Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association

Publications in this journal

• Article: Preventive effects of p-coumaric acid on cardiac hypertrophy and alterations in electrocardiogram, lipids, and lipoproteins in experimentally induced myocardial infarcted rats.

  Abhro Jyoti Roy, P Stanely Mainzen Prince
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  ABSTRACT: The present study evaluated the preventive effects of p-coumaric acid on cardiac hypertrophy and alterations in electrocardiogram, lipids, and lipoproteins in experimentally induced myocardial infarcted rats. Rats were pretreated with p-coumaric acid (8 mg/kg body weight) daily for a period of 7 days and then injected with isoproterenol (100 mg/kg body weight) on 8(th) and 9(th) day to induce myocardial infarction. Myocardial infarction induced by isoproterenol was indicated by increased level of cardiac sensitive marker and elevated ST-segments in the electrocardiogram. Also, the levels/concentrations of serum and heart cholesterol, triglycerides and free fatty acids were increased in myocardial infarcted rats. Isoproterenol also increased the levels of serum low density and very low density lipoprotein cholesterol and decreased the levels of high density lipoprotein cholesterol. It also enhanced the activity of liver 3-hydroxy-3 methyl glutaryl-Coenzyme-A reductase. p-Coumaric acid pretreatment revealed preventive effects on all the biochemical parameters and electrocardiogram studied in myocardial infarcted rats. The in vitro study confirmed the free radical scavenging property of p-coumaric acid. Thus, p-coumaric acid prevented cardiac hypertrophy and alterations in lipids, lipoproteins, and electrocardiogram, by virtue of its antihypertrophic, antilipidemic, and free radical scavenging effects in isoproterenol induced myocardial infarcted rats.
  Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 05/2013;
• Article: Inhibitory effects of astaxanthin, β-cryptoxanthin, canthaxanthin, lutein, and zeaxanthin on cytochrome P450 enzyme activities.

  Yu Fen Zheng, Soo Hyeon Bae, Min Jo Kwon, Jung Bae Park, Hye Duck Choi, Wan Gyoon Shin, Soo Kyung Bae
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  ABSTRACT: Astaxanthin, β-cryptoxanthin, canthaxanthin, lutein and zeaxanthin, the major xanthophylls, are widely used in food, medicine, and health care products. To date, no studies regarding the inhibitory effects of these xanthophylls on the nine CYPs isozymes have been reported. This study investigated the reversible and time-dependent inhibitory potentials of five xanthophylls on CYPs activities in vitro. The reversible inhibition results showed that the five compounds had only a weak inhibitory effect on the nine CYPs. Lutein did not inhibit the nine CYPs activities. Astaxanthin weakly inhibited CYP2C19, with an IC50 of 16.2 μM; and β-cryptoxanthin weakly inhibited CYP2C8, with an IC50 of 13.8 μM. In addition, canthaxanthin weakly inhibited CYP2C19 and CYP3A4/5, with IC50 values of 10.9 and 13.9 μM, respectively. Zeaxanthin weakly inhibited CYP3A4/5, with an IC50 of 15.5 μM. However, these IC50 values were markedly greater than the Cmax values reported in humans. No significant IC50 shift was observed in the time-dependent inhibition screening. Based on these observations, it is unlikely that these five xanthophylls from the diet or nutritional supplements alter the pharmacokinetics of drugs metabolized by CYPs. These findings provide some useful information for the safe use of these five xanthophylls in clinical practice.
  Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 05/2013;
• Article: Bioaccessibility of Metals in Fish, Shellfish, Wild Game, and Seaweed Harvested in British Columbia, Canada.

  Brian D Laird, Hing Man Chan
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  ABSTRACT: Fish, shellfish, wild game, and seaweed are important traditional foods that are essential to the physical and cultural well-being of Indigenous peoples in Canada. The goal of this study was to measure the concentration and bioaccessibility of As, Cd, Hg, Se, Cu and Mn in 45 commonly consumed traditional foods collected by harvested by the First Nations Food, Nutrition, and Environment Study (FNFNES) from 21 First Nations communities in British Columbia, Canada, in 2008-2009. A significant and negative correlation was observed between Hg concentration and Hg bioaccessibility. Metal bioaccessibility tended to be high; median values ranging between 52% (Mn) and 83% (Cu). The notable exceptions were observed for As in wild game organs (7-19%) and rabbit meat (4%) as well as Hg in salmon eggs (10%). Results of Principal Components Analysis confirmed the unique pattern of bioaccessibility of As and Hg in traditional foods, suggesting that, unlike other metals, As and Hg bioaccessibility are not simply controlled by food digestibility under the operating conditions of the in vitro model. These data provide useful information for dietary contaminant risk assessment and intake assessments of essential trace elements.
  Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 05/2013;
• Article: Potential role of ATP-binding cassette transporters in the intestinal transport of rhein.

