Incompatibility assessment of Genkwa Flos and Glycyrrhizae Radix et Rhizoma with biochemical, histopathological and metabonomic approach.

ETHNOPHARMACOLOGICAL RELEVANCE: As recorded in traditional Chinese medicine (TCM) theory, Genkwa Flos (YH) and Glycyrrhizae Radix et Rhizoma (GC) compose one herbal pair of the so-called "eighteen incompatible medicaments", which indicate pairs of herbs that are mutually incompatible and that theoretically should not be applied simultaneously. However, the theory has been called into question due to a lack of evidence. AIMS OF STUDY: In this study, the incompatibility of YH and GC was investigated based on an assessment of the toxic effects of their combination by traditional safety methods and a modern metabonomic approach. MATERIALS AND METHODS: Sprague-Dawley rats were used to evaluate the subacute toxicity of YH and YH-GC. The serum, urine, and several tissues were collected for biochemical analysis, histopathological examination, and metabonomic analysis. RESULTS: Rats exposed to a dose of 1.0 g/kg YH (3 times of the Chinese Pharmacopoeia maximum dose) exhibited toxicity of the heart, liver, kidney and testes, and rats exposed to a YH-GC combination (1.0 g/kg YH + 1.0 g/kg GC) exhibited similar hepatotoxicity, which aggravated renal and reproductive toxicity. Following this, a metabonomic study tentatively identified 14 potential biomarkers in the YH group and 10 potential biomarkers in the YH-GC group, and metabolic pathways were then constructed. YH disturbed the pathways of glycerophospholipid metabolism, primary bile acid biosynthesis, and sphingolipid metabolism, while YH-GC combination induced disruptions in phenylalanine, tyrosine and tryptophan biosynthesis, tyrosine metabolism, and glycerophospholipid metabolism. CONCLUSION: The toxicities of YH and YH-GC combination above the Chinese Pharmacopoeia dose were obvious but different. Metabonomics combined with biochemical and histopathological methods can be applied to elucidate the toxicity mechanism of the YH-GC combination that caused liver, kidney and reproductive injuries in rats.

Development and clinical application of a length-adjustable water phantom for total body irradiation.

A new type of water phantom which would be specialised for the absorbed dose measurement in total body irradiation (TBI) treatment is developed. Ten millimetres of thick Plexiglas plates were arranged to form a square cube with 300 mm of edge length. An appropriate sleeve-type piston was installed on the side wall, and a tabular Plexiglas piston was positioned inside the sleeve. By pushing and pulling the piston, the length of the self-made water phantom could be varied to meet the required patients' physical sizes. To compare the international standard water phantom with the length-adjustable and the Plexiglas phantoms, absorbed dose for 6-MV X ray was measured by an ionisation chamber at different depths in three kinds of phantoms. In 70 cases with TBI, midplane doses were metered using the length-adjustable and the Plexiglas phantoms for simulating human dimensions, and dose validation was synchronously carried out. There were no significant statistical differences, p > 0.05, through statistical processing of data from the international standard water phantom and the self-designed one. There were significant statistical differences, p < 0.05, between the two sets of data from the standard and the Plexiglas one. In addition, the absolute difference had a positive correlation with the varied depth of the detector in the Plexiglas phantom. Comparing the data of clinical treatment, the differences were all <1 % among the prescription doses and the validation data collected from the self-design water phantom. However, the differences collected from the Plexiglas phantom were increasing gradually from +0.77 to +2.30 % along with increasing body width. Obviously, the difference had a positive correlation with the body width. The results proved that the new length-adjustable water phantom is more accurate for simulating human dimensions than Plexiglas phantom.