Mechanism of inhibitory action of ethanol on inducible nitric oxide synthesis in macrophages

Wakabayashi, Ichiro; Negoro, Munetaka

doi:10.1007/s00210-002-0625-z

Cited by 14 publications

(6 citation statements)

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“…Ethanol and methanol showed harmless effects on MDA-MB-231, MCF-7 and VNBRCA1 even at the high concentration of up to 2%. Similarly, though not using the same cell lines as in our study, a previous study also found that 2.8% ethanol did not affect the cell viability of RAW 264.7 8 . In another report studying the effects of ethanol on HeLa cells, it was found that 5% ethanol (or higher concentrations) compromised cell viability 9 .…”

Section: Discussionsupporting

confidence: 42%

Comparative cytotoxic effects of methanol, ethanol and DMSO on human cancer cell lines

2020

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Introduction: Anti-tumor drug screening is the most popular technique in drug discovery. In this technique, various agents were tested for their cytotoxicity on cell lines, particularly cancer cell lines. Since most of these agents are weakly soluble in water, they can be normally dissolved in lipophilic solvents. To obtain accurate results, the requirement of these solvents are that they be biocompatible and non-toxic to cells. The aim of this study was to investigate the biological effects of the three agents most commonly used as drug vehicles, i.e. dimethyl sulfoxide (DMSO), ethanol and methanol, using cell proliferation measurement techniques. Methods: To minimize the errors from the measurement techniques, this study used the xCelligence RTCA system which entails real-time monitoring of cell proliferation without dye labeling. Under the wide range concentration of solvents (from 0% to 100% of solvents by serial dilutions), the cell index (CI) and slope of cell proliferation curves of HepG2, MDA-MB-231, MCF-7 and VNBRCA1 cell lines were analyzed (by the software provided by the xCelligence system). Results: The results showed that DMSO had a significant toxicity and inhibition of proliferation on 4 cell lines, at the concentrations of 10%, 5%, 2.5% and 1.25% (p<0.0001). Methanol and ethanol inhibited cellular proliferation at the concentrations of 10% and 5% (p<0.0001). The concentrations of ethanol and methanol ranging from 2.5% to 0.15% concentration were well-tolerated by cells with respect to proliferation. Depending on the extracts or agents, each should be diluted in the suitable vehicle at the proper concentrations. Conclusion: Ethanol and methanol are good choices for solvents since they have low toxicity on HepG2, MDA-MB-231, MCF-7 and VNBRCA1 cell lines. However, in the case of agents only dissolvable in DMSO, low concentrations of DMSO from 0.6%-0.015% should be considered.

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Section: Discussionsupporting

confidence: 42%

Comparative cytotoxic effects of methanol, ethanol and DMSO on human cancer cell lines

2020

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“…NOS inhibitor attenuated and NOS donor stimulated the apoptosis, which seems to be mediated through the generation of NO [46]. However acute EtOH inhibits the lipopolysaccharide (LPS)-induced NO response in Kupffer, hepatic endothelial cells [47], and macrophages [48,49]. Similarly acute EtOH exposure enhanced cytokine-induced iNOS expression at a pretranslational site in astroglial cells [50].…”

Section: Effect Of Etoh On Nosmentioning

confidence: 99%

“…Both acute (24 h, 150 mM) and chronic (10 days, 30 mM) EtOH exposure suppressed iNOS induction by co-administration of phorbol 12-myristate 13-acetate (PMA) and LPS in brain glial cells [46,52]. The inhibitory effects of EtOH on iNOS mRNA is not due to the metabolism of EtOH to acetaldehyde and acetate [50,53] but due to inhibiting nuclear transcription factor-kappaB (NFkappaB) [48] and inhibiting signal transducer and activator of transcription-1 (STAT-1) activation [49]. Furthermore, different doses of EtOH affected iNOS expression in glial cells.…”