  Ling Ye, Linlin Lu, Ye Li, Shan Zeng, Xiaoshan Yang, Weiying Chen, Qian Feng, Wei Liu, Lan Tang, Zhongqiu Liu
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  ABSTRACT: Rhein, a lipophilic anthraquinone, exhibits anti-inflammatory and anti-tumor activities; however, it is hepatotoxic. ATP-binding cassette transporters, including P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and multidrug resistance-associated protein 2 (MRP2), can pump toxicants from gut epithelial cells back into the intestinal lumen to prevent poisoning. We investigated their roles in rhein transport using a rat intestinal perfusion model and Caco-2, MDCKII-MDR1 (high expression of P-gp), MDCKII-BCRP (high expression of BCRP) and MDCKII-MRP2 (high expression of MRP2) cell models. The permeability of rhein in the duodenum significantly increased with increasing perfused concentration of rhein in the rat model, suggesting that efflux transporters were involved in rhein transport. In the Caco-2 cells, the permeability of rhein from the basolateral (B) to the apical (A) was significantly higher than that from A to B. In the presence of BCRP or MRP2 inhibitor, the permeability of rhein significantly decreased from B to A direction. In the MDCKII-BCRP cells, rhein was more permeable in B to A side than that in the opposite side. However, no significant differences of rhein permeability were observed in two directions in both MDCKII-MDR1 and MDCKII-MRP2 cells. Taken together, these results suggested that only BCRP was involved in rhein transport.
  Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 05/2013;
• Article: Nano-Titanium Dioxide Induced Cardiac Injury in Rat under Oxidative Stress.

  Baoyong Sha, Wei Gao, Shuqi Wang, Wei Li, Xuan Liang, Feng Xu, Tian Jian Lu
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  ABSTRACT: Heart diseases, which are related to oxidative stress (OS), negatively affect millions of people from kids to the elderly. Titanium dioxide (TiO2) has widespread applications in our daily life, especially nanoscale TiO2. Compared to the high risk of particulate matter (⩽2.5 μm) in air to heart disease patients, related research of TiO2 on diseased body is still unknown, which suggest us to explore the potential effects of nanoscale and microscale TiO2 to heart under OS conditions. Here, we used alloxan to induce OS conditions in rat, and investigated the response of heart tissue to TiO2 in healthy and alloxan treated rats. Compared with NMs treatment only, the synergistic interaction between OS conditions and nano-TiO2 significantly reduced the heart-related function indexes, inducing pathological changes of myocardium with significantly increased levels of cardiac troponin I and creatine kinase-MB. In contrast with the void response of micro-TiO2 to heart functions in alloxan treated rats, aggravation of OS conditions might play an important role in cardiac injury after alloxan and nano-TiO2 dual exposure. Our results demonstrated that OS conditions enhanced the adverse effects of nano-TiO2 to heart, suggesting that the use of NMs in stressed conditions (e.g., drug delivery) needs to be carefully monitored.
  Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 05/2013;
• Article: 6-acetonyl-5,6-dihydrosanguinarine (ADS) from Chelidonium majus L. triggers proinflammatory cytokine production via ROS-JNK/ERK-NFκB signaling pathway.

  Dong Hyeok Kim, Jihye Lee, Su-Jong Park, Sang-Seok Oh, Suk Kim, Dae Wook Kim, Ki Hun Park, Kwang Dong Kim
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  ABSTRACT: Chelidonium majus L. is an herbal plant that is commonly used in Western phytotherapy and traditional Chinese medicine for diuretic, antitussive, eye-regenerative, anti-osteoporotic, and radioprotective purposes. In this study, we purified 6-acetonyl-5,6-dihydrosanguinarine (ADS) from C. majus and investigated its immune-stimulatory effect. We found that ADS has the potential to induce the inflammatory cytokines TNF-α, IL-6, and IL-8 in macrophages and dendritic cells (DCs), that NFκB activation is a critical mediator of ADS-induced cytokine production, and that the activation of NFκB was dependent on reactive oxygen species (ROS). ADS induced phosphorylation of ERK and JNK, which was also associated with NFκB activation; phosphorylarion and cytokine production were inhibited by ROS scavenger and by specific MAPK inhibitors. Taken together, the results suggest that ADS from C. majus, as a positive immune modulator, induces inflammatory cytokines that might improve immunity, via the ROS-ERK/JNK-NFκB pathway.
  Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 05/2013;
• Article: Investigation on the interaction of the toxicant, gentian violet, with bovine hemoglobin.

