General toxicity of Pinellia ternata (Thunb.) Berit. in rat: a metabonomic method for profiling of serum metabolic changes

Abstract

Ethnopharmacological relevance: BX is a traditional Chinese medicine (TCM) from the plant Pinellia ternata(Thunb.) Berit. It has been traditionally used to treat cough, vomiting, infection and inflammation. Despite of its potentially clinical utility, it also has many side effects and toxicity.

Aim of the study: We propose here an ultra performance liquid chromatography coupled with quadrupole time-of-fight mass spectrometry (UPLC Q-TOF/MS) metabonomics approach to elucidate the toxicity in rats induced by orally administered BX in multiple organs including the kidney, liver, and heart.

Materials and methods: Serum samples were collected from Sprague-Dawley male rats exposed to BX (6g/kg/day, n=10) and healthy controls (n=10) at the 48 h, 144 h, 240 h, and 336 h postdose for LC/MS analyses. Through principal component analysis and orthogonal partial least squares-discriminant analysis of the integrated serum MS data, we distinguished the BX group from the healthy control group and identified the differential metabolites and pertinent altered biological pathways in response to the herbal toxin. The liver, kidney, heart were assessed using conventional histopathological examinations at the end point of the experiment. The serum samples at the 336 h postdose were assessed using biochemistry test.

Results: Significant differences in the serum levels of phospholipids, amino acids, L-carnitine and L-acetylcarnitine were observed in BX-induced rats, indicating the perturbations of phospholipid metabolism, amino acid metabolism and carnitine metabolism in BX-induced rats.

Conclusions: In the paper, we used metabonomics approach to study the toxicity of BX for the first time. With blood biochemistry, histopathological examinations and metabonomics methods, we validated that oral administration of crude BX caused no obvious liver and kidney toxicity in SD rats. BX may possess certain cardio toxicity in SD rats. The metabolism changes suggested that metabonomic approach was a promising tool to study and diagnose TCM-induced toxicity.

Keywords: Metabonomics; Pinellia ternata (Thunb.) Berit; Serum; Toxicity; UPLC–MS.