S-1 is a new oral antitumor drug and consists of tegafur (FT) and the following two types of biological modulators: 5-chloro-2,4-dihydroxypyrimidine (CDHP) and potassium oxonate
(Oxo) with molar ratio of 1: 0.4:1, and it was first used in clinical practice in 1999 .
The other is potassium oxonate
, which localizes in the mucosa of the gastrointestinal tract after oral administration and alleviates gastrointestinal toxicities induced by 5-FU [5, 6].
The kidney homogenates were added to mixture containing [[sup.15][N.sub.2]] xanthine (0.4mmol/L), [NAD.sup.+] (0.4mmol/L), and oxonate
(0.013 mmol/L) in 20 mmol/L Tris buffer (pH 8.5) and were incubated at 37[degrees] C for 30 min.
Sodium urate, potassium oxonate
, adenine, allopurinol, colchicine, XOD, and xanthine were purchased from Sigma-Aldrich, USA.
Quercetin isolated from Biota orientalis reduces UA in hyperuricemia mice caused by oxonate
, which is partly due to its inhibition on XO activity in the liver .
Hyperuricemia was induced by potassium oxonate
. Sixty adult male rats weighing 1155 gm were randomly distributed into six groups (10 animals in each group).
Furthermore, luteolin which is a potent inhibitor of XO in vitro does not produce any observable hypouricemic effects after acute oral treatment in potassium oxonate
treated rats (Sarawek et al., 2008).
S-1 is a combination of tegafur, a prodrug of 5-FU, with two enzyme inhibitors, 5 chloro-2,4-dihydropyrimidine (CDHP) and potassium oxonate
. CDHP increases the activity of 5FU by inhibiting dihydropyrimidine dehydrogenase, the rate-limiting enzyme for the catabolism of 5-FU, while potassium oxonate
decreases the gastrointestinal toxicity of 5-FU by preventing phosphorylation in the gastrointestinal tract.
Xanthine, indomethacin, uric acid, linoleic acid and potassium persulfate ([greater than or equal to] 99%), allopurinol, caffeic acid, chlorogenic acid, ABTS (azinobis 2,2-(3-ethylbenzothiazoline-6-sulphonic acid)), DPPH (2,2-diphenyl-1-picrylhydrazyl), quercetin and gallic acid (98%), potassium oxonate
and trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2carboxylic acid) (97%), rutin ([greater than or equal to] 95%), [beta]-carotene ([greater than or equal to] 93%), Tween 40, and Folin-Ciocalteu reagent were obtained from Sigma-Aldrich (USA).
We then examined if these two compounds were effective in reducing serum uric acid levels in a hyperuricemic mouse model induced by potassium oxonate
. We found that the two steroidal glycosides possess potent uricosuric effect in hyperuricemic mice through decreasing renal mURAT1 mainly and inhibiting XOD activity in a certain extent, which contribute to the enhancement of uric acid excretion and attenuate hyperuricemia-induced renal dysfunction.
(dissolved in PBS; 250 mg/kg) was administered to all mice except those in the Nor group intraperitoneally, 1 h before the last pretreatment on the 7th day (mice in the Nor group received PBS instead of potassium oxonate
(2006) demonstrated that cassia oil significantly reduced serum and hepatic urate levels in the hyperuricemia mice caused by oxonate