Green tea diet decreases PCB 126-induced oxidative stress in mice by up-regulating antioxidant enzymes

Abstract

Superfund chemicals such as polychlorinated biphenyls pose a serious human health risk due to their environmental persistence and link to multiple diseases. Selective bioactive food components such as flavonoids have been shown to ameliorate PCB toxicity, but primarily in an in vitro setting. Here, we show that mice fed a green tea-enriched diet and subsequently exposed to environmentally relevant doses of coplanar PCB exhibit decreased overall oxidative stress primarily due to the upregulation of a battery of antioxidant enzymes. C57BL/6 mice were fed a low fat diet supplemented with green tea extract (GTE) for 12 weeks and exposed to 5 μmol PCB 126/kg mouse weight (1.63 mg/kg-day) on weeks 10, 11 and 12 (total body burden: 4.9 mg/kg). F2-Isoprostane and its metabolites, established markers of in vivo oxidative stress, measured in plasma via HPLC-MS/MS exhibited five-fold decreased levels in mice supplemented with GTE and subsequently exposed to PCB compared to animals on a control diet exposed to PCB. Livers were collected and harvested for both mRNA and protein analyses, and it was determined that many genes transcriptionally controlled by AhR and Nrf2 proteins were upregulated in PCB-exposed mice fed the green tea supplemented diet. An increased induction of genes such as SOD1, GSR, NQO1 and GST, key antioxidant enzymes, in these mice (green tea plus PCB) may explain the observed decrease in overall oxidative stress. A diet supplemented with green tea allows for an efficient antioxidant response in the presence of PCB 126 which supports the emerging paradigm that healthful nutrition may be able to bolster and buffer a physiological system against the toxicities of environmental pollutants.

Exercise protects against PCB-induced inflammation and associated cardiovascular risk factors

“…Wang, Mehendale, Calway, & Yuan, 2011). Evidence from our laboratory suggests that antioxidant nutrients and related bioactive compounds found in fruits and vegetables protect against environmental toxic insult to the vascular endothelium by increasing antioxidant defense and by down-regulation of proinflammatory signaling (Hennig et al, 2007; Newsome et al, 2014); however, the role of exercise remains largely unknown.…”

“…Briefly, homogenates were extracted in acetonitrile with the appropriate internal standards, dried under N 2 and reconstituted (Newsome et al, 2014). Measurement of urinary F 2 -Isoprostanes (F 2 -IsoPs) is considered the gold standard for assessment of in vivo oxidative stress (Morrow, 2005), and the assay was performed as described by us elsewhere (Newsome et al, 2014).…”

“…Briefly, homogenates were extracted in acetonitrile with the appropriate internal standards, dried under N 2 and reconstituted (Newsome et al, 2014). Measurement of urinary F 2 -Isoprostanes (F 2 -IsoPs) is considered the gold standard for assessment of in vivo oxidative stress (Morrow, 2005), and the assay was performed as described by us elsewhere (Newsome et al, 2014). After extractions were performed, plasma, tissue, and urinary levels of PCB 77, hydroxyl metabolites, and F 2 -IsoPs were analyzed using a Shimadzu ultra-fast liquid chromatography system coupled with an AB Sciex 4000-Qtrap hybrid linear ion trap triple quadrupole mass spectrometer in multiple reaction monitoring (MRM) mode (Newsome et al, 2014).…”

“…Total mRNA was extracted from liver using the TRIZOL reagent (Invitrogen Life Technologies, Carlsbad, CA) according to the manufacturer’s protocol and as reported elsewhere (Newsome et al, 2014). Primer sequences [see Online Resource, Table S1) for SYBR Green chemistry were designed using the Primer Express Software 3.0 for RT-PCR (Applied Biosystems) and procured from Integrated DNA Technologies, Inc. (Coralville, IA).…”

The modulation of carbonyl reductase 1 by polyphenols

“…Besides the direct scavenging of reactive oxygen species, metal chelating activity and the reduction of a-tocopheryl radicals (reviewed in Prochazkova et al, 2011), the antioxidant properties of flavonoids are also probably based on the ability to increase the expression of several antioxidant enzymes (e.g. glutathione S-transferases, NADPH:quinone oxidoreductase 1 and g-glutamyl cysteine synthetase) via the transcription factor of an Nrf2-dependent signal transduction pathway (Newsome et al, 2014;Ramprasath et al, 2014). Nevertheless, pro-oxidant properties of flavonoids have also been described under certain circumstances and several mechanisms of this pro-oxidative activity have been proposed (reviewed in Prochazkova et al, 2011).…”