A Highly Toxic Coplanar Polychlorinated Biphenyl Compound Suppresses Δ5 and Δ6 Desaturase Activities Which Play Key Roles in Arachidonic Acid Synthesis in Rat Liver

Matsusue, Kimihiko; Ishii, Yuji; Ariyoshi, Noritaka; Oguri, Kazuta

doi:10.1021/tx990104r

Cited by 32 publications

(25 citation statements)

References 53 publications

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“…There is also evidence that elevated levels of linoleic acid may enhance the cellular availability of PCBs [16]. Furthermore, coplanar PCBs can suppress delta 5 and 6 desaturase activities, thus disrupting the synthesis of fatty acid precursors for eicosanoid metabolism [17]. Our own data from plasma and livers of LDL receptor-deficient mice support the hypothesis that treatment with PCBs can facilitate clearance of linoleic acid from plasma into vascular tissues [18].…”

Section: Introductionsupporting

confidence: 68%

Changing ratios of omega-6 to omega-3 fatty acids can differentially modulate polychlorinated biphenyl toxicity in endothelial cells

Wang

Reiterer

Toborek

et al. 2008

Chemico-Biological Interactions

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Exposure to persistent organic pollutants, such as polychlorinated biphenyls (PCBs) can cause endothelial cell (EC) activation by inducing pro-inflammatory signaling pathways. Our previous studies indicated that linoleic acid (LA, 18:2), a major omega-6 unsaturated fatty acid in the American diet, can potentiate PCB77-mediated inflammatory responses in EC. In addition, omega-3 fatty acids (such as α-linolenic acid, ALA, 18:3) are known for their anti-inflammatory properties. We tested the hypothesis that mechanisms of PCB-induced endothelial cell activation and inflammation can be modified by different ratios of omega-6 to omega-3 fatty acids. EC were pretreated with LA, ALA, or different ratios of these fatty acids, followed by exposure to PCB77. PCB77-induced oxidative stress and activation of the oxidative stress sensitive transcription factor nuclear factor κB (NF-κB) were markedly increased in the presence of LA and diminished by increasing the relative amount of ALA to LA. Similar protective effects by increasing ALA were observed by measuring NF-κB-responsive genes, such as vascular cell adhesion molecule-1 (VCAM-1) and cyclooxygenase-2 (COX-2). COX-2 catalyzes the rate limiting step of the biosynthesis of prostaglandin E 2 (PGE 2 ). PCB77 exposure also increased PGE 2 levels, which were down-regulated with relative increasing amounts of ALA to LA. The present studies suggest that NF-κB is a critical player in the regulation of PCB-induced inflammatory markers as modulated by omega-6 and omega-3 fatty acids.

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Section: Introductionsupporting

confidence: 68%

Changing ratios of omega-6 to omega-3 fatty acids can differentially modulate polychlorinated biphenyl toxicity in endothelial cells

Wang

Reiterer

Toborek

et al. 2008

Chemico-Biological Interactions

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“…Most experimental evidence supports that chronic inflammation and dysfunction of the vascular endothelium, through an increasing cellular oxidative stress and AhR-mediated mechanisms, are critical events in the toxicity of DL-PCBs on hypertension. [48][49][50][51] In addition, experimental studies found that DL-PCBs have the ability to reduce the synthesis of physiologically essential long-chain unsaturated fatty acids 52 and, consequently, to alter the endothelial cell lipid and metabolism.…”

Section: Discussionmentioning

confidence: 99%

Association Between Dietary Intake of Polychlorinated Biphenyls and the Incidence of Hypertension in a Spanish Cohort

