Acute study and the absorption, distribution, and metabolomic profile of the natural compound propyl-propane-thiosulfonate from allium in rats

Abstract

Propyl-propane thiosulfonate (PTSO) is an organosulfur compound found in Allium spp., commonly used in animal nutrition and various agri-food applications. Extensive studies have demonstrated the safety of PTSO for feed use, including investigations into genotoxicity, mutagenicity, and subchronic toxicity in rats. However no kinetic or metabolic study has been previously performed. This study aimed to conduct an in vivo toxicokinetic assessment of PTSO in rats. For this purpose, eighteen Sprague Dawley rats received an oral dose of 175 mg/kg via gastric gavage. Plasma and tissue samples (brain, stomach, liver, lung, kidney, spleen, and testicle) were collected at specific intervals (10 min, 20 min, 30 min, 1h, 2h, 4h, 6h, 8h, and 24h) and analyzed using Gas Chromatography-High-Resolution Mass Spectrometry, Pyrolysis Gas Chromatography -High-Resolution Mass Spectrometry, and Ultra-High Performance Liquid Chromatography-Tandem Mass Spectrometry to detect PTSO and its metabolites. PTSO was not detected in plasma or solid tissues throughout the sampling period; however, phase I and phase II metabolites were identified in both matrices. The toxicokinetic profile of s-propyl mercaptocysteine (CSSP), a significant metabolite, exhibited a well-correlated model. In the stomach, CSSP reached peak concentrations of 495.63 ± 6.53 ng/mL, while lower concentrations of 123.59 ± 8.35 ng/mL were observed in plasma. Furthermore, CSSP demonstrated high water solubility and rapid excretion, with a plasma half-life of 0.66 ± 0.05 h. Overall, these findings substantiate the safety profile of PTSO for specific agri-food applications under the conditions investigated.