Stereoselective metabolism, distribution, and bioaccumulation brof triadimefon and triadimenol in lizards

Abstract

a b s t r a c tIn this research, Chinese lizards (Eremias argus) were chosen as laboratory animal to evaluate the stereoselectivity in the processes of metabolism, distribution, and bioaccumulation of triadimefon. A validated chiral high-performance liquid chromatography coupled with triple quadruple mass spectrometry (HPLC-MS/MS) method was developed for determining enantiomers' residues of parent compound triadimefon and its metabolite triadimenol in lizard blood and tissues. Pharmacokinetic results of single-does exposure suggested that S-(þ )-triadimefon was metabolized easier than R-( À )-triadimefon, and RR-(þ )-triadimenol was the main metabolic product of triadimefon. During the continuous exposure of two dose (40 mg/kg bw Á d and 200 mg/kg bw Á d), enantiomers of triadimefon and triadimenol were detected in all body compartments, with the highest triadimefon concentrations in brain. However, the triadimenol concentrations were not significantly different among the compartments. The concentrations of RS-( þ)-triadimenol were negative correlated with concentrations of RR-(þ )-triadimenol both in blood (r¼ À0.775, p¼0.024) and liver (r¼ À0.834, p¼0.02) in 200 mg/kg bw Á d group, which indicates that chiral conversion between enantiomers of triadimenol might exist in the metabolic process of triadimefon. In all the processes, the enantiomer fractions (EFs) of R-(À )-triadimefon and RR-(þ )-triadimenol were significantly different from their natural ratios, 0.5 and 0.1, respectively, which proved that metabolism, bioaccumulation, and distribution of triadimefon and triadimenol in lizards were enantioselective. These results help enrich and supplement the knowledge of the stereoselective behaviour of triadimefon and triadimenol in reptile.

Tissue distribution and metabolism of triadimefon and triadimenol enantiomers in Chinese lizards ( Eremias argus )

“…However, C max time in S-(+)-TF (6 h) was faster than that in R-(-)-TF (12 h). Similar results were found in Kenneke et al (2010) on rainbow trout and in Wang et al (2014). Until the end of the experiment (7 days), there was still slight triadimefon residue (Figs.…”

“…To ensure the deglutition of triadimefon by lizards, we pushed the lavage needle very slowly in order to give them enough time to assimilate the pharmaceutical, and kept their mouths closed for a few minutes after dosing. In the previous research, a preliminary experiment at 90 mg/kg bw was conducted which no difference clinical signs were found between the control and treated groups (Wang et al, 2014). So, in present study, the control group was only sacrificed at 168 h. The organs including liver, brain, kidney and fat in each group were weighted and collected in heparinized tubes separately.…”

“…Treated groups were assigned with R-(-)-TF or S-(+)-TF dissolved in corn oil respectively and administered orally at 50 mg/kg bw . Combined avian toxicity test of triadimefon (LD 50 > 2000 mg/kg bw ) published by U.S Environmental Protection Agency (U.S. EPA) (Extoxnet, 2010) and the previous study by Wang et al (2014), 2.5% of the LD 50 was chosen as the dosing concentration. The control group received only corn oil orally and the dosing method was set up in steps (Suski et al, 2008).…”

Synergistic actions between tebuconazole ligand and Cu(ii) cation: reasons for the enhanced antifungal activity of four Cu(ii) complexes based on the fungicide tebuconazole

“…2,3 These compounds inhibit fungal proliferation by inhibiting steroid demethylation. [11][12][13][14][15] Among these complexes, complexation of pesticides with Cu(II) has potential advantages including the enhancement of persistence, longer shelflife, reduction of mammalian toxicity and conversion of nonsystemic to systemic pesticides. [5][6][7] Recently, the complexes, containing transition metal and 1,2,4triazole ligands have been extensively investigated, mainly because of not only their innovative structures [8][9][10] but also their application values and development potential in optical, electrical, various biological properties.…”

Enantioselective metabolism of triadimefon and its chiral metabolite triadimenol in lizards

“…Stereoselective behaviors of TF and TN have been reported in soil microorganisms and rainbow trout (Garrison et al, 2011;Kenneke et al, 2010;Li et al, 2011). In our previous study (Wang et al, 2014), we reported the stereoselective metabolism, distribution and bioaccumulation of TF and TN in lizards under racemic form of TF exposure. These results gave us a preliminary understanding of stereoselective behaviors of TF and TN.…”