Florian Putz, Rainer Fietkau, Benjamin Frey, Udo S. Gaipl, Lisa Deloch
Summary: Osteoarthritis is a common degenerative joint disease, particularly affecting the ankle and foot. Low-dose radiotherapy has been shown to be highly effective in treating osteoarthritis, with analgesic effects mediated by an interplay of cellular and immune factors, especially in younger patients.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Nicola Bauer, Xiaoxiao Yang, Zhengnan Yuan, Binghe Wang
Summary: CO is an endogenous signaling molecule that can modulate immune responses and engage circadian clock components. CORM-A1, one of the commonly used CO-release molecules, shows variable CO release efficiency and rate depending on factors such as the medium used and redox environment. The significant chemical reactivity of CORM-A1 suggests caution in using it as a CO surrogate in biological studies.
Article
Pharmacology & Pharmacy
Jing Tang, Xiaolan Cheng, Shiyu Yi, Yuanyuan Zhang, Zhigang Tang, Yutong Zhong, Qiuping Zhang, Bin Pan, Yubin Luo
Summary: This study investigated the therapeutic effect of the diterpenoid EFL2 derived from Euphorbia seeds on rheumatoid arthritis and explored its potential anti-arthritic mechanisms. The results demonstrated that EFL2 effectively reduced inflammation and interfered with the TLR7-mediated signaling pathway, providing a potential treatment option for rheumatoid arthritis.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Hannah M. Southam, Michael P. Williamson, Jonathan A. Chapman, Rhiannon L. Lyon, Clare R. Trevitt, Peter J. F. Henderson, Robert K. Poole
Summary: CORMs are molecules used to release carbon monoxide, showing antibacterial activity while being benign to mammalian cells. CORM-2 exhibits potent antibacterial activity, possibly linked to ruthenium toxicity, and exogenous amino acids and thiols can protect bacteria from the effects of CORM-2.
Article
Chemistry, Physical
Xiao Zhang, Nan Guo, Shuhong Yang, Huma Khan, Weiqiang Zhang
Summary: The poor water solubility and instability of Ru(II) carbonyl complex restrict its use as CO-releasing materials (CO-RMs) for therapeutic applications. In this study, a robust Ru(I) carbonyl sawhorse skeleton was modified with a water-soluble PEGylated sidearm to enhance the hydrophilicity and bioactivity of CO. The results showed that both the bridging carboxylate ligands and PEGylated axial ligands regulate the hydrophilicity of the CO-RMs. CO-RM 4-13 exhibited sustained release of therapeutic amounts of CO under photolysis conditions. The more hydrophilic CO-RMs released CO at a faster rate, as demonstrated by the correlation between CO release kinetics and hydrophilicity. Additionally, the low cytotoxic CO-RM 4 displayed specific anticancer activity against HT-29 tumor cells.
Article
Biochemistry & Molecular Biology
Emrah Ipek, Gamze Sevri Ekren Asici, Busra Kibar Kurt, Erkmen Tugrul Epikmen, Sule Yurdagul Ozsoy, Recai Tunca
Summary: The effect of low-dose carbon monoxide (CO) administration on peritoneal adhesion (PA) formation was investigated. The results showed that CO administration reduced PA formation by affecting adhesiogenic processes such as pro-inflammatory response, fibrinolytic system, angiogenesis, and fibrogenesis.
MOLECULAR BIOLOGY REPORTS
(2023)
Article
Immunology
Takafumi Obara, Hirotsugu Yamamoto, Toshiyuki Aokage, Takuro Igawa, Tsuyoshi Nojima, Takahiro Hirayama, Mizuki Seya, Michiko Ishikawa-Aoyama, Atsunori Nakao, Roberto Motterlini, Hiromichi Naito
Summary: The intraluminal administration of water-soluble CORM-3 during cold storage of intestinal grafts has been found to provide protective effects against ischemia/reperfusion injury. It improves graft blood flow, mucosal barrier function, as well as recipient survival rates.
Article
Spectroscopy
Yonggang Yang, Yang Liu, Kai Jiang, Yufang Liu
Summary: The theoretical study on the fluorescent detection mechanism of CORM3-green on CORM-3 reveals that the intermolecular hydrogen bonds hinder the intramolecular hydrogen bond and excited state intramolecular proton transfer of the keto form of PTI, leading to the experimental Stokes shift mainly caused by intermolecular hydrogen bonding rather than by ESIPT process. The proposed explanation provides insights into the detection mechanism of CORM3-green and experimental fluorescence phenomenon.