  Yan Liu, Jingjing Lin, Mingmao Chen, Ling Song
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  ABSTRACT: Gentian violet (GV) is a well-known triarylmethane dye that is used in aquacultural, industrial and medicinal fields. But concerns in growing number have been paid to its potential health problems to human beings and its hazardous effects to environment. Herein, the toxic interaction of GV with bovine hemoglobin (BHb) was investigated by a series of spectroscopic methods and molecular modeling method. The fluorescence emission profile exhibited a remarkable quenching upon addition of GV to the buffered aqueous solution of BHb and the analysis of results revealed the dominant role of static quenching mechanism in GV-BHb interaction. The negative ΔH and positive ΔS values demonstrated that the electrostatic interactions mainly stabilized this toxicant-protein complex. Synchronous fluorescence, UV-vis absorption and CD spectroscopic studies proved that the conformational change of BHb was induced by GV's combination. Molecular modeling studies exhibited the binding mode of GV-BHb complex and the detailed information of related driving forces. During the 1H nuclear magnetic resonance spectra (1H NMR) study, the chemical shift perturbation and spin-lattice relaxation times of different protons were further used to investigate the interaction of GV with BHb and the results indicated that GV bound orientationally to BHb.
  Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 05/2013;
• Article: Bioconcentration of chromium in edible mushrooms: influence of environmental and genetic factors.

  M A García, J Alonso, M J Melgar
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  ABSTRACT: Chromium concentrations were determined in 167 samples of wild edible mushrooms, collected from three different sites (urban, traffic and pastureland areas) in Lugo (NW Spain). The hymenophore (H) and the rest of the fruiting body (RFB) were analysed separately. The analyses were performed using inductively coupled plasma optical emission spectrometry (ICP-OES). The highest mean chromium levels (mg/kg dry weight) of 3.5 and 8.0, 4.5 and 6.2, and 6.2 and 4.3 were found in Lycoperdon utriforme, Coprinus comatus and Agaricus campestris in H and RFB, respectively. The highest concentrations of chromium were observed in terrestrial saprophytic species in relation to mycorrhizal species. With respect to the underlying substrates, chromium concentration was lowest in the pastureland area (24.6 mg/kg dw). All mushroom species were bioexclusors of chromium (BCF<1) with statistically significant differences (p<0.001). The consumption of mushrooms harvested from the areas investigated poses no toxicological risk to human health due to chromium.
  Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 05/2013;
• Article: Evaluation of genotoxicity of nitrile fragrance ingredients using in vitro and in vivo assays.

  S P Bhatia, V T Politano, A M Api
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  ABSTRACT: Genotoxicity studies were conducted on a group of 8 fragrance ingredients that belong to the nitrile family. These nitriles are widely used in consumer products however there is very limited data in the literature regarding the genotoxicity of these nitriles. The 8 nitriles were assessed for genotoxicity using an Ames test, in-vitro chromosome aberration test or in-vitro micronucleus test. The positive results observed in the in-vitro tests were further investigated using an in-vivo micronucleus test. The results from these different tests were compared and these 8 nitriles are not considered to be genotoxic. Dodecanitrile and 2,2,3-trimethylcyclopent-3-enylacetonitrile were negative in the in-vitro chromosome aberration test and in-vitro micronucleus test, respectively. While citronellyl nitrile, 3-methyl-5-phenylpentanenitrile, cinnamyl nitrile, and 3-methyl-5-phenylpent-2-enenitrile revealed positive results in the in-vitro tests, but confirmatory in-vivo tests determined these nitriles to be negative in the in-vivo micronucleus assay. The remaining two nitriles (benzonitrile and α-cyclohexylidene benzeneacetonitrile) were negative in the in-vivo micronucleus test. This study aims to evaluate the genotoxicity potential of these nitriles as well as enrich the literature with genotoxicity data on fragrance ingredients.
  Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 04/2013;
• Article: Hydroxytyrosyl alkyl ether derivatives inhibit platelet activation after oral administration to rats.

