title: Indoxyl Sulfate as a Mediator Involved in Dysregulation of Pulmonary Aquaporin-5 in Acute Lung Injury Caused by Acute Kidney Injury.
abstract: High mortality of acute kidney injury (AKI) is associated with acute lung injury (ALI), which is a typical complication of AKI. Although it is suggested that dysregulation of lung salt and water channels following AKI plays a pivotal role in ALI, the mechanism of its dysregulation has not been elucidated. Here, we examined the involvement of a typical oxidative stress-inducing uremic toxin, indoxyl sulfate (IS), in the dysregulation of the pulmonary predominant water channel, aquaporin 5 (AQP-5), in bilateral nephrectomy (BNx)-induced AKI model rats. BNx evoked AKI with the increases in serum creatinine (SCr), blood urea nitrogen (BUN) and serum IS levels and exhibited thickening of interstitial tissue in the lung. Administration of AST-120, clinically-used oral spherical adsorptive carbon beads, resulted in a significant decrease in serum IS level and thickening of interstitial tissue, which was accompanied with the decreases in IS accumulation in various tissues, especially lung. Interestingly, a significant decrease in AQP-5 expression of lung was observed in BNx rats. Moreover, the BNx-induced decrease in pulmonary AQP-5 protein expression was markedly restored by oral administration of AST-120. These results suggest that BNx-induced AKI causes dysregulation of pulmonary AQP-5 expression, in which IS could play a toxico-physiological role as a mediator involved in renopulmonary crosstalk.
authors.affiliation: Department of Clinical Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan. 159y1003@st.kumamoto-u.ac.jp.
authors.forename: Nozomi
authors.initials: N
authors.lastname: Yabuuchi
authors.affiliation: Department of Clinical Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan. berry.of.kumamoto.antonio@gmail.com.
authors.forename: Masataka
authors.initials: M
authors.lastname: Sagata
authors.affiliation: Department of Clinical Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan. saigo@fc.kuh.kumamoto-u.ac.jp.|Department of Pharmacy, Kumamoto University Hospital, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan. saigo@fc.kuh.kumamoto-u.ac.jp.
authors.forename: Chika
authors.initials: C
authors.lastname: Saigo
authors.affiliation: Department of Clinical Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan. 157y3108@st.kumamoto-u.ac.jp.
authors.forename: Go
authors.initials: G
authors.lastname: Yoneda
authors.affiliation: Department of Clinical Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan. a-y.o.atemak_happiness7@docomo.ne.jp.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Clinical Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan. 18nomura@gmail.com.
authors.forename: Yui
authors.initials: Y
authors.lastname: Nomura
authors.affiliation: Department of Hemodialysis and Apheresis, Kumamoto University Hospital, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan. kazuhiko-nishi@fc.kuh.kumamoto-u.ac.jp.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nishi
authors.affiliation: Department of Pharmacy, Kumamoto University Hospital, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan. fujinorica@gmail.com.
authors.forename: Rika
authors.initials: R
authors.lastname: Fujino
authors.affiliation: Department of Clinical Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan. hjono@fc.kuh.kumamoto-u.ac.jp.|Department of Pharmacy, Kumamoto University Hospital, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan. hjono@fc.kuh.kumamoto-u.ac.jp.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Jono
authors.affiliation: Department of Clinical Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan. saitohide@fc.kuh.kumamoto-u.ac.jp.|Department of Pharmacy, Kumamoto University Hospital, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan. saitohide@fc.kuh.kumamoto-u.ac.jp.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Saito
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood* / Q000150:complications; D055371:Acute Lung Injury / Q000209:etiology / Q000378:metabolism*; D000818:Animals; D051402:Aquaporin 5 / Q000235:genetics / Q000378:metabolism*; D007200:Indican / Q000097:blood*; D008168:Lung / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C496040:Aqp5 protein, rat; D051402:Aquaporin 5; D007200:Indican
keywords: acute kidney injury; acute lung injury; aquaporin-5; indoxyl sulfate