Natural Products that Generate Carbon Monoxide

and, Ladie Kimberly La Cruz; Wang, Binghe

doi:10.1002/9781119783435.ch17

Cited by 4 publications

(11 citation statements)

References 109 publications

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“…There is a small portion of CO that comes from the metabolism of heme sourced from other hemoproteins such as cytochrome P450. There is also the possibility of CO coming from the gut microbiome . CO largely exists in the form of COHb at varying levels under normal physiological conditions.…”

Section: An Overview Of Co’s Safety Profilesmentioning

confidence: 99%

“…In this review, we analyze CO’s safety profiles from 10 areas. First , CO is produced endogenously as part of a normal physiological process in red blood cell turnover as described earlier . There is a small portion of CO that comes from the metabolism of heme sourced from other hemoproteins such as cytochrome P450.…”

Section: An Overview Of Co’s Safety Profilesmentioning

confidence: 99%

“…CO largely exists in the form of COHb. The presence of up to 2% COHb is considered physiological, corresponding to about 150 μM when calculated using the average hemoglobin level of 7.5 mM . This means that under normal physiological conditions CO is largely stored in a hemoglobin “reservoir” as COHb.…”

Section: Endogenous Production Of Comentioning

confidence: 99%

“…The daily “average production” of CO is about 400 μmol per person, leading to the formation of CO-bound hemoglobin, known as COHb. As a result, 2% COHb is considered physiological . Given hemoglobin’s concentration of about 7.5 mM, 2% COHb corresponds to about 150 μM, which is higher than or comparable to the peak concentrations of many commonly used medications.…”

Section: Introductionmentioning

confidence: 99%

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Carbon Monoxide as a Potential Therapeutic Agent: A Molecular Analysis of Its Safety Profiles

Bansal,

Liu,

Mao

et al. 2024

J. Med. Chem.

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Section: An Overview Of Co’s Safety Profilesmentioning

confidence: 99%

Section: An Overview Of Co’s Safety Profilesmentioning

confidence: 99%

Section: Endogenous Production Of Comentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Carbon Monoxide as a Potential Therapeutic Agent: A Molecular Analysis of Its Safety Profiles

Bansal,

Liu,

Mao

et al. 2024

J. Med. Chem.

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“…It is important to note that under physiological conditions, CO can reach high micromolar concentrations in the hemoglobin-bound form, carboxyhemoglobin (COHb). 13 At high concentrations, CO toxicity is an issue with induction of Parkinsonism, cognitive impairment, loss of consciousness, or even death. The key is the level of exposure, as Paracelsus, commonly credited as the founder of modern toxicology, correctly stated about 500 years ago: "The dose makes the poison."…”

Section: Introductionmentioning

confidence: 99%

Unraveling the Interplay of Dopamine, Carbon Monoxide, and Heme Oxygenase in Neuromodulation and Cognition

Bauer,

Liu,

Nguyen

et al. 2024

ACS Chem. Neurosci.

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The dopaminergic system plays important roles in neuromodulation, including prominent roles in complex neurological functions such as cognition, reward, motivation, and memory. Understandably, the highly complex nature of such physiological functions means that their regulation is intertwined with other signaling pathways, as has been demonstrated by numerous studies. Contrary to its public perception of being poisonous at all concentrations, carbon monoxide (CO) is produced endogenously from heme degradation by heme oxygenase (HO) as part of the physiological process of red blood cell turnover. Physiological concentrations of CO can reach high micromolar ranges in the hemoglobin bound form. Low-dose CO has shown therapeutic effects in numerous animal models, including traumatic brain injury via engaging various hemoprotein targets. As such, the HO−CO axis has been shown to offer beneficial effects in organ protection, anti-inflammation, and neuroprotection, among many others. Further, a large number of publications have shown the interactions among CO, HO, and the dopaminergic system. In this review, we critically examine such experimental evidence in a holistic fashion and in the context of a possible dopamine−HO−CO signaling axis. We hope that this Perspective will stimulate additional investigations into the molecular connectivity related to this possible axis and open doors to the development of novel therapeutics that impact the dopaminergic system.

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On the Question of CO’s Ability to Induce HO-1 Expression in Cell Culture: A Comparative Study Using Different CO Sources

Yang,

Mao,

Wang

2024

ACS Chem. Biol.

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With the recognition of the endogenous signaling roles and pharmacological functions of carbon monoxide (CO), there is an increasing need to understand CO's mechanism of actions. Along this line, chemical donors have been introduced as CO surrogates for ease of delivery, dosage control, and sometimes the ability to target. Among all of the donors, two ruthenium− carbonyl complexes, CORM-2 and -3, are arguably the most commonly used tools for about 20 years in studying the mechanism of actions of CO. Largely based on data using these two CORMs, there has been a widely accepted inference that the upregulation of heme oxygenase-1 (HO-1) expression is one of the key mechanisms for CO's actions. However, recent years have seen reports of very pronounced chemical reactivities and CO-independent activities of these CORMs. We are interested in examining this question by conducting comparative studies using CO gas, CORM-2/-3, and organic CO donors in RAW264.7, HeLa, and HepG2 cell cultures. CORM-2 and CORM-3 treatment showed significant dose-dependent induction of HO-1 compared to "controls," while incubation for 6 h with 250−500 ppm CO gas did not increase the HO-1 protein expression and mRNA transcription level. A further increase of the CO concentration to 5% did not lead to HO-1 expression either. Additionally, we demonstrate that CORM-2/-3 releases minimal amounts of CO under the experimental conditions. These results indicate that the HO-1 induction effects of CORM-2/-3 are not attributable to CO. We also assessed two organic CO prodrugs, BW-CO-103 and BW-CO-111. BW-CO-111 but not BW-CO-103 dose-dependently increased HO-1 levels in RAW264.7 and HeLa cells. We subsequently studied the mechanism of induction with an Nrf2-luciferase reporter assay, showing that the HO-1 induction activity is likely due to the activation of Nrf2 by the CO donors. Overall, CO alone is unable to induce HO-1 or activate Nrf2 under various conditions in vitro. As such, there is no evidence to support attributing the HO-1 induction effect of the CO donors such as CORM-2/-3 and BW-CO-111 in cell culture to CO. This comparative study demonstrates the critical need to consider possible CO-independent effects of a chemical CO donor before attributing the observed biological effects to CO. It is also important to note that such in vitro results cannot be directly extrapolated to in vivo studies because of the increased level of complexity and the likelihood of secondary and/or synergistic effects in the latter.

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Natural Products that Generate Carbon Monoxide

Cited by 4 publications

References 109 publications

Carbon Monoxide as a Potential Therapeutic Agent: A Molecular Analysis of Its Safety Profiles

Carbon Monoxide as a Potential Therapeutic Agent: A Molecular Analysis of Its Safety Profiles

Unraveling the Interplay of Dopamine, Carbon Monoxide, and Heme Oxygenase in Neuromodulation and Cognition

On the Question of CO’s Ability to Induce HO-1 Expression in Cell Culture: A Comparative Study Using Different CO Sources

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