  Javier Muñoz-Marín, José Pedro De La Cruz, José Julio Reyes, Juan Antonio López-Villodres, Ana Guerrero, Inmaculada López-Leiva, José Luis Espartero, María Teresa Labajos, José Antonio González-Correa
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  ABSTRACT: The low lipophilicity of hydroxytyrosol (HT) has motivated efforts to synthesize homologous series with better lipid solubility, such as the ethers, which are more lipophilic than HT. Because HT inhibits platelet aggregation, the aim of the study was to assess the possible anti-platelet effect of five HT ether derivatives (ethyl, butyl, hexyl, octyl and dodecyl) after oral administration to rats. Whole blood collagen-induced platelet aggregation and calcium-induced thromboxane B2 (TxB2), aortic 6-keto-prostaglandin F1α (6-keto-PGF1α) and nitrites + nitrates, plasma concentration of lipid peroxides (TBARS) and red blood cell content of reduced glutathione (GSH) were measured. The administration of 20 mg/kg/day inhibited platelet aggregation, TxB2 and TBARS in a non-linear manner related to the length of the carbon chain, with a cut-off effect in the hexyl derivative. Aortic nitrite and red blood cell GSH production were also increased. The aortic production of 6-keto-PGF1α was unaltered except in the group treated with the dodecyl derivative. The administration of 50 mg/kg/day showed a similar pharmacodynamic profile but without the non-linear effect. In conclusion, HT ethers, especially the hexyl derivative, are a potential alternative to hydroxytyrosol, and their effect merits additional research to determine their role in the prophylaxis of vascular disease.
  Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 04/2013;
• Article: Effects of red wine intake on human salivary antiradical capacity and total polyphenol content.

  Elena Maria Varoni, Sara Vitalini, Daniele Contino, Giovanni Lodi, Paolo Simonetti, Claudio Gardana, Andrea Sardella, Antonio Carrassi, Marcello Iriti
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  ABSTRACT: The protective effects of grape polyphenols have been reported on oral health, though unreasonable alcohol consumption represents a risk factor for developing oral cancer. The possible effects of red wine consumption on salivary antiradical activity were investigated in health volunteers for the first time, to the best of our knowledge. Time-course (from 0 min to 240 min) changes of salivary radical-scavenging capacity were measured by the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS(·)(+)) and 2,2-diphenyl-1-picrylhydrazyl (DPPH(·)) assays, in twelve healthy volunteers, after the intake of red wine (125 mL), a capsule of red wine extract (300 mg) or water (125 mL). Furthermore, time course of salivary total polyphenol levels, detected by the Folin-Ciocalteu colorimetric method, was also determined. Both ABTS and DPPH tests showed that red wine consumption did not increase salivary antiradical activity in volunteers. Conversely, red wine extract administration caused a marked rise in salivary ABTS radical-scavenging capacity within 30 min, followed by a plateau up to 240 min. The same treatment also raised salivary DPPH radical-scavenging activity at any time point, though to a minor extent. The highest salivary polyphenol concentration was reached 30 min after wine drinking, followed by a steady decrease up to 240 min. Wine drinking was not associated to a reduced salivary antiradical capacity. However, wine extract greatly improved the salivary antioxidant status.
  Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 04/2013;
• Article: Gene expression profiling and pathway analysis of hepatotoxicity induced by triptolide in Wistar rats.

  Jiaying Wang, Zhenzhou Jiang, Jinzi Ji, Xinzhi Wang, Tao Wang, Yun Zhang, Ting Tai, Mi Chen, Lixin Sun, Xia Li, Luyong Zhang
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  ABSTRACT: Triptolide (TP), a major component of TWHF, is widely used to treat rheumatoid arthritis, systemic lupus erythematosus, nephritis and leprosy. However, its clinical use is limited by hepatotoxicity. To further elucidate the underlying mechanism of its hepatotoxic effects, hepatic gene expression profiles were analyzed. TP (1000 and 300 μg/kg) was orally administered to Wistar rats for 14 days. Current study indicated that female rats were more sensitive to TP-induced hepatotoxicity than males. Genome-wide microarray analyses identified 3329 differentially expressed genes in liver of female rats. Analyses of these genes identified over-represented functions associated with insulin signaling pathway, glucose metabolism, cell cycle, oxidative stress and apoptosis, which were consistent with the results of significant increase of Caspase-3 activity and reduction of serum glucose, GSH/GSSG ratio, glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities, liver glycogen. In addition, it was observed for the first time that glucocorticoids and IGF1 might get involved in TP-induced hepatotoxicity. These data suggest that TP treatment could alter the hepatic redox status, reduce serum glucose and induce hepatocyte apoptosis, consistent with the differential expression of genes involved in insulin signaling pathway, glucose metabolism pathway and cell stress pathway, all of which might contribute to the overall TP-induced hepatotoxicity.
  Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 04/2013;
• Article: High salt intake does not produce additional impairment in the coronary artery relaxation of spontaneously hypertensive aged rats.