Section: Effect Of Etoh On Nosmentioning

confidence: 99%

Ethanol Metabolism and Effects: Nitric Oxide and its Interaction

Deng

Deitrich²

2007

CCP

110

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Ethanol (EtOH) in alcoholic beverages is consumed by a large number of individuals and its elimination is primarily by oxidation. The role of nitric oxide (NO) in EtOH's effects is important since NO is one of the most prominent biological factors in mammals. NO is constantly formed endogenously from L-arginine. Dose and length of EtOH exposure, and cell type are the main factors affecting EtOH effects on NO production. Either acute or chronic EtOH ingestion affects inducible NO synthase (iNOS) activity. However it seems that EtOH suppresses induced-NO production by inhibition of iNOS in different cells. On the other hand, it is clear that acute low doses of EtOH increase both the release of NO and endothelial NOS (eNOS) expression, and augment endothelium-mediated vasodilatation, whereas higher doses impair endothelial functions. EtOH selectively affects neuronal NOS (nNOS) activity in different brain cells, which may relate to various behavioral interactions. Therefore, there is an excellent chance for EtOH and NO to react with each other. Effects of EtOH on NO production and NOS activity may be important to EtOH modification of cell or organ function. Nitrosated compounds (alkyl nitrites) are often found as the interaction products, which might be one of the minor pathways of EtOH metabolism. NO also inhibits EtOH metabolizing enzymes. Furthermore, NO is involved in EtOH induced liver damage and has a role in fetal development during EtOH exposure in pregnancy. The mechanisms underlying these effects are only partially understood. Hence, the current discussion of the interaction of EtOH and NO is presented.

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“…In inflammatory contexts, there is increase in the secretion of soluble mediators such as pro-inflammatory cytokines, including TNF-a, IL-1, IL-6 and IL-8. Activation of macrophage by pro-inflammatory cytokines is an efficient pathway to activate iNOS leading to higher synthesis of nitric oxide (NO) directly involved in macrophage bactericidal activity and efficient phagocytosis [1,3].…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, most reports have focussed on early alterations induced by EtOH consumption or those observed following direct in vitro addition of EtOH over macrophages and lymphocyte cultures [4][5][6][7]. The immunological alterations already reported following EtOH administration describe mainly the suppression of inflammatory-type cytokines, including reduced levels IL-2 and IFN-c [8,9], impairment of TNF-a, IL-1 and IL-6 production by human macrophages and murine Kupffer cells [10][11][12], and inhibition of iNOS induction at the transcriptional level in macrophage [3].…”

Section: Introductionmentioning

confidence: 99%

The Long‐term Impaired Macrophages Functions are Already Observed Early after High‐dose Ethanol Administration

et al. 2008

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Herein, we described an experimental model of high‐dose ethanol (EtOH) administration, able to induce in vitro impairment in macrophage phagocytic capacity, already observed at 24 h after the last EtOH administration. This phenomenon was characterized by enlarged time required for adhesion and internalization events. Parallel studies documented an overall impaired production of interleukin (IL)‐6 and nitric oxide (NO) production by peritoneal macrophages in EtOH‐treated mice following interferon (IFN)‐γ and lipopolysaccharide (LPS) stimuli. Although the impaired IL‐6 response could not be restored by any of the experimental conditions tested, the lower NO response to INF‐γ and LPS was overturned by simultaneous IFN‐γ/LPS stimuli. It was interesting to notice that high‐dose EtOH administration drives peritoneal macrophages towards long‐term impairment in phagocytosis capacity with slower adhesion time, but with no impact on the time required for internalization. Moreover, 30 days after the last EtOH administration, lower IL‐6 response to INF‐γ and impaired NO production were still observed in response to IFN‐γ/LPS stimuli, with the IL‐6 response to IFN‐γ being restored by IFN‐γ/LPS stimuli. Histological studies showed that high‐dose EtOH administration led to long‐term in vivo impairment of antigen‐clearance following OVA‐driven delayed‐type‐hypersensitivity induction, characterized by the presence of a large amount of unprocessed OVA surrounded by dermal inflammatory infiltrate, suggesting defective activity of antigen‐presenting cells. Together, these findings supported our hypothesis that the poor antigen clearance in vivo may be related to the impaired macrophage function in vitro. These observations in the murine experimental model may reflect some of the consequences of EtOH consumption by humans.

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Mechanism of inhibitory action of ethanol on inducible nitric oxide synthesis in macrophages

Cited by 14 publications

References 0 publications

Comparative cytotoxic effects of methanol, ethanol and DMSO on human cancer cell lines

Comparative cytotoxic effects of methanol, ethanol and DMSO on human cancer cell lines

Ethanol Metabolism and Effects: Nitric Oxide and its Interaction

The Long‐term Impaired Macrophages Functions are Already Observed Early after High‐dose Ethanol Administration

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