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
(2021)
Article
Chemistry, Medicinal
Emanuela Berrino, Laura Micheli, Simone Carradori, Lorenzo di Cesare Mannelli, Paolo Guglielmi, Alessandro De Luca, Fabrizio Carta, Carla Ghelardini, Daniela Secci, Claudiu T. Supuran
Summary: Pain control is crucial in rheumatoid arthritis (RA) patients, but current treatments have limited effectiveness and risk of side effects. In this study, we proposed a novel approach combining carbonic anhydrase inhibitors (CAIs) with CO releasing molecules (CORMs). The resulting CAI-CORM hybrids showed significant anti-inflammatory effects and pain relief in RA rat models. Our findings demonstrate the potential of CAI-CORM hybrids as anti-nociceptive agents against arthritis.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Emanuela Berrino, Laura Micheli, Simone Carradori, Lorenzo di Cesare Mannelli, Paolo Guglielmi, Alessandro De Luca, Fabrizio Carta, Carla Ghelardini, Daniela Secci, Claudiu T. Supuran
Summary: This study proposes a novel approach to relieve pain in patients with rheumatoid arthritis by combining carbonic anhydrase inhibitors (CAIs) and CO releasing molecules (CORMs). The resulting CAI-CORM hybrids exhibit strong anti-inflammatory effects in in vitro disease models and relieve pain symptoms in an in vivo RA rat model.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Zeina El Ali, Anthony Ollivier, Sylvie Manin, Michael Rivard, Roberto Motterlini, Roberta Foresti
Article
Endocrinology & Metabolism
Camille Sollier, Emilie Capel, Caroline Aguilhon, Vasily Smirnov, Martine Auclair, Claire Douillard, Miriam Ladsous, Sabine Defoort-Dhellemmes, Jennifer Gorwood, Laura Braud, Roberto Motterlini, Camille Vatier, Olivier Lascols, Eric Renard, Corinne Vigouroux, Isabelle Jeru
Summary: Biallelic LIPE null variants were identified in three unrelated patients with Multiple Symmetric Lipomatosis (MSL) and/or partial lipodystrophy, leading to a multisystemic disease with various metabolic and neurological complications. Loss of HSL expression impairs adipocyte differentiation, consistent with the lipodystrophy/MSL phenotype and associated metabolic complications, indicating the importance of detailed ophthalmological examination for retinal damage in these patients.
EUROPEAN JOURNAL OF ENDOCRINOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Laura Braud, Maria Pini, Donald F. Stec, Sylvie Manin, Genevieve Derumeaux, David E. Stec, Roberta Foresti, Roberto Motterlini
Summary: The up-regulation of Sirt1 levels specifically in the visceral adipose tissue of Nrf2(-/-) mice is a key adaptive mechanism that mitigates glucose intolerance induced by nutritional stress.
Article
Biology
Qiyue Mao, Akira T. Kawaguchi, Shun Mizobata, Roberto Motterlini, Roberta Foresti, Hiroaki Kitagishi
Summary: Mao et al. reported a highly sensitive quantification of carbon monoxide using a simple colorimetric assay with the synthetic supramolecular compound hemoCD1. This method can detect CO distribution in organs, including the brain, and can also function as a CO scavenger to eliminate residual CO accumulated in organs. The authors also demonstrated the protective role of circulating hemoglobin in CO intoxication.
COMMUNICATIONS BIOLOGY
(2021)
Article
Cell Biology
Maria Pini, Gabor Czibik, Daigo Sawaki, Zaineb Mezdari, Laura Braud, Thais Delmont, Raquel Mercedes, Cecile Martel, Nelly Buron, Genevieve Marcelin, Annie Borgne-Sanchez, Roberta Foresti, Roberto Motterlini, Corneliu Henegar, Genevieve Derumeaux
Summary: White adipose tissue (WAT) cellular senescence increases early after initiation of high-fat diet, leading to changes in energy metabolism. Daily exercise reverses cellular senescence without weight and fat loss, reducing glycolysis and ATP production.
Article
Cardiac & Cardiovascular Systems
Javaid Iqbal, Janet Chamberlain, Mabruka Alfaidi, Matthew Hughes, Tooba Alizadeh, Helen Casbolt, Paul Evans, Brian Mann, Roberto Motterlini, Sheila Francis, Julian Gunn
Summary: The study shows that the use of CORM-A1 can significantly reduce infarct size in a pig model, improve cardiac function, and show no evidence of liver or kidney toxicity. The cardioprotective effects of CORM-A1 may be associated with reduced cell proliferation and inflammation.
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
(2021)
Article
Physics, Applied
Claire Douat, Pablo Escot Bocanegra, Sebastien Dozias, Eric Robert, Roberto Motterlini
Summary: This study introduces a new method for delivering carbon monoxide using a helium plasma jet with a CO2 admixture, showing potential therapeutic applications and the ability to tune CO production. It also reveals for the first time that plasma can generate and deliver CO for therapeutic interventions.
PLASMA PROCESSES AND POLYMERS
(2021)
Article
Biology
Laura Le Pelletier, Matthieu Mantecon, Jennifer Gorwood, Martine Auclair, Roberta Foresti, Roberto Motterlini, Mireille Laforge, Michael Atlan, Bruno Feve, Jacqueline Capeau, Claire Lagathu, Veronique Bereziat
Summary: As individuals age, adipose-derived stromal cells (ASCs) exhibit distinct characteristics, with in vitro aging experiments showing the presence of senescence and oxidative stress.
