Effect of Tebuconazole exposure on oral Atenolol absorption in rats,based on bile acid homeostasis

Objective:This study is aimed to explore the effect of triazole fungicide tebuconazole(TEB)exposure on the oral absorption behavior of atenolol(AT),based on the homeostasis of bile acids(BAs).Methods:TEB was daily gavaged to rats with 3 mg/kg dose for 28 days to establish the TEB-exposure rat model.The amounts of glycocholic acid,glycochenodeoxycholic acid,taurocholic acid and taurine deoxycholic acid in the small intestine contents of normal and TEB-exposure rats were detected by LC-MS/MS.AT(10 mg/kg)were gavaged to the normal and TEB-exposure rats,and then blood were collected from orbital venous plexus at predetermined time-points.The concentration of AT in plasma was detected by LC-MS/MS,and the pharmacokinetic parameters were calculated by the DAS pharmacokinetic software.An intestinal circulation perfusion model was established in normal rats,and perfused with the perfusates containing the model drug of fluorescein and the BAs with the same compositions as the normal/TEB-exposure rats.After perfusion,the absorption and permeability of fluorescein in intestine were detected,as well as the oxidative stress status and ZO-1 expression level in the intestinal tissues.Results:Compared with normal rats,TEB-exposure increased the amounts of glycocholic acid,glycochenodeoxycholic acid,taurocholic acid and taurine deoxycholic acid in intestine significantly(P<0.001).In TEB-exposure rats,the maximum plasma concentration and area under the curve of AT were increased significantly than those of normal rats(P<0.05),and the peak time was significantly delayed(P<0.05).The TEB-induced BAs homeostasis perturbance increased intestinal permeability,and this effect was associated with the elevation of oxidative stress and the down-regulation of intercellular tight junction proteins in intestinal tissues.Conclusion:TEB-exposure can affect the oral absorption behavior of AT,which is probably related with the intestinal BAs homeostasis perturbance,thus it might affect the clinical efficacy and safety of this drug.

Inhibitory Effects of Phenamacril, Tebuconazole and Their Mixtures on Fusarium graminearum in Wheat

Fusarium head blight caused by Fusarium graminearum is one of the most serious diseases in wheat production worldwide, which seriously affects the yield and quality of wheat. Wheat grains carrying the pathogen are poisonous to human and livestock health. With the long-term use of single chemical pesticide, the drug-resistance of F. graminearum is increasing day by day, and mixed agent is one of the effective strategies to improve the efficacy and delay the resistance. The mycelial growth rate method was used to determine the inhibition rates of phenamacril, tebuconazole and their mixtures(1∶1, 1∶3, 1∶5, 1∶7, 3∶1, 5∶1 and 7∶1). The synergistic coefficient(SR) was calculated by Wadley method, and the combined action types of the two agents were evaluated. The results showed that the EC_(50) of tebuconazole was 0.418 28 mg/L, and that of phenamacril was 0.489 8 mg/L; the optimum mixture ratio of phenamacril and tebuconazole was 1 ∶1, with the EC_(50) value of 0.053 74 and the synergistic coefficient of 4.2696, and the control effect of mixed agent was significantly better than that of single agent. It is feasible to control Fusarium head blight by mixing phenamacril and tebuconazole, providing a theoretical basis for development of new compound agents and effective control of Fusarium head blight.

Inhibition Effect and Synergistic Effect of Prochloraz and Tebuconazole and Their Mixture on Fusarium graminearum

Wheat scab caused by Fusarium graminearum is increasingly severe in the middle and lower reaches of the Yangtze River region. With long-term use of single chemical pesticide,the drug resistance of F. graminearum is growing day by day. In order to reveal the inhibition effect and synergistic effect of prochloraz and tebuconazole and their mixture on F. graminearum,new compound agents for controlling wheat scab were developed. The inhibition effect and synergistic effect of prochloraz and tebuconazole mixed at seven different ratios on F. graminearum were studied. The results showed that the efficiency of the mixture was the best when the proportion of prochloraz and tebuconazole was 1:7; the EC50 was 0.145 36 and the synergistic coefficient was 1.853 9. The results provide a theoretical basis for development of new compound agents and effective control of wheat scab.

Determination of Tebuconazole Residue in Apples and Vegetables by Matrix Solid Phase Dispersion-Gas Chromatography

[ Objective] The study aimed to determine tebuconazole residue in apples and vegetables using matrix solid phase dispersion-gas chro- matography （MSPD-GC）. [ Method] The effects of extraction and determination conditions on the detection of tebuconazole left in apples and veg- etables were analyzed, and the optimum extraction conditions were determined. [ Result] The recovery rate of tebucenazole was the highest when the ratio of a sample to florisil dispersant was 1 ： 4, and the mixture of hexane and acetone （ 1 ： 1 ） with total volume of 8 ml was as the eluant. Under the optimum conditions, the relative standard deviation （RSD） of the method was 4.9% -7.6%, and the detection limit was 0.1 tJg/g, while the re- covery rate of tebuconazole changed from 86.7% to 95. 2% . [ Conclusion] The method was simple, accurate, sensitive and applicable to the de- termination of tebuconazole in aaricultural Droducts.

