Stereoselective metabolism and toxicity of the herbicide fluroxypyr methylheptyl ester in rat hepatocytes

Abstract

We investigated the stereoselective degradation kinetics and toxicity of fluroxypyr methylheptyl ester (FPMH) in rat hepatocytes using a chiral high-performance liquid chromatographic method. The T1/2 of (−)-FPMH was about two times longer than that of (+)-FPMH after the rat hepatocytes were incubated with 10, 20, and 50 μM of rac-FPMH. There was no chiral conversion or transformation during their incubation with the hepatocytes. Toxicity differences were observed among the two enantiomers of FPMH and fluroxypyr (FP) in their EC50 values in rat hepatocytes. Of all the tested compounds, FP was most toxic to the rat hepatocytes. The (−)-FPMH enantiomer showed higher toxicity than the (+)-FPMH, whereas the racemic mixture displayed intermediate toxicity. The data presented here are important for a more thorough understanding of this pesticide and should be useful for its full environmental assessment.

Applicability of the Rayleigh equation for enantioselective metabolism of chiral xenobiotics by microsomes, hepatocytes and in-vivo retention in rabbit tissues

“…Two more test cases are reported by Xu et al . studying the stereoselective metabolism of the chiral herbicides ethofumesate (ETO) 53 and fluroxypyr methylheptyl ester (FPMH) 54 using hepatocytes from male Sprague-Dawley rats. In both cases the author provided the first order half-life values as 2.0 h and 4.1 h and 5.1 min and 13.1 min for (+) and (−) ETO and FPMH, respectively.…”

Stereoselective Toxicity and Metabolism of Lactofen in Primary Hepatocytes From Rat

“…Hepatocytes in chemically defined culture conditions express most typical hepatic biochemical functions, among which is the ability to metabolize drugs . Hepatocytes isolated from animals are of great value in short‐term predictive assays to establish routes of metabolism and the mechanisms of toxicity of veterinary, pharmaceutical, and agrochemical compounds …”

“…18 Hepatocytes isolated from animals are of great value in shortterm predictive assays to establish routes of metabolism and the mechanisms of toxicity of veterinary, pharmaceutical, and agrochemical compounds. 19 Therefore, primary rat hepatocytes were used as the model to evaluate the stereoselective metabolism of lactofen, as well as biodegradation of two of its major metabolites, acifluorfen and desethyl lactofen, in the present study. In addition, for a more comprehensive assessment of metabolic behavior of lactofen, cytotoxicity of the parent compounds (rac-lactofen, S-(+)-and R-(À)-lactofen) and the metabolites (acifluorfen, S-(+)-and R-(À)-desethyl lactofen) of rat hepatocytes were assessed via the methyl tetrazolium (MTT) assay.…”

Enantioselective Metabolism and Interference on Tryptophan Metabolism of Myclobutanil in Rat Hepatocytes

“…Among which, hepatocytes are recognized as the closest model to liver because in chemically defined culture conditions they express the most typical hepatic biochemical functions and satisfy the need of studying the effect on the endogenous and exogenous metabolisms at the same time. For short‐term predictive assays, hepatocytes are of great value to establish routes of metabolism and to explore the mechanisms of toxicity of foreign compounds …”

“…For short-term predictive assays, hepatocytes are of great value to establish routes of metabolism and to explore the mechanisms of toxicity of foreign compounds. 17 A combined analysis of the endogenous and the exogenous metabolisms will make the mechanism by which the responses of an organism to a perturbation occur more clear. Therefore, primary rat hepatocytes were used as the model to evaluate the enantioselective metabolism of exogenous myclobutanil.…”