Article
Immunology
Takafumi Obara, Hirotsugu Yamamoto, Toshiyuki Aokage, Takuro Igawa, Tsuyoshi Nojima, Takahiro Hirayama, Mizuki Seya, Michiko Ishikawa-Aoyama, Atsunori Nakao, Roberto Motterlini, Hiromichi Naito
Summary: The intraluminal administration of water-soluble CORM-3 during cold storage of intestinal grafts has been found to provide protective effects against ischemia/reperfusion injury. It improves graft blood flow, mucosal barrier function, as well as recipient survival rates.
Article
Biochemistry & Molecular Biology
Pooja Pradhan, Vijith Vijayan, Karsten Cirksena, Falk F. R. Buettner, Kazuhiko Igarashi, Roberto Motterlini, Roberta Foresti, Stephan Immenschuh
Summary: In this study, the role of BACH1 in mouse macrophages was investigated using a proteomics approach. The results showed that genetic deletion of BACH1 led to reduced levels of mitochondrial proteins, altered mitochondrial energy metabolism, and increased activation of the NLRP3 inflammasome. This study highlights the critical role of BACH1 in modulating macrophage immune responses.
Article
Biochemistry & Molecular Biology
Grazia Scandura, Cesarina Giallongo, Fabrizio Puglisi, Alessandra Romano, Nunziatina Laura Parrinello, Tatiana Zuppelli, Lucia Longhitano, Sebastiano Giallongo, Michelino Di Rosa, Giuseppe Musumeci, Roberto Motterlini, Roberta Foresti, Giuseppe Alberto Palumbo, Giovanni Li Volti, Francesco Di Raimondo, Daniele Tibullo
Summary: In this study, the mechanisms of chemoresistance in multiple myeloma (MM) relapse were investigated. The researchers found that heme oxygenase-1 (HO-1) and Toll-like receptor 4 (TLR4) protected MM cells from the proteasome inhibitor bortezomib (BTZ). Inhibition of HO-1 and TLR4 increased cell toxicity and mitochondrial depolarization by BTZ. Furthermore, the combination of TLR4 inhibition and BTZ treatment activated mitophagy and decreased the unfolded protein response (UPR) survival pathway by downregulating HO-1 expression.
Article
Cell Biology
Kenza Ngono Ayissi, Jennifer Gorwood, Laura Le Pelletier, Christine Bourgeois, Carine Beaupere, Martine Auclair, Roberta Foresti, Roberto Motterlini, Michael Atlan, Aurelie Barrail-Tran, Roger Le Grand, Delphine Desjardins, Bruno Feve, Olivier Lambotte, Jacqueline Capeau, Veronique Bereziat, Claire Lagathu
Summary: Treatment with integrase-strand-transfer-inhibitors (INSTIs) can lead to adipose tissue gain and fibrosis, inhibiting beiging in adipose tissue and resulting in obesity and insulin resistance.
Article
Pharmacology & Pharmacy
Shruti Mohan, Louis -Antoine Barel, Djamal Eddine Benrahla, Bernard Do, Qiyue Mao, Hiroaki Kitagishi, Michael Rivard, Roberto Motterlini, Roberta Foresti
Summary: It has been discovered that metal carbonyls can be grafted onto polysaccharides to efficiently deliver carbon monoxide to cells, especially adipocytes. Oral administration of two functionalized CO-RMs glyco-CORMs (5b and 6b) can lead to CO accumulation in multiple organs, including adipose tissue. Furthermore, glyco-CORM 6b administered for eight weeks in mice fed a high-fat diet can result in anti-obesity and positive metabolic effects.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Multidisciplinary Sciences
Qiyue Mao, Xuansu Zhao, Akiko Kiriyama, Shigeru Negi, Yasutaka Fukuda, Hideki Yoshioka, Akira T. Kawaguchi, Roberto Motterlini, Roberta Foresti, Hiroaki Kitagishi
Summary: In this study, an injectable antidote against simultaneous poisoning by carbon monoxide (CO) and hydrogen cyanide (CN-) was invented. The antidote showed remarkable protective effects in mouse and rat models, improving survival rates and reducing CO and CN- levels in the blood. Pharmacokinetic data demonstrated fast urinary excretion and short elimination half-life of the antidote. Furthermore, the antidote was effective in improving survival and promoting rapid recovery from physical incapacitation in a simulated fire accident scenario.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Cell Biology
Nioosha Nekooie Marnany, Redouane Fodil, Sophie Fereol, Alwyn Dady, Marine Depp, Frederic Relaix, Roberto Motterlini, Roberta Foresti, Jean-Loup Duband, Sylvie Dufour
Summary: Glucose metabolism plays a crucial role in the development of avian trunk neural crest cells (NCCs). Trunk NCCs prefer glucose oxidation, while cranial NCCs rely on aerobic glycolysis. Multiple pathways, including glycolysis, mitochondrial respiration, and the pentose phosphate pathway, are mobilized and integrated for the coordinated execution of diverse cellular programs in trunk NCCs.
JOURNAL OF CELL SCIENCE
(2023)