et al. 2015

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Polychlorinated biphenyls are persistent organic pollutants that are consumed because of their bioaccumulation through the food chain. Evidence from different sources suggests a positive association between polychlorinated biphenyls exposure and the incidence of hypertension. However, no previous prospective study has investigated this potential relationship in adults. We prospectively assessed the association between dietary intake of polychlorinated biphenyls and the incidence of hypertension in a large cohort. The Seguimiento Universidad de Navarra project is a Spanish cohort of university graduates, most of them health professionals. We included 14521 participants, initially free of hypertension, who were followed-up for a median of 8.3 years. Dietary intake of polychlorinated biphenyls was assessed at baseline through a previously validated 136-item semiquantitative food frequency questionnaire. The published concentration levels of polychlorinated biphenyls measured in samples of food consumed in Spain were used to estimate dietary intake. Multivariable Cox regression models were fitted to estimate hazard ratios and 95% confidence interval for incident hypertension. During follow-up, 1497 incident cases of medically diagnosed hypertension were identified. After adjusting for total energy intake and for potential confounders, participants in the fifth quintile of total polychlorinated biphenyls intake were at higher risk of developing hypertension (adjusted hazard ratio, 1.43 [95% confidence interval, 1.09–1.88; P for trend 0.017]) compared with those in the first quintile. In this Mediterranean cohort, dietary intake of polychlorinated biphenyls, estimated using a food frequency questionnaire, was associated with a higher risk of developing hypertension during follow-up. Nevertheless, further longitudinal studies are needed to confirm our results.

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“…Asais-Braesco et al (1990) reported that a single injection of PCB-77 resulted in a marked change in the fatty acid composition of rat hepatic microsomal fractions. Also, Matsusue et al (1999) found that coplanar PCBs have a significant effect on the reduced synthesis of physiologically essential long-chain unsaturated fatty acids, such as arachidonic acid in rat liver, by suppressing delta-5 and delta-6 desaturase activities and thus allowing the omega-6 parent fatty acid, linoleic acid, to accumulate.…”

mentioning

confidence: 99%

Dietary Fat Interacts with PCBs to Induce Changes in Lipid Metabolism in Mice Deficient in Low-Density Lipoprotein Receptor

Hennig¹,

Reiterer²,

Toborek³

et al. 2005

Environ Health Perspect

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There is evidence that dietary fat can modify the cytotoxicity of polychlorinated biphenyls (PCBs) and that coplanar PCBs can induce inflammatory processes critical in the pathology of vascular diseases. To test the hypothesis that the interaction of PCBs with dietary fat is dependent on the type of fat, low-density lipoprotein receptor–deficient (LDL-R−/−) mice were fed diets enriched with either olive oil or corn oil for 4 weeks. Half of the animals from each group were injected with PCB-77. Vascular cell adhesion molecule-1 (VCAM-1) expression in aortic arches was non-detectable in the olive-oil–fed mice but was highly expressed in the presence of PCB-77. PCB treatment increased liver neutral lipids and decreased serum fatty acid levels only in mice fed the corn-oil–enriched diet. PCB treatment increased mRNA expression of genes involved in inflammation, apoptosis, and oxidative stress in all mice. Upon PCB treatment, mice in both olive- and corn-oil–diet groups showed induction of genes involved in fatty acid degradation but with up-regulation of different key enzymes. Genes involved in fatty acid synthesis were reduced only upon PCB treatment in corn-oil–fed mice, whereas lipid transport/export genes were altered in olive-oil–fed mice. These data suggest that dietary fat can modify changes in lipid metabolism induced by PCBs in serum and tissues. These findings have implications for understanding the interactions of nutrients with environmental contaminants on the pathology of inflammatory diseases such as atherosclerosis.

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A Highly Toxic Coplanar Polychlorinated Biphenyl Compound Suppresses Δ5 and Δ6 Desaturase Activities Which Play Key Roles in Arachidonic Acid Synthesis in Rat Liver

Cited by 32 publications

References 53 publications

Changing ratios of omega-6 to omega-3 fatty acids can differentially modulate polychlorinated biphenyl toxicity in endothelial cells

Changing ratios of omega-6 to omega-3 fatty acids can differentially modulate polychlorinated biphenyl toxicity in endothelial cells

Association Between Dietary Intake of Polychlorinated Biphenyls and the Incidence of Hypertension in a Spanish Cohort

Dietary Fat Interacts with PCBs to Induce Changes in Lipid Metabolism in Mice Deficient in Low-Density Lipoprotein Receptor

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