In vitro assessment of corticosteroid effects of eight chiral herbicides

Abstract

Information regarding the enantioselective endocrine disruption of chiral herbicides is scarce. This study assessed the disrupting effects of eight typical chiral herbicides on corticosteroids (including glucocorticoids and mineralocorticoids). Enantioselectivity of eight chiral herbicides were evaluated for their agonistic/antagonistic effects on glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) with CHOK1 cell line using reporter gene assay. Their influence on the production of corticosteroids were further investigated in H295R cell line using enzyme-linked immunosorbent assay (ELISA). None of the racemates or enantiomers of eight chiral herbicides exhibited GR or MR agonistic activity at non-cytotoxic concentrations. However, rac-propisochlor and S-imazamox antagonized cortisol-induced transactivation of GR by 21.79% and 38.73% at the concentration of 1.0 × 10⁻⁷ M and 1.0 × 10⁻⁶ M, respectively, and R-napropamide remarkably attenuated aldosterone-induced MR transactivation by 68.78% at 1.0 × 10⁻⁶ M. The secretion of cortisol was significantly restrained after treated with 1.0 × 10⁻⁶ M rac-propisochlor and rac-/R-napropamide at the concentration of 1.0 × 10⁻⁶ M by 26.49%, 30.10% and 35.27%, respectively, while this glucocorticoid was remarkably induced by 1.0 × 10⁻⁵ M rac-diclofop-methyl and its two enantiomers at the concentration of 1.0 × 10⁻⁵ M by 75.60%, 100.1% and 68.78%, respectively. Exposure to rac-propisochlor (1.0 × 10⁻⁶ M), S-diclofop-methyl (1.0 × 10⁻⁵ M) or rac-/S-/R- acetochlor (1.0 × 10⁻⁶ M) and rac-/S-/R-lactofen (1.0 × 10⁻⁶ M) inhibited the secretion of aldosterone by approximately 40%. Our findings suggested that chiral herbicides disrupted corticosteroid homeostasis in an enantioselective way. Therefore, more comprehensive screening is required to better understand the ecological and health risks of chiral pesticides.

Keywords:

• Enantioselectivity
• chirality
• endocrine disruption
• glucocorticoid receptor
• mineralocorticoid receptor
• CHO cells
• H295R cells

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the Fundamental Research Funds for the Central Universities (2019FZJD007 and 2019QNA6008), National Natural Science Foundation of China (21876151), and Zhejiang University K. P. Chao’s High Technology Development Foundation.