Sub-toxic events induced by truck speed-facilitated PM2.5 and its counteraction by epigallocatechin-3-gallate in A549 human lung cells.

To distinguish the influences of fuel type and truck speed on chemical composition and sub-toxic effects of particulates (PM2.5) from engine emissions, biomarkers-interleukin-6 (IL-6), cytochrome P450 (CYP) 1A1, heme oxygenase (HO)-1, and NADPH-quinone oxidoreductase (NQO)-1-were studied in A549 human lung cells. Fuel type and truck speed preferentially affected the quantity and ion/polycyclic aromatic hydrocarbon (PAH) composition of PM2.5, respectively. Under idling operation, phenanthrene was the most abundant PAH. At high speed, more than 50% of the PAHs had high molecular weight (HMW), of which benzo[a]pyrene (B[a]P), benzo[ghi]perylene (B[ghi]P), and indeno[1,2,3-cd]pyrene (I[cd]P) were the main PAHs. B[a]P, B[ghi]P, and I[cd]P caused potent induction of IL-6, CYP1A1, and NQO-1, whereas phenanthrene mildly induced CYP1A1. Based on the PAH-mediated induction, the predicted increases in biomarkers were positively correlated with the measured increases. HMW-PAHs contribute to the biomarker induction by PM2.5, at high speed, which was reduced by co-exposure to epigallocatechin-3-gallate.

Effects of Shengmai San on key enzymes involved in hepatic and intestinal drug metabolism in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Shengmai San (SMS) has been commonly used as a traditional Chinese medicine for the treatment of cardiovascular disorders, of which drug interactions need to be assessed for the safety concern. There is little evidence for the alterations of hepatic and intestinal drug-metabolizing enzymes after repeated SMS treatments to assess drug interactions. AIM OF THE STUDY: The studies aim to illustrate the effects of repeated treatments with SMS on cytochrome P450s (CYPs), reduced nicotinamide adenine dinucleotide (phosphate)-quinone oxidoreductase (NQO), uridine diphosphate-glucuronosyltransferase (UGT), and glutathione S-transferase (GST) using in vivo rat model. MATERIALS AND METHODS: The SMS was prepared using Schisandrae Fructus, Ginseng Radix, and Ophiopogonis Radix (OR) (1:2:2). Chromatographic analyses of decoctions were performed using ultra-performance liquid chromatography (UPLC) and LC-mass spectrometry. Sprague-Dawley rats were orally treated with the SMS and its component herbal decoctions for 2 or 3 weeks. Hepatic and intestinal enzyme activities were determined. CYP3A expression and the kinetics of intestinal nifedipine oxidation (NFO, a CYP3A marker reaction) were determined. RESULTS: Schisandrol A, schisandrin B, ginsenoside Rb1 and ophiopogonin D were identified in SMS. SMS selectively suppressed intestinal, but not hepatic, NFO activity in a dose- and time-dependent manner. Hepatic and intestinal UGT, NQO and GST activities were not affected. A 3-week SMS treatment decreased the maximal velocity of intestinal NFO by 50%, while the CYP3A protein level remained unchanged. Among SMS component herbs, the decoction of OR decreased intestinal NFO activity. CONCLUSIONS: These findings demonstrate that 3-week treatment with SMS and OR suppress intestinal, but not hepatic CYP3A function. It suggested that the potential interactions of SMS with CYP 3A drug substrates should be noticed, especially the drugs whose bioavailability depends heavily on intestinal CYP3A.