  Maylla R Simões, Lorena B Furieri, Ludimila Forechi, Marcelo P Baldo, Sérgio L Rodrigues, Mercedes Salaices, Dalton V Vassallo, José Geraldo Mill
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  ABSTRACT: The effect of a salt-based diet on the coronary responsiveness in aged hypertensive rats (SHR) still unclear. We investigated the effects of high salt intake on the relaxation properties of coronary arteries of aged SHRs. Male SHR (32 week-old) received drink water (SHR) or 1% NaCl solution (SHR-Salt) for 8 weeks. Isolated coronary segments were subjected to concentration-response curves to acetylcholine (ACh) in the presence or absence of L-NAME (100 μmol), enalaprilate (10 μM), losartan (10 μM), and spironolactone (100 μM). Salt intake did not increase blood pressure in old SHRs, but caused ventricular hypertrophy. The endothelium-dependent relaxation in SHRs was lower than in Wistar rats. However, salt intake did not add further impairment. Both enalaprilate and losartan reduced the vasodilator response in coronary arteries from Wistar, but did not affect SHR-salt rats. Conversely, losartan attenuated the impaired ACh relaxation observed in SHR. Spironolactone reduced the relaxation induced by ACh in coronary arteries from Wistar rats but not in SHR. The renin-angiotensin-aldosterone system participates in the impaired coronary relaxation in aged SHR, but does not participate in deleterious effects under increased salt intake, indicating that age could differentiate the effects of high sodium intake in coronary arteries of SHR.
  Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 04/2013;
• Article: Fas Receptor-deficient lpr Mice are protected against Acetaminophen Hepatotoxicity due to Higher Glutathione Synthesis and Enhanced Detoxification of Oxidant Stress.

  C David Williams, Mitchell R McGill, Anwar Farhood, Hartmut Jaeschke
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  ABSTRACT: Acetaminophen (APAP) overdose is a classical model of hepatocellular necrosis; however, the involvement of the Fas receptor in the pathophysiology remains controversial. Fas receptor-deficient (lpr) and C57BL/6 mice were treated with APAP to compare the mechanisms of hepatotoxicity. Lpr mice were partially protected against APAP hepatotoxicity as indicated by reduced plasma ALT and GDH levels and liver necrosis. Hepatic Cyp2e1 protein, adduct formation and hepatic glutathione (GSH) depletion were similar, demonstrating equivalent reactive metabolite generation. There was no difference in cytokine formation or hepatic neutrophil recruitment. Interestingly, hepatic GSH recovered faster in lpr mice than in wild type animals resulting in enhanced detoxification of reactive oxygen species. Driving the increased GSH levels, mRNA induction and protein expression of glutamate-cysteine ligase (gclc) were higher in lpr mice. Inducible nitric oxide synthase (iNOS) mRNA and protein levels at 6h were significantly lower in lpr mice, which correlated with reduced nitrotyrosine staining. Heat shock protein 70 (Hsp70) mRNA levels were substantially higher in lpr mice after APAP. Conclusion: Our data suggest that the faster recovery of hepatic GSH levels during oxidant stress and peroxynitrite formation, reduced iNOS expression and enhanced induction of Hsp70 attenuated the susceptibility to APAP-induced cell death in lpr mice.
  Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 04/2013;
• Article: Oxidative damage induced by chlorpyrifos in the hepatic and renal tissue of Kunming mice and the antioxidant role of vitamin E.

