Supplementary Material for: Stereoselective Inhibition of Renal Basolateral Human Organic Anion Transporter 3 by Lansoprazole Enantiomers

Lansoprazole, a proton pump inhibitor, potently inhibits human organic anion transporter, hOAT3 (SLC22A8). Lansoprazole has an asymmetric atom in its structure and is clinically administered as a racemic mixture of (R)-and (S)-enantiomers. However, little is known about the stereoselective inhibitory potencies of lansoprazole against hOAT3 and its homolog, hOAT1. In the present study, the stereoselective inhibitory effect of lansoprazole was evaluated using hOAT1-and hOAT3-expressing cultured cells. hOAT1 and hOAT3 transported [¹⁴C]<i>p</i>-aminohippurate and [³H]estrone-3-sulfate (ES) with Michaelis-Menten constants of 29.8 ± 4.0 and 30.1 ± 9.0 µmol/L respectively. Lansoprazole enantiomers inhibited hOAT1- and hOAT3-mediated transport of each substrate in a concentration-dependent manner. The IC₅₀ value of (S)-lansoprazole against hOAT3-mediated transport of [³H]ES (0.61 ± 0.08 µmol/L) was significantly lower than that of (R)-lansoprazole (1.75 ± 0.31 µmol/L). In contrast, stereoselectivity was not demonstrated for the inhibition of hOAT1. Furthermore, (S)-lansoprazole inhibited hOAT3-mediated transport of pemetrexed and methotrexate (hOAT3 substrates) more strongly than the corresponding (R)-lansoprazole. This study is the first to demonstrate that the stereoselective inhibitory potency of (S)-lansoprazole against hOAT3 is greater than that of (R)-lansoprazole. The present findings provide novel information about the drug interactions associated with lansoprazole

Supplementary Material for: Dietary Fiber Consumption Decreases the Risks of Overweight and Hypercholesterolemia in Japanese Children

<b><i>Aims:</i></b> It remains inconclusive whether high dietary fiber intake decreases the risk of obesity, hypercholesterolemia or high blood pressure during childhood. Therefore, this study investigated the relationships of dietary fiber intake with weight status and related clinical parameters among Japanese children. <b><i>Methods:</i></b> We analyzed the data of 5,600 subjects aged 10-11 years, between 2006 and 2010. Fiber intake was assessed using the Brief-type Diet History Questionnaire. Body height and weight and blood pressure were measured. Serum levels of total cholesterol, low- and high-density lipoprotein cholesterol and triglycerides were analyzed. Fiber intake was categorized into quintiles, and multivariate models were used to adjust for lifestyle factors. <b><i>Results:</i></b> Total fiber intake decreased the risks of overweight and high total cholesterol (OR Quintile 5 vs. Quintile 1 overweight: 0.71 for boys, 0.40 for girls; total cholesterol: 0.60 for boys, 0.66 for girls). Water-soluble fiber intake was associated with a lower risk of high blood pressure, although the ORs were not significant. <b><i>Conclusions:</i></b> Increasing the dietary fiber intake in Japanese children may have favorable effects on overweight and hypercholesterolemia