@article{oai:kumadai.repo.nii.ac.jp:00028490,
 author = {齋藤, 秀之 and 吉村, 美里 and 西郷, 智香 and 小森, めぐみ and 野村, 祐衣 and 山本, 悠子 and Yamamoto, Yuko and 佐潟, 雅隆 and 脇田, 紋佳 and 中馬, 江里奈 and 西, 一彦 and 城野, 博史 and Saito, Hideyuki and Yoshimura, Misato and Saigo, Chika and Komori, Megumi and Nomura, Yui and 山本, 裕子 and Yamamoto, Yuko and Sagata, Masataka and Wakida, Ayaka and Chuman, Erina and Nishi, Kazuhiko and Jono, Hirofumi},
 issue = {1},
 journal = {Toxicological Sciences},
 month = {Sep},
 note = {application/pdf, 論文(Article), Ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) is evoked by diverse pathophysiological conditions and/or surgical procedures. Here, we evaluated the nephropreventive effect of sulfotransferase (SULT) inhibitors, quercetin and resveratrol, which hamper hepatic indoxyl sulfate (IS) production. I/R of the kidney caused severe renal injury with  marked accumulation of serum and renal IS and urinary excretion of kidney injury molecule-1. Oral administration of AST-120 resulted in a significant restoration of kidney injury, suggesting that uremic toxins, which can be suppressed or adsorbed by AST-120 in the intestine, contribute to the progression or development of I/R-induced AKI. Oral administration of resveratrol or quercetin, SULT inhibitors, suppressed IS accumulation, accompanied by significant amelioration of renal dysfunction. The expression of nuclear factor E2-related factor 2 (Nrf2) in the renal nuclear fractions was markedly elevated by renal I/R, but suppressed by treatment with SULT inhibitors. IS is primarily taken up by HK-2 cells derived from human proximal tubular cells via organic anion transporters, which then evokes activation of Nrf2, most likely due to intracellular oxidative stress. Renal basolateral organic anion transporters OAT1 and OAT3, which mediate renal tubular uptake of IS in basolateral membrane, were markedly down-regulated by renal I/R, but  restored by SULT inhibitors. Our results suggest that renal accumulation of IS in ischemic AKI induces oxidative stress and downregulation of organic anion transporters resulting in kidney damage, which could be restored to some extent by inhibiting hepatic SULT activity as a nephropreventive target., http://toxsci.oxfordjournals.org/content/early/2014/06/25/toxsci.kfu119.abstract},
 pages = {206--217},
 title = {Hepatic Sulfotransferase as a Nephropreventing Target by Suppression of the Uremic Toxin Indoxyl Sulfate Accumulation in Ischemic Acute Kidney Injury},
 volume = {141},
 year = {2014},
 yomi = {ヤマモト, ユウコ and ヤマモト, ユウコ}
}