title: Indoxyl sulfate exacerbates low bone turnover induced by parathyroidectomy in young adult rats.
abstract: Low-turnover bone disease is one of the bone abnormalities observed in patients with chronic kidney disease (CKD) and is recognized to be associated with low serum parathyroid hormone (PTH) level and skeletal resistance to PTH. Indoxyl sulfate (IS) is a representative uremic toxin that accumulates in the blood as renal dysfunction progresses in CKD patients. A recent in vitro study using an osteoblastic cell culture system suggests that IS has an important role in the pathogenesis of low bone turnover through induction of skeletal resistance to PTH. However, the effects of IS on the progression of low bone turnover have not been elucidated. In the present study, we produced rats with low bone turnover by performing parathyroidectomy (PTX) and fed these rats a diet containing indole, a precursor of IS, to elevate blood IS level from indole metabolism. Bone metabolism was evaluated by measuring histomorphometric parameters of secondary spongiosa of the femur. Histomorphometric analyses revealed significant decreases in both bone formation-related parameters and bone resorption-related parameters in PTX rats. In indole-treated PTX rats, further decreases in bone formation-related parameters were observed. In addition, serum alkaline phosphatase activity, a bone formation marker, and bone mineral density of the tibia tended to decrease in indole-treated PTX rats. These findings strongly suggest that IS exacerbates low bone turnover through inhibition of bone formation by mechanisms unrelated to skeletal resistance to PTH.
authors.affiliation: Safety Research Center, Kureha Corporation, Tokyo 169-8503, Japan; Cooperative Major in Advanced Health Science, Tokyo University of Agriculture and Technology, Tokyo 184-8588, Japan. Electronic address: junya-hirata@kureha.co.jp.
authors.forename: Junya
authors.initials: J
authors.lastname: Hirata
authors.affiliation: Safety Research Center, Kureha Corporation, Tokyo 169-8503, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Hirai
authors.affiliation: Safety Research Center, Kureha Corporation, Tokyo 169-8503, Japan.
authors.forename: Hirobumi
authors.initials: H
authors.lastname: Asai
authors.affiliation: Cooperative Major in Advanced Health Science, Tokyo University of Agriculture and Technology, Tokyo 184-8588, Japan.
authors.forename: Chiho
authors.initials: C
authors.lastname: Matsumoto
authors.affiliation: Cooperative Major in Advanced Health Science, Tokyo University of Agriculture and Technology, Tokyo 184-8588, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Inada
authors.affiliation: Cooperative Major in Advanced Health Science, Tokyo University of Agriculture and Technology, Tokyo 184-8588, Japan.
authors.forename: Chisato
authors.initials: C
authors.lastname: Miyaura
authors.affiliation: Safety Research Center, Kureha Corporation, Tokyo 169-8503, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yamato
authors.affiliation: Safety Research Center, Kureha Corporation, Tokyo 169-8503, Japan.
authors.forename: Mie
authors.initials: M
authors.lastname: Watanabe-Akanuma
mesh_terms: D000818:Animals; D015519:Bone Density; D016723:Bone Remodeling / Q000502:physiology*; D004195:Disease Models, Animal; D007200:Indican / Q000378:metabolism*; D008297:Male; D010281:Parathyroid Hormone / Q000378:metabolism; D016105:Parathyroidectomy / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051436:Renal Insufficiency, Chronic / Q000150:complications* / Q000503:physiopathology
chemical_list: D010281:Parathyroid Hormone; D007200:Indican
keywords: Chronic kidney disease; Indole; Indoxyl sulfate; Low bone turnover; Parathyroidectomy