Sex-related deposition and metabolism of vanisulfane, a novel vanillin-derived pesticide, in rats and its hepatotoxic and gonadal effects
2022
Shao, Siyao | Cheng, Xi | Zheng, Ruonan | Zhang, Subin | Yu, Zhiyang | Wang, Haiyan | Wang, Wei | Ye, Qingfu
A series of vanillin derivatives have recently been synthesized as effective candidate antiviral agents, with vanisulfane exhibiting pronounced curative and protective activities against cucumber mosaic virus and potato virus Y. However, research on some new pesticides usually ignores their various metabolites and sex-related toxicity. Assisted by ¹⁴C labeling, a trial was conducted to investigate the tissue distribution, excretion, and metabolism of vanisulfane in male and female rats for the first time. The results showed that 83.30–87.51% of applied ¹⁴C activity was excreted in urine and feces within 24 h of oral administration, and ¹⁴C was most abundant in the liver and kidney in both sexes. Interestingly, sex differences were observed in the experiment, with lower body clearance in males than in females 24 h after treatment and preferences for biliary and renal excretion of the pesticide in male and female rats, respectively. A high degradation rate was found for vanisulfane in the plasma; thus, the metabolites of vanisulfane were investigated using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) combined with ¹⁴C labeling. One glucuronic acid conjugate and two oxidation metabolites were detected, supporting the monitoring of vanisulfane in vivo. Additionally, rats exposed to vanisulfane exhibited hepatic steatosis in both sexes, along with mild gonadal effects in males. This research offers an effective method for conducting environmental behavioral research and provides new insights for evaluating the potential risks of novel pesticides in mammals from a sex perspective.
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