Application Technology of Tebuconazole WG against Sheath Blight 75% Trifloxystrobin · Rice Blast and Rice

[ Objective] The paper was to confirm the best application period and frequency of 75% trifloxystrobin ·tebuconazole WG against rice blast and rice sheath blight. [ Method] Influences of different dosages and different application periods of 75% trifloxystrobin · tebuconazole WG on control effects against rice blast and rice sheath blight, as well as their effects on rice yields were studied in the paper. [Result] The control effects of three different fungicides application treatments against rice sheath blight were 80.24%, 83.0% and 67.99%, and the control effects against rice blast were 56.4%, 49.11% and 61.1%, respective- ly. Advanced application of fungicide for two times had good prevention effect against rice sheath blight ; properly delayed application of fungicides for two times was conducive to improving the control effect against rice blast, and one time application of sufficient fungicide during middle booting stage had higher control effect than application for two times. Effective panicle number per unit area, total grain number, 1 000-grain weight and moisture content of various fungicide application treat- ments did not have significant difference with those of the treatments without fungicide application, but grain number per panicle in treatments applied with fungicide was higher than the treatment without application. [ Conclusion] 75% Trifloxystrobin ·tebuconazole WG has better control effect on rice blast and sheath blight, which helps to promote the formation of rice grain and increases yield significantly. The fungicide application against rice sheath blight should be appropriately ad- vanced, and application for one time against panicle blast after middle booting stage is helpful to improve the control effect.

Cardiac energy metabolism disorder mediated by energy substrate imbalance and mitochondrial damage upon tebuconazole exposure

Tebuconazole exposure has been described as an increasing hazard to human health.An increasing number of recent studies have shown a positive association between tebuconazole exposure and cardiovascular disease risk,which is characterized by the reduction of adenosine triphosphate(ATP)synthesis.However,researches on the damage of tebuconazole exposure to energy metabolism and the related molecular mechanisms are limited.In the present study,male C57BL/6 mice were treated with tebuconazole at different low concentrations for 4 weeks.The results indicated that tebuconazole could accumulate in the heart and further induce the decrease of ATP content in the mouse heart.Importantly,tebuconazole induced an obvious shift in substrate utilization of fatty acid and glucose by disrupting their corresponding transporters(GLUT1,GLUT4,CD36,FABP3 and FATP1)expression,and significantly repressed the expression of mitochondrial biogenesis(Gabpa and Tfam)and oxidative phosphorylation(CS,Ndufa4,Sdhb,Cox5a and Atp5b)related genes in a dosedependent manner.Further investigation revealed that these alterations were related to the IRS1/AKT and PPARγ/RXRαpathways.These findings contribute to a better understanding of triazole fungicide-induced cardiovascular disease by revealing the key indicators associated with this phenomenon.

Enantioseletive bioaccumulation of tebuconazole in earthworm Eisenia fetida

Methods of extraction and determination of tebuconazole enantiomers in earthworm （Eisenia fetida） were developed by capillary electrophoresis （CE） and high performance liquid chromatography （HPLC）. Both CE and HPLC have excellent resolution and recovery. The linearity ranges were 2.9-102.4 mg/kg and 3.0-99.6 mg/kg for （＋）-R-tebuconazole and （-）-S-tebuconazole respectively in CE, and from 0.56 to 1000 mg/kg for both enantiomers in HPLC. Enantioselective bioaccumulation in earthworms from soft was investigated under laboratory condition at concentrations of 10 and 50 mg/kg dw in soil. The uptake kinetics of （＋）-R-tebuconazole fitted the first- order kinetics well with r2 0.97 and 0.94 under 10 and 50 mg/kg dw exposure condition, respectively, while （-）-S-tebuconazole with r2 0.75 and 0.22 did not show the same. Bioaccumulation of tebuconazole in earthworm tissues was enantioselective with a preferential accumulation of （＋）-R-tebuconazole. The （＋）-R-tebuconazole might also have biomagnifying effect potential in earthworm food chain with biota-sediment accumulation factor （BSAF） of 1.64 kg OC/kg lip in 10 mg/kg dw exposure group and 2.61 kg OC/kg lip in 50 mg/kg dw exposure group from soil to earthworm after 36 days. Although （-）-S-tebuconazole shares the same physicochemical properties with （＋）-R-tebuconazole, it did not biomaguify. BSAFs of （-）-S-tebuconazole were 0.50 kg OC/kg lip （10 mg/kg dw tebuconazole exposure） and 0.28 kg OC/kg lip （50 mg/kg dw tebuconazole exposure） after 36 days, which was possibly owing to biotransformation or metabolism in earthworm tissues.

Fixation Property of Copper Triazole Wood Preservatives

According to AWPA E11-2006 standard,copper fixation rates of several copper-based formulations,such as ammoniacal copper,amine copper,and ammoniacal-ethanolamine copper,as well as alkaline copper quaternary(ACQ),were tested and compared in this paper.And the fixation rates of tebuconazole(TEB) and propiconazole(PPZ) in several formulations,such as copper azole,emulsified type and solvent type,were also compared.The determination of copper content in the leachate was analyzed by atomic absorption spectrom...