  Ping Ma, Yang Wu, Qiang Zeng, Yaping Gan, Jiaoe Chen, Xin Ye, Xu Yang
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  ABSTRACT: Chlorpyrifos is a broad-spectrum, chlorinated organophosphate pesticide employed for pest control in various agricultural and animal husbandries. Acute and chronic exposure to CPF can elicit several adverse effects, including oxidative stress. We investigated neurotoxicity of CPF-treated mice, and evaluated the antioxidant effect of vitamin E against oxidative stress and histological changes in the livers and kidneys of CPF-treated mice. Kunming mice were divided randomly into five exposure groups of six: (A) peanut oil; (B) 3 mg/kg CPF; (C) 6 mg/kg CPF; (D) 12 mg/kg CPF; (E) vitamin E (100 mg/kg), 3 h after administration of CPF (12 mg/kg) and used as a post-treatment group. Oral administration of high-dose groups (12 mg/kg) CPF led to a significant increase in levels of reactive oxygen species, DNA-protein crosslinks, 8-hydroxy-2-deoxyguanosine and malondialdehyde, decreases in acetylcholinesterase activity and glutathione level, as well as causing hepatic and renal histopathological change. Except for AChE activity levels, administration of vitamin E to CPF-treated mice restored these biochemical parameters to within normal levels, and resulted in overall improvement in damage to livers and kidneys. These data suggest that oxidative stress is involved in CPF-induced toxicity and that vitamin E can protect against the tissue damage induced by CPF.
  Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 04/2013;
• Article: Intramuscular Responses with Muscle Damaging Exercise and the Interplay Between Multiple Intracellular Networks: A Human Perspective.

  Chad M Kerksick, Darryn Willoughby, Demetrios Kouretas, Aristides Tsatsakis
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  ABSTRACT: Damaging exercise invokes a series of widespread changes that impact many aspects of skeletal muscle physiology. When examining candidate intramuscular mechanisms, those associated with oxidative stress, inflammation, proteolysis and apoptosis appear to have garnered the most interest in the literature, but many aspects of these pathways remain in question. Due to the vast integrated network of signaling activities as well as the many known areas (and likely many unknown areas) of crosstalk throughout these mechanisms, in vivo research can be challenging. Currently, a relatively small number of studies have examined time-course related changes to blood-based markers of oxidative stress and even fewer have examined intramuscular changes using in vivo models. An equally small number of studies have examined intramuscular changes in apoptotic activity. While changes in other tissues hold importance, intramuscular adaptations and the mechanisms involved are of the highest importance for determining how skeletal muscle adapts and respond to stressful, damaging stimuli.
  Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 04/2013;
• Article: Inhibition of TGF-β1 /Smad signal pathway is involved in the effect of Cordyceps sinensis against renal fibrosis in 5/6 nephrectomy rats.

  Ming-Ming Pan, Ming-Hui Zhang, Hai-Feng Ni, Jun-Feng Chen, Min Xu, Aled Owain Phillips, Bi-Cheng Liu
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  ABSTRACT: The present study aimed to investigate the effects of Cordyceps sinensis on renal fibrosis and its possible mechanisms. Sprague-Dawley rats were randomly divided into three groups: sham operation (SHAM) group, 5/6 subtotal nephrectomy (SNx) untreated group, and 5/6 subtotal nephrectomy treated with Cordyceps sinensis (2.0g/kg.d) (CS) group. Rats were studied 12 weeks after the surgery, and the CS group presented with significantly lower proteinuria, and better renal function compared with the SNx group (p<0.05). Pathological study showed that the glomerulosclerosis tubulointerstitial injury score was significantly reduced in the CS group compared with the SNx group. Furthermore, the mRNA expression of TGF-β1, Smad2 and Smad3 and the protein expression of TGF-β1, TβRI, TβRII and p-Smad2/3 were attenuated by the Cordyceps sinensis treatment. In constrast, the mRNA and protein expression of Smad7 was upregulated. Furthermore, the expression of α-SMA and FSP1 was also significantly attenuated, accompanied by the increasing expression of E-cadherin, suggesting the inhibition of the epithelial-mesenchymal transition (EMT). In conclusion: Cordyceps sinensis exerted its antifibrotic effect on the SNx rats through the inhibition of the TGF-β1/Smad pathway.
  Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 04/2013;
• Article: 12 weekś aerobic and resistance training without dietary intervention did not influence oxidative stress but aerobic training decreased atherogenic index in middle-aged men with impaired glucose regulation.

