Cytotoxic and genotoxic effects of  -carotene breakdown products on primary rat hepatocytes

Alija, Avdulla

doi:10.1093/carcin/bgh056

Cited by 55 publications

(60 citation statements)

References 30 publications

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“…In the case with growth inhibition, the effect was more pronounced with oxidized lycopene than with the intact compound (Nara et al 2001). That autoxidation products can be more potent than the carotenoid itself have also been shown for ␤-carotene, where in vitro studies of genotoxicity for hepatocytes indicates that ␤-carotene has no effect, but an oxidation mixture does (Alija et al 2004). It is therefore conceivable that the cleavage products from autoxidized carotenoids catalyzed by BCO2 are, at least in part, responsible for the beneficial effects on health seen with a carotenoid-rich diet.…”

Section: Discussionmentioning

confidence: 82%

Cell Type-specific Expression of β-Carotene 9', 10'-Monooxygenase in Human Tissues

Lindqvist

Andersson

2005

J Histochem Cytochem.

116

100

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S U M M A R YThe symmetrically cleaving ␤ -carotene 15,15 Ј -monooxygenase (BCO1) catalyzes the first step in the conversion of provitamin A carotenoids to vitamin A in the mucosa of the small intestine. This enzyme is also expressed in epithelia in a variety of extraintestinal tissues. The newly discovered ␤ -carotene 9 Ј ,10 Ј -monooxygenase (BCO2) catalyzes asymmetric cleavage of carotenoids. To gain some insight into the physiological role of BCO2, we determined the expression pattern of BCO2 mRNA and protein in human tissues. By immunohistochemical analysis it was revealed that BCO2 was detected in cell types that are known to express BCO1, such as epithelial cells in the mucosa of small intestine and stomach, parenchymal cells in liver, Leydig and Sertoli cells in testis, kidney tubules, adrenal gland, exocrine pancreas, and retinal pigment epithelium and ciliary body pigment epithelia in the eye. BCO2 was uniquely detected in cardiac and skeletal muscle cells, prostate and endometrial connective tissue, and endocrine pancreas. The finding that the BCO2 enzyme was expressed in some tissues and cell types that are not sensitive to vitamin A deficiency and where no BCO1 has been detected suggests that BCO2 may also be involved in biological processes other than vitamin A synthesis. T he enzymatic action of ␤ -carotene 15,15 Ј -monooxygenases (BCO1) is crucial for the conversion of provitamin A carotenoids to retinol (vitamin A) in the epithelial cells of the small intestine mucosa. The enzyme cleaves the ␤ -ionone ring containing carotenoids centrally, which results in two aldehyde molecules with polyene chains of identical length. Thus cleavage of the most common carotenoid ␤ -carotene results in two molecules of retinaldehyde (retinal), which will be further converted to retinol by a reductive retinal reductase enzyme present in the same cell as BCO1. Previously, we studied the cell type-specific expression of BCO1 and found that the enzyme is also expressed in epithelia of several extraintestinal tissues, which suggested that these tissues have the capacity to directly convert locally stored carotenoids to vitamin A. Thus this may serve as a backup pathway of vitamin A synthesis during times of insufficient dietary intake of preformed vitamin A and provitamin A carotenoids.Recently, Kiefer et al. (2001) cloned and characterized a second carotenoid-cleaving enzyme termed ␤ -carotene 9 Ј ,10 Ј -monooxygenase (BCO2) because it catalyzes asymmetric cleavage of carotenoids, thus yielding one molecule of ␤ -apo-10 Ј -carotenal and one molecule of ␤ -ionone when ␤ -carotene is used as substrate. Interestingly, the BCO2 enzyme appears to accept a wider variety of substrates as compared with BCO1, including the acyclic carotenoid lycopene, which implies that this enzyme may have physiological roles other than providing precursors for vitamin A synthesis.BCO1 and BCO2 belong to a superfamily of nonheme iron-containing oxygenases, many of whose functions are unknown. The physiological role of BCO1 is now well establ...

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Section: Discussionmentioning

confidence: 82%

Cell Type-specific Expression of β-Carotene 9', 10'-Monooxygenase in Human Tissues

Lindqvist

Andersson

2005

J Histochem Cytochem.

