2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) alters the mRNA expression of critical genes associated with cholesterol metabolism, bile acid biosynthesis, and bile transport in rat liver: A microarray study

Fletcher, Nick; Wahlström, David; Lundberg, Rebecca; Nilsson, Charlotte B.; Nilsson, Karolina; Stockling, Kenneth; Hellmold, Heike; Håkansson, Helen

doi:10.1016/j.taap.2004.12.003

Cited by 151 publications

(116 citation statements)

References 119 publications

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“…In the present study, a significant decrease in Na (Jabs et al 1989;Schwartzman et al 1985;Lear et al 1990;Therien and Blostein 2000). In addition, altered expression of Na + K + -ATPase in hepatic tissues during TCDD treatment has been reported earlier by Fletcher et al (2005) and Peterson et al (1979).…”

Section: Discussionsupporting

confidence: 86%

Fish oil rich in eicosapentaenoic acid protects against oxidative stress-related renal dysfunction induced by TCDD in Wistar rats

Palaniswamy

Vishwanadha

Singaravelu

2014

Cell Stress and Chaperones

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Humans are systemically exposed to persistent organic pollutants, of which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has become a major environmental concern. Exposure to TCDD results in a wide variety of adverse health effects which is mediated by oxidative stress through CYP1A1 activation and arachidonic acid metabolites. Eicosapentaenoic acid (EPA) exhibits antioxidant property and competes with arachidonic acid in membrane phospholipids and produces anti-inflammatory EPA derivatives. Since both EPA and its derivatives have been reported to enhance the antioxidant mechanism, the present study aimed at studying whether EPA could offer protection against TCDDinduced oxidative stress and nephrotoxicity in Wistar rats. Estimation of kidney markers (serum urea and creatinine) and histopathological studies revealed that EPA treatment significantly reduced TCDD-induced renal damage. TCDDinduced oxidative damage was reflected in a significant increase in CYP1A1 activity and lipid peroxide levels with a concomitant decline in non-enzymic antioxidant (GSH) and various enzymic antioxidants such catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GST), and glutathione peroxidase (GPx). In addition, TCDD-induced oxidative stress also resulted in decline in Na + -K + and Mg 2+ATPases activities with increase in Ca 2+ ATPases activity. Oral treatment with EPA showed a significant cytoprotection against TCDD-induced renal oxidative stress by decreased CYP1A1 activity and enhanced antioxidant status. TCDD-induced alterations in ATPase enzyme activities were also prevented by EPA treatment. Our results show clear evidence that EPA ameliorates TCDD-induced oxidative stress and kidney damage; thus suggest the potential of EPA as an effective therapeutic agent against toxic effects mediated through redox imbalance.

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Section: Discussionsupporting

confidence: 86%

Fish oil rich in eicosapentaenoic acid protects against oxidative stress-related renal dysfunction induced by TCDD in Wistar rats

Palaniswamy

Vishwanadha

Singaravelu

2014

Cell Stress and Chaperones

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“…Because TCDD did not have any effect on the hepatic expression of BSEP and MRP2, it is suggested that one of the mechanisms underlying the elevated level of bile acids in the feces is attenuated resorption in the small intestine rather than excess release from the liver. Also, in accordance with a previous report, 25) TCDD reduced or tended to reduce the hepatic expression of CYP7A1 and NTCP. CYP7A1 oxidizes cholesterol to its 7-hydroxy derivative, a rate-limiting step in bile acid synthesis, and NTCP is involved in the enterohepatic circulation of bile acids: that is, this protein transports bile acids back to the liver.…”

Section: Discussionsupporting

confidence: 93%

“…In this context, a previous study using a DNA microarray analysis also suggested that TCDD alters the hepatic expression of genes associated with the metabolism of cholesterol, and the biosynthesis and transport of bile acids. 25) As established already, bile acids play an important role in the intestinal absorption of lipids and cholesterol, [26][27][28] steroid metabolism 29) and the biliary secretion of lipids and xenobiotics. 30) Therefore, an excess of bile acids may be linked to TCDD-produced wasting syndrome and the impaired utilization of lipids.…”

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confidence: 99%

Dioxin-Produced Alteration in the Profiles of Fecal and Urinary Metabolomes: A Change in Bile Acids and Its Relevance to Toxicity

Kakizuka

Takeda

Komiya

et al. 2015

Biological & Pharmaceutical Bulletin

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This study investigated dioxin-induced changes in metabolomes in pubertal rat excrement. The administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or restricting dietary intake (pair-fed group) markedly altered the metabolomic profile including lipids, hormones, and vitamins in the urine and feces. TCDD caused an increase in the fecal chenodeoxycholic acid and taurocholic acid content and in urinary adrenaline and 17β-estradiol, while the urinary melatonin level was reduced by TCDD. These changes were not observed in the pair-fed group. In accordance with the elevated level of fecal bile acids, TCDD reduced the intestinal expression of the apical sodium-dependent bile salt transporter, which plays a role in resorbing bile acids from the bile duct. In addition, CYP7A1, a rate-limiting enzyme for bile acid biosynthesis, was attenuated by TCDD treatment, although TCDD induced hepatic CYP8B1, an enzyme essential for cholic acid synthesis. Supplying cholic acid or chenodeoxycholic acid to TCDD-exposed rats tended to restore the TCDD-produced reduction in serum triglycerides, whereas no similar trend was observed in wasting syndrome and lipid accumulation in the liver. These results suggest that: 1) TCDD alters the circulating levels of bile acids and hormones via a mechanism distinct from an attenuation in dietary intake, although the majority of TCDDinduced changes in nutrient contents in the excrement is due to a reduction in food intake; and 2) TCDD facilitates the excretion of bile acids and disrupts their biosynthesis, resulting in the disturbance of lipid homeostasis.

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“…Activation of Ahr by those drugs induces the transcription of genes containing XRE sites in their promoter regions (1,4). Known Ahr targets include loci encoding cytochrome P450 family members in charge of the phase I detoxification response (5-9), phase II detoxification proteins (10 -12), metabolism-related enzymes (13)(14)(15), and many other molecules (16,17).…”

mentioning

confidence: 99%

Transcriptional Factor Aryl Hydrocarbon Receptor (Ahr) Controls Cardiovascular and Respiratory Functions by Regulating the Expression of the Vav3 Proto-oncogene

Sauzeau

Carvajal-González

Riolobos

et al. 2011

Journal of Biological Chemistry

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2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) alters the mRNA expression of critical genes associated with cholesterol metabolism, bile acid biosynthesis, and bile transport in rat liver: A microarray study

Cited by 151 publications

References 119 publications

Fish oil rich in eicosapentaenoic acid protects against oxidative stress-related renal dysfunction induced by TCDD in Wistar rats

Fish oil rich in eicosapentaenoic acid protects against oxidative stress-related renal dysfunction induced by TCDD in Wistar rats

Dioxin-Produced Alteration in the Profiles of Fecal and Urinary Metabolomes: A Change in Bile Acids and Its Relevance to Toxicity

Transcriptional Factor Aryl Hydrocarbon Receptor (Ahr) Controls Cardiovascular and Respiratory Functions by Regulating the Expression of the Vav3 Proto-oncogene

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