Differential metabolism of 4-hydroxynonenal in liver, lung and brain of mice and rats

Zheng, Ruijin; Mishin, Vladimir; Richardson, Jason R.; Heck, Diane E.; Laskin, Debra L.; Laskin, Jeffrey D.

doi:10.1016/j.taap.2014.04.026

Cited by 38 publications

(28 citation statements)

References 57 publications

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“…Li et al (2011a) observed in mouse pulmonary cytosol GST activity toward ethylene oxide as substrate. Zheng et al (2014) observed that GST specific activity toward the prototypic substrate 4-hydroxynonenal was very high in mouse lung 9000 g supernatant, almost as high as in the liver.…”

Section: Enzymatic Activitymentioning

confidence: 95%

Xenobiotica-metabolizing enzymes in the lung of experimental animals, man and in human lung models

2019

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The xenobiotic metabolism in the lung, an organ of first entry of xenobiotics into the organism, is crucial for inhaled compounds entering this organ intentionally (e.g. drugs) and unintentionally (e.g. work place and environmental compounds). Additionally, local metabolism by enzymes preferentially or exclusively occurring in the lung is important for favorable or toxic effects of xenobiotics entering the organism also by routes other than by inhalation. The data collected in this review show that generally activities of cytochromes P450 are low in the lung of all investigated species and in vitro models. Other oxidoreductases may turn out to be more important, but are largely not investigated. Phase II enzymes are generally much higher with the exception of UGT glucuronosyltransferases which are generally very low. Insofar as data are available the xenobiotic metabolism in the lung of monkeys comes closed to that in the human lung; however, very few data are available for this comparison. Second best rate the mouse and rat lung, followed by the rabbit. Of the human in vitro model primary cells in culture, such as alveolar macrophages and alveolar type II cells as well as the A549 cell line appear quite acceptable. However, (1) this generalization represents a temporary oversimplification born from the lack of more comparable data; (2) the relative suitability of individual species/models is different for different enzymes; (3) when more data become available, the conclusions derived from these comparisons quite possibly may change.

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Section: Enzymatic Activitymentioning

confidence: 95%

Xenobiotica-metabolizing enzymes in the lung of experimental animals, man and in human lung models

2019

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“…Consistently Zheng et al also found that lung and brain in rat and mouse showed limited activity of HNE degradation by alcohol/aldehyde dehydrogenase compared to liver [28]. In addition, GST expression level and activity also vary with tissues [28]. Such variation in HNE metabolizing activity in different tissues means that HNE concentration may vary from tissue to tissue in vivo.…”

Section: Tissue Concentration Of Hnementioning

confidence: 78%

“…The last had less than 3% of the HNE metabolizing activity of liver, largely due to the lack of alcohol/aldehyde dehydrogenase activity in these tissues [25]. Consistently Zheng et al also found that lung and brain in rat and mouse showed limited activity of HNE degradation by alcohol/aldehyde dehydrogenase compared to liver [28]. In addition, GST expression level and activity also vary with tissues [28].…”

Section: Tissue Concentration Of Hnementioning

confidence: 98%

“…HNE biotransformation in the other pathways leads to its oxidation to 4-hydroxy-2-nonenoic acid (HNA) by aldehyde dehydrogenase [25, 26], or its reduction to 1, 4-dihydroxy-2-nonene (DHN) by alcohol dehydrogenase [25] and aldo-keto reductase [27]. With reduction, HNE loses its ability to conjugate with proteins [28]. But even though the metabolic removal of HNE is efficient, 2-8% of the HNE in cells appears to form conjugates with proteins [18], and initiates signaling events.…”

Section: Tissue Concentration Of Hnementioning

confidence: 99%

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Signaling by 4-hydroxy-2-nonenal: Exposure protocols, target selectivity and degradation

Zhang

2017

Archives of Biochemistry and Biophysics

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4-hydroxy-2-nonenal (HNE), a major non-saturated aldehyde product of lipid peroxidation, has been extensively studied as a signaling messenger. In these studies a wide range of HNE concentrations have been used, ranging from the unstressed plasma concentration to far beyond what would be found in actual pathophysiological condition. In addition, accumulating evidence suggest that signaling protein modification by HNE is specific with only those proteins with cysteine, histidine, and lysine residues located in certain sequence or environments adducted by HNE. HNE-signaling is further regulated through the turnover of HNE-signaling protein adducts through proteolytic process that involve proteasomes, lysosomes and autophagy. This review discusses the HNE concentrations and exposure modes used in signaling studies, the selectivity of the HNE-adduction site, and the turnover of signaling protein adducts.

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“…Medicinal plants and bioactive compounds are found to enhance metabolism, detoxification or clearance of 4-HNE by regulating activities of endogenous enzymes (such as AR, GST, and AKRs), which may provide the effective strategies for combating 4-HNE-driven deleterious effects. Because of differential metabolisms of 4-HNE observed in liver, lung, and brain of rodents [130], further study is warranted to determine whether these medicinal plants and bioactive compounds have the capacity to mediate oxidative, reductive, and conjugative pathways to metabolize 4-HNE and 4-HNE adducts in oxidative stress-triggered injury of these tissues.…”

Section: The Strategy For Developing Potential Therapymentioning

confidence: 99%

Can Medicinal Plants and Bioactive Compounds Combat Lipid Peroxidation Product 4-HNE-Induced Deleterious Effects?

Wang

et al. 2020

Biomolecules

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The toxic reactive aldehyde 4-hydroxynonenal (4-HNE) belongs to the advanced lipid peroxidation end products. Accumulation of 4-HNE and formation of 4-HNE adducts induced by redox imbalance participate in several cytotoxic processes, which contribute to the pathogenesis and progression of oxidative stress-related human disorders. Medicinal plants and bioactive natural compounds are suggested to be attractive sources of potential agents to mitigate oxidative stress, but little is known about the therapeutic potentials especially on combating 4-HNE-induced deleterious effects. Of note, some investigations clarify the attenuation of medicinal plants and bioactive compounds on 4-HNE-induced disturbances, but strong evidence is needed that these plants and compounds serve as potent agents in the prevention and treatment of disorders driven by 4-HNE. Therefore, this review highlights the pharmacological basis of these medicinal plants and bioactive compounds to combat 4-HNE-induced deleterious effects in oxidative stress-related disorders, such as neurotoxicity and neurological disorder, eye damage, cardiovascular injury, liver injury, and energy metabolism disorder. In addition, this review briefly discusses with special attention to the strategies for developing potential therapies by future applications of these medicinal plants and bioactive compounds, which will help biological and pharmacological scientists to explore the new vistas of medicinal plants in combating 4-HNE-induced deleterious effects.

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Differential metabolism of 4-hydroxynonenal in liver, lung and brain of mice and rats

Cited by 38 publications

References 57 publications

Xenobiotica-metabolizing enzymes in the lung of experimental animals, man and in human lung models

Xenobiotica-metabolizing enzymes in the lung of experimental animals, man and in human lung models

Signaling by 4-hydroxy-2-nonenal: Exposure protocols, target selectivity and degradation

Can Medicinal Plants and Bioactive Compounds Combat Lipid Peroxidation Product 4-HNE-Induced Deleterious Effects?

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