Early diagnosis of kidney injuries caused by herbs is necessary to enable effective treatments, prevent kidney failure and promote the internationalization and modernization of herbal medicine. Whereas the toxic assessment evidence has not integrated yet, and the evaluation method has not been unanimously agreed. For example, the gold standard assessing toxicity in animals remains to be histopathology, but serum biochemical indexes are the primary measures for monitoring organs dysfunction in humans. In this study, using Sprague Dawley rats, we investigated whether integrated analyses of transcriptomic and metabolomic data with toxicological evidence chain (TEC) concept could identify indicators of injury and provide new insights into the mechanisms of nephrotoxicity. Firstly, the objective phenotype of the animals was observed in detail and the toxicity performance was collected after administration. Subsequently, histopathological examination and serum biochemical toxicity evidence were collected. Next, we obtained concurrent measurements of transcriptomic changes in kidneys, and changes along with metabolic profiles in serum, after exposure to PT(Podophyllotoxin) to acquire evidence at the molecular level. Last but not least, the GTEA (Grades of Toxicological Evidence Assessment) based on GRADE(Grading of Recommendations Assessment, Development, and Evaluation) system was used to evaluate toxic evidence which can be assigned to a toxic level. The orally gavaged rats with PT have been confirmed with dose-dependent kidney damage from 5 to 15 mg/kg after 4 d. Our findings suggest that the main pathological changes occurred in Glycerophosphatidylcholine metabolism, Arachidonic acid metabolism, Energy metabolism, Tyrosine metabolism, Tryptophan metabolism and so on.Moreover, the alteration of the potential metabolites lipid (i.e. LPC, palmitic acid) and sulfate could serve as plausible markers of PT-induced kidney injury. Our approach provides a mechanistic framework for the refinement of the grading standard of toxicity evidence, which is applicable to other toxicants originated from herbal medicine based on multi-omics data.

Cold atmospheric plasmas (CAPs) used in plasma medicine have shown great potential in various aspects including wound healing, dermatology, cancer therapy, etc. It is one of the important issues to determine the plasma dosage in plasma medicine because it dominates the specific plasma treatment results. However, the multi-process interactions between CAPs and biological materials make it rather challenging to give an accurate and versatile definition for plasma dosage. In this study, the ratio of the discharge energy to the number of the treated in vitro kidney cells (mJ/cell) was employed as the unit of the plasma dosage. Additionally, inspired by basic knowledge of pharmacy, the median lethal dose (LD₅₀) was employed to help estimate the plasma dosage. The experimental results show that the value of LD₅₀ using the newly designed CAP Bio-Med Platform for the kidney cells is 34.67 mJ/cell. This biology-based method has the advantages of easy operation, independence of specific CAP sources, and also independence of complex interactions between CAPs and the treated biological targets, and consequently, may provide a new direction to quantitatively define the plasma dosage in various plasma medical applications.