116

100

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“…In our previous study, when β-carotene was directly supplied to the hepatocytes, we found that 1 μM β-carotene was similar in physiological concentrations and could attenuate oxidative stress induced by chronic ethanol intake (Yang et al, 2004). In addition, it has been reported that β-carotene induced neither significant cytotoxic nor genotoxic effects at concentrations ranging from 0.01 to 10 μM in rat primary hepatocytes (Alija et al, 2004). Therefore, we chose 1 μM β-carotene for investigating the antioxidant effect and possible protective mechanisms of β-carotene against ethanol-induced cytotoxicity in rat hepatocytes.…”

Section: Discussionmentioning

confidence: 94%

β‐Carotene exhibits antioxidant and anti‐apoptotic properties to prevent ethanol‐induced cytotoxicity in isolated rat hepatocytes

Peng

Chen

et al. 2010

Phytotherapy Research

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The study was designed to evaluate the effects of 1 microM beta-carotene on antioxidant status in ethanol-treated rat hepatocytes and investigate possible anti-apoptotic mechanisms of beta-carotene in protecting ethanol-induced cytotoxicity. The isolated rat hepatocytes were incubated for 48 h in a medium with or without alcohol (100 mM) and mu-carotene (1 microM) using the following groups: the control (C), beta-carotene (CB), ethanol (E), and ethanol + beta-carotene (EB) groups. The cell viability, antioxidative status, cytochrome P450 2E1 (CYP2E1) and caspase expressions in hepatocytes were measured. The E group demonstrated lower cell viability, glutathione (GSH) levels, and lipid peroxide accumulation in rat hepatocytes; meanwhile, CYP2E1, caspase-3, and caspase-9 expressions increased. In contrast, cell viability, GSH levels, and glutathione reductase (GRD) activity significantly increased while lipid peroxides and expressions of CYP2E1, casapse-3, and caspase-9 decreased in the EB group. The results suggest that ethanol treatment decreases cell viability in rat hepatocytes via induced oxidative stress. 1 muM beta-carotene decreased oxidative stress and prevented ethanol-induced cell death by inhibiting caspase-9 and caspase-3 expression.

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“…Although, in vitro studies demonstrated that carotenoid oxidation products exert effects that are either potentially beneficial or detrimental to human health (Khachik et al, 1995;Lakshminarayana et al, 2013;Zhang, Kotake-Nara, Ono, & Nagao, 2003;Alija, Bresgen, Sommerburg, Siems, & Eck, 2004;Hurst, Saini, Jin, Awasthi, & van Kuijk, 2005). Further, their active involvement in genetic regulation and expression with respect to specific functions is deserved to address health associated and nutrition-related disorders.…”

Section: Metabolism Of Oxygenated Carotenoidsmentioning

confidence: 99%

Metabolomics of carotenoids: The challenges and prospects – A review

Arathi

Sowmya

Vijay

et al. 2015

Trends in Food Science & Technology

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Considerable progress in carotenoids research has been made to understand the carotenoid metabolism in animals including human. Epidemiological and clinical studies have correlated with dietary intake of carotenoids on reduction of vitamin A deficiency, age-related macular degeneration, cancer and cardiovascular diseases. Recent findings demonstrate the existence of carotenoid metabolites in vivo and their efficacy have made greater insight on prospecting carotenoid metabolites. Owing to their biological activity, exploration of analytical methods for the characterization of carotenoid metabolites is considered to be important before addressing the stability and bioactivity. Although few studies are available on carotenoid metabolites, their structural characterization in biological samples require a substantial refining of analytical protocols like isolation, purification, prerequisite of equipment parameters and robustness in hyphenated techniques.Recently, researchers have focused on biotransformation of carotenoids and made an attempt to screen their metabolites by high-throughput analytical strategies. However, till date there is no detailed analytical techniques available to fingerprint carotenoid metabolites, due to interference with complex biological matrices. This review highlights the carotenoid metabolism, possible bioconversion and available bio-analytical techniques to characterize metabolites in vivo. Further, advancement in sensitivity, mode of ionization and fragmentation patterns of metabolites were also discussed. The identification of carotenoid metabolites in system specific will have further insight in the emerging field of nutritional metabolomics.

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Cytotoxic and genotoxic effects of -carotene breakdown products on primary rat hepatocytes

Cited by 55 publications

References 30 publications

Cell Type-specific Expression of β-Carotene 9', 10'-Monooxygenase in Human Tissues

Cell Type-specific Expression of β-Carotene 9', 10'-Monooxygenase in Human Tissues

β‐Carotene exhibits antioxidant and anti‐apoptotic properties to prevent ethanol‐induced cytotoxicity in isolated rat hepatocytes

Metabolomics of carotenoids: The challenges and prospects – A review

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