Acetaldehyde cytotoxicity in cultured rat astrocytes

Hołownia, Adam; Ledig, M.; Braszko, Jan J.; Ménez, J. F.

doi:10.1016/s0006-8993(99)01529-2

Cited by 44 publications

(32 citation statements)

References 40 publications

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“…In cells in the hepatic system, it has been shown that ethanol as well as acetaldehyde can alter the cytokine signaling pathway and induction process [7,12]. Although acetaldehyde was shown to increase intracellular calcium levels, DNA fragmentation and transglutaminase activity in astrocytes [10], results from the present study indicate no apparent effects of acetaldehyde on the cytokine induction of NO.…”

Section: Discussioncontrasting

confidence: 74%

Ethanol inhibits cytokine-induced iNOS and sPLA2 in immortalized astrocytes: Evidence for posttranscriptional site of ethanol action

Wang

Sun

2001

J Biomed Sci

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Chronic and excessive ethanol consumption is known to alter neuron and glial cell functions in the central nervous system (CNS). Astrocytes comprise the major cell type in the brain. These immune active cells are capable of responding to proinflammatory cytokines and endotoxins, which stimulate transcriptional pathways leading to induction of genes, including the inducible nitric oxide synthase (iNOS) and secretory phospholipase A2 (sPLA2). In this study, we investigate the effects of ethanol on cytokine-induced iNOS and sPLA2 in immortalized astrocytes (DITNC). When DITNC cells were exposed to ethanol (0-200 mM) for 4 h prior to subsequent stimulation with cytokines for 16 h, NO production decreased with increasing ethanol concentrations starting from 50 mM. At ethanol concentrations higher than 100 mM, ethanol also inhibited cytokine-induced sPLA2 release into the culture medium. The inhibitory effect of ethanol on NO production corresponds well with the decrease in iNOS protein and NOS enzyme activity, but not with iNOS and sPLA2 mRNA nor binding of NF-kappaB to DNA. The inhibition of cytokine-induced NO production by ethanol was also dependent on the time of ethanol exposure to the cells, but addition of acetaldehyde up to 200 microM did not elicit any changes. Taken together, these results provide evidence for a posttranscriptional mode of ethanol action on the cytokine induction pathway for NO production in astrocytes.

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Section: Discussioncontrasting

confidence: 74%

Ethanol inhibits cytokine-induced iNOS and sPLA2 in immortalized astrocytes: Evidence for posttranscriptional site of ethanol action

Wang

Sun

2001

J Biomed Sci

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“…However, there are only a few data about the cytotoxicity of acetaldehyde in astrocytes. Acetaldehyde, but not ethanol, increases intracellular calcium level, elevates transglutaminase activity, and causes signifi cant DNA fragmentation and cell nuclei chromatin condensation in astrocytes (50). We have shown that pretreatment with catalase inhibitor AMT signifi cantly diminishes ethanol toxicity (28 % lower after 24 hours of exposure and 24.1 % lower after seven days of exposure).…”

Section: Discussionmentioning

confidence: 75%

“…After seven days of exposure, acetaldehyde inhibited cell growth at much lower concentrations than ethanol; the fi rst signifi cant decrease in cell number was observed at 5 mmol L -1 acetaldehyde ( Figure 3B). EC 50 Figure 3D). …”

Section: The Effect Of Ethanol and Acetaldehyde On Cell Proliferationmentioning

confidence: 98%

Comparison of Ethanol and Acetaldehyde Toxicity in Rat Astrocytes in Primary Culture

Šarc

Lipnik‐Štangelj²

2009

Archives of Industrial Hygiene and Toxicology

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This study compared the effects of toxicity of ethanol and its fi rst metabolite acetaldehyde in rat astrocytes through cell viability and cell proliferation. The cells were treated with different concentrations of ethanol in the presence or absence of a catalase inhibitor 2-amino-1,2,4 triazole (AMT) or with different concentrations of acetaldehyde. Cell viability was assessed using the trypan blue test. Cell proliferation was assessed after 24 hours and after seven days of exposure to either ethanol or acetaldehyde. We showed that both ethanol and acetaldehyde decreased cell viability in a dose-dependent manner. In proliferation studies, after seven days of exposure to either ethanol or acetaldehyde, we observed a signifi cant dose-dependent decrease in cell number. The protein content study showed biphasic dose-response curves, after 24 hours and seven days of exposure to either ethanol or acetaldehyde. Co-incubation in the presence of AMT signifi cantly reduced the inhibitory effect of ethanol on cell proliferation. We concluded that long-term exposure of astrocytes to ethanol is more toxic than acute exposure. Acetaldehyde is a much more potent toxin than ethanol, and at least a part of ethanol toxicity is due to ethanol's fi rst metabolite acetaldehyde.

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“…6) and because free aldehyde changes membrane stability and may promote calcium influx associated with cell apoptosis (43,44), in vitro calcium concentration was monitored by using the cell-permeable dye, Fluo-3 AM. All-transretinal and calcium ionophore A23187 increased the fluorescent intensity of cells loaded with Fluo-3, indicating an increased intracellular calcium concentration, whereas alltrans-retinol, rapidly produced from all-trans-retinal in the eye, had no significant effect (Fig.…”

Section: ϫ2mentioning

confidence: 99%

Involvement of All-trans-retinal in Acute Light-induced Retinopathy of Mice

Maeda¹,

Maeda²,

Golczak³

et al. 2009

Journal of Biological Chemistry

220

307

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Exposure to bright light can cause visual dysfunction and retinal photoreceptor damage in humans and experimental animals, but the mechanism(s) remain unclear. We investigated whether the retinoid cycle (i.e. the series of biochemical reactions required for vision through continuous generation of 11-cis-retinal and clearance of all-trans-retinal, respectively) might be involved. Previously, we reported that mice lacking two enzymes responsible for clearing all-trans-retinal, namely photoreceptor-specific ABCA4 (ATP-binding cassette transporter 4) and RDH8 (retinol dehydrogenase 8), manifested retinal abnormalities exacerbated by light and associated with accumulation of diretinoid-pyridinium-ethanolamine (A2E), a condensation product of all-trans-retinal and a surrogate marker for toxic retinoids. Now we show that these mice develop an acute, light-induced retinopathy. However, cross-breeding these animals with lecithin:retinol acyltransferase knock-out mice lacking retinoids within the eye produced progeny that did not exhibit such light-induced retinopathy until gavaged with the artificial chromophore, 9-cis-retinal. No significant ocular accumulation of A2E occurred under these conditions. These results indicate that this acute light-induced retinopathy requires the presence of free all-trans-retinal and not, as generally believed, A2E or other retinoid condensation products. Evidence is presented that the mechanism of toxicity may include plasma membrane permeability and mitochondrial poisoning that lead to caspase activation and mitochondria-associated cell death. These findings further understanding of the mechanisms involved in light-induced retinal degeneration.

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Acetaldehyde cytotoxicity in cultured rat astrocytes

Cited by 44 publications

References 40 publications

Ethanol inhibits cytokine-induced iNOS and sPLA2 in immortalized astrocytes: Evidence for posttranscriptional site of ethanol action

Ethanol inhibits cytokine-induced iNOS and sPLA2 in immortalized astrocytes: Evidence for posttranscriptional site of ethanol action

Comparison of Ethanol and Acetaldehyde Toxicity in Rat Astrocytes in Primary Culture

Involvement of All-trans-retinal in Acute Light-induced Retinopathy of Mice

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