  Mika Venojärvi, Ayhan Korkmaz, Niko Wasenius, Sirpa Manderoos, Olli J Heinonen, Harri Lindholm, Sirkka Aunola, Johan G Eriksson, Mustafa Atalay
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  ABSTRACT: Our aim was to determine whether 12 weekś aerobic Nordic walking (NW) or resistance exercise training (RT) without diet-induced weight loss could decrease oxidative stress and atherogenic index of plasma (AIP), prevalence of metabolic syndrome (MetS) and MetS score in middle-aged men with impaired glucose regulation (IGR) (n =144. 54.5 ± 6.5 years). In addition, we compared effects of intervention between overweight and obese subgroups. Prevalence of MetS and AIP index decreased only in NW group and MetS score in both NW and RT groups but not in control group. The changes in AIP index correlated inversely with changes in plasma antioxidant capacity. The change in AIP index remained a significant independent predictor of the changes in MetS score after the model was adjusted for age, BMI and volume of exercise (MET h/wk) in NW group. There were no changes in the other measured markers of oxidative stress and related cytokines (e.g. osteopontin and osteoprotegerin) in any of the groups. Nordic walking decreased prevalence of MetS and MetS score. Improved lipid profile remained a predictor of decreased MetS score only in NW group and it seems that Nordic walking has more beneficial effects on cardiovascular disease risks than RT training.
  Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 04/2013;
• Article: Paeoniflorin Protects Against ANIT-Induced Cholestasis by Ameliorating Oxidative Stress in Rats.

  Yanling Zhao, Guangde Zhou, Jiabo Wang, Lei Jia, Ping Zhang, Ruisheng Li, Limei Shan, Bing Liu, Xueai Song, Shijing Liu, Xiaohe Xiao
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  ABSTRACT: Paeoniflorin, one of the primary bioactive components in Chi shao, are widely used in traditional Chinese medicine. A lot of evidences suggest that Paeoniflorin has potential anti-oxidant effects. However, whether Paeoniflorin plays roles in cholestasis is unclear. In this study, we examined the protective effect of Paeoniforin against alpha-naphthylisothicaynate (ANIT)-induced cholestasis in rats. Our data demonstrated that the high (0.2 g/kg body weight) and medium (0.1g/kg body weight) doses of Paeoniflorin significantly prevented ANIT-induced changes in bile flow and the serum levels of total bilirubin, direct bilirubin, total bile acid,γ-glutamyltranspeptidase, glutamate-pyruvate transaminase, glutamate-oxaloacetic transaminase and alkaline phosphatase. Moreover, we also found that Paeoniflorin significantly inhibited nitric oxide and malondialdehyde production, and restored glutathione decrease induced by ANIT. EPR data further indicated that Paeoniflorin inhibited ANIT-mediated reactive oxygen species (ROS) production. The overexpression of NADPH oxidase 4 induced by ANIT were significantly reversed when treated with Paeoniflorin, suggesting that Paeoniflorin could scavenge ROS via inhibiting NADPH oxidase 4 expression. Paeoniflorin treatment could also relieve ANIT-induced liver pathological injuries as indicated by histological assay. These findings indicate that Paeoniflorin exerts a dose-dependent protective effect on ANIT-induced cholestatic liver injury in rats, and the mechanism of this activity is related to its attenuation of oxidative stress in liver tissue.
  Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 04/2013;
• Article: Protective effects of Keemun black tea polysaccharides on acute carbon tetrachloride-caused oxidative hepatotoxicity in mice.

  Yanfei Sun, Xingbin Yang, Xinshan Lu, Dongying Wang, Yan Zhao
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  ABSTRACT: This study was designed to investigate chemical characterization of the water-soluble polysaccharides extracted from Keemun black tea (KBTP), and their antioxidant and hepatoprotective effects against CCl4-induced oxidative damage in mice. HPLC analysis revealed that KBTP is the typical acidic heteropolysaccharides and consisted of nine monosaccharides. Furthermore, KBTP showed highly ferric-reducing antioxidant power and scavenging effects against DPPH(•), OH(•) and O2(•-) in vitro. Administration of KBTP (200, 400 and 800 mg/kg·bw) in mice ahead of CCl4 injection could observably antagonize the CCl4-induced increases in serum ALT, AST, TG and TC, and the hepatic MDA and 8-iso-PGF2a levels, respectively. Mice with KBTP pretreatment displayed a better profile of hepatosomatic index and the improved GSH and SOD activities in comparison with CCl4-intoxicated mice. These biochemical results were further supported with liver histopathological assessment, revealing that KBTP has an observable prevention of liver damage induced by CCl4 in mice.
  Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 04/2013;