Absorption difference between hepatotoxic pyrrolizidine alkaloids and their N-oxides - Mechanism and its potential toxic impact.

ETHNOPHARMACOLOGICAL RELEVANCE: Pyrrolizidine alkaloids (PAs) are a group of phytotoxins widely present in about 3% of flowering plants. Many PA-containing herbal plants can cause liver injury. Our previous studies demonstrated that PA N-oxides are also hepatotoxic, with toxic potency much lower than the corresponding PAs, due to significant differences in their toxicokinetic fates. AIM OF STUDY: This study aimed to investigate the oral absorption of PAs and PA N-oxides for better understanding of their significant differences in toxicokinetics and toxic potency. MATERIALS AND METHODS: The oral absorption of PAs and PA N-oxides in rats and in rat in situ single pass intestine perfusion model was investigated. The intestinal permeability and absorption mechanisms of five pairs of PAs and PA N-oxides were evaluated by using Caco-2 monolayer model. RESULTS: The plasma concentrations of total PAs and PA N-oxides within 0-60 min were significantly lower in rats orally treated with a PA N-oxide-containing herbal alkaloid extract than with a PA-containing herbal alkaloid extract at the same dose, indicating that the absorption of PA N-oxides was lower than that of PAs. Using the rat in situ single pass intestine perfusion model, less cumulative amounts of retrorsine N-oxide in mesenteric blood were observed compared to that of retrorsine. In Caco-2 monolayer model, all five PAs showed absorption with Papp AtoB values [(1.43-16.26) × 10-6 cm/s] higher than those of corresponding N-oxides with Papp AtoB values lower than 1.35 × 10-6 cm/s. A further mechanistic study demonstrated that except for senecionine N-oxide, retrorsine N-oxide, and lycopsamine N-oxide, all PAs and PA N-oxides investigated were absorbed via passive diffusion. While, for these 3 PA N-oxides, in addition to passive diffusion as their primary transportation, efflux transporter-mediated active transportation was also involved but to a less extent with the efflux ratio of 2.31-3.41. Furthermore, a good correlation between lipophilicity and permeability of retronecine-type PAs and their N-oxides with absorption via passive diffusion was observed, demonstrating that PAs have a better oral absorbability than that of the corresponding PA N-oxides. CONCLUSION: We discovered that among many contributors, the lower intestinal absorption of PA N-oxides was the initiating contributor that caused differences in toxicokinetics and toxic potency between PAs and PA N-oxides.

Metallic elements study on fine and coarse particulates during daytime and nighttime periods at a traffic sampling site.

Fine (PM2.5) and coarse (PM(2.5-10)) particulates were collected simultaneously by using a versatile air pollutant system at a traffic sampling site during daytime and nighttime sampling periods during August 2003 to March 2004. A flame atomic absorption spectrophotometer coupled with hollow cathode lamps were used for chemical analysis. Enrichment factor and principal component analysis were used to compare chemical components and to find the possible emission sources at this traffic sampling site. The variation of metallic element concentrations on fine and coarse particulates during daytime and nighttime was also discussed in this study. Soil dust, traffic exhaust, marine salt and anthropogenic activities were the major pollutant sources at the traffic sampling site in central Taiwan.

Fine (PM2.5), coarse (PM2.5-10), and metallic elements of suspended particulates for incense burning at Tzu Yun Yen temple in central Taiwan.

Ambient suspended particulate concentrations were measured at Tzu Yun Yen temple (120 degrees, 34('), 10(") E; 24 degrees, 16('), 12(") N) in this study. This is representative of incense burning and semi-open sampling sites. The Universal-sampler collected fine and coarse particle material was used to measure suspended particulate concentrations, and sampling periods were from 16/08/2001 to 2/1/2002 at Tzu Yun Yen temple. In addition, metallic element concentrations, compositions of PM(2.5) and PM(2.5-10) for incense burning at Tzu Yun Yen temple were also analyzed in this study. The PM(2.5)/PM(10) ratios ranged between 31% and 87% and averaged 70+/-11% during incense the burning period, respectively. The median metallic element concentration order for these elements is Fe>Zn>Cr>Cd>Pb>Mn>Ni>Cu in fine particles (PM(2.5)) at the Tzu Yun Yen temple sampling site. The median metallic element concentration order for these elements is Fe>Zn>Cr>Pb>Cd>Ni>Mn>Cu in coarse particle (PM(2.5-10)) at the Tzu Yun Yen temple sampling site. Fine particulates (PM(2.5)) are the main portion of PM(10) at Tzu Yun Yen temple in this study. From the point of view of PM(10), these data reflect that the elements Fe, Zn, and Cr were the major elements distributed at Tzu Yun Yen temple in this study.