A link between central kynurenine metabolism and bone strength in rats with chronic kidney disease

PeerJ

article

Bartlomiej Kalaska¹  Krystyna Pawlak²  Ewa Oksztulska-Kolanek²  Tomasz Domaniewski²  Beata Znorko²  Malgorzata Karbowska¹  Aleksandra Citkowska¹  Joanna Rogalska³  Alicja Roszczenko³  Malgorzata M. Brzoska³  Dariusz Pawlak¹ 

[1] Department of Pharmacodynamics, Medical University of Bialystok;Department of Monitored Pharmacotherapy, Medical University of Bialystok;Department of Toxicology, Medical University of Bialystok

关键词: Bone disorders;    Chronic kidney disease;    Kynurenine pathway;    Brain;   

DOI  :  10.7717/peerj.3199

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

BackgroundDisturbances in mineral and bone metabolism represent one of the most complex complications of chronic kidney disease (CKD). Serotonin, a monoamine synthesized from tryptophan, may play a potential role in bone metabolism. Brain-derived serotonin exerts a positive effect on the bone structure by limiting bone resorption and enhancing bone formation. Tryptophan is the precursor not only to the serotonin but also and primarily to kynurenine metabolites. The ultimate aim of the present study was to determine the association between central kynurenine metabolism and biomechanical as well as geometrical properties of bone in the experimental model of the early stage of CKD.MethodsThirty-three Wistar rats were randomly divided into two groups (sham-operated and subtotal nephrectomized animals). Three months after surgery, serum samples were obtained for the determination of biochemical parameters, bone turnover biomarkers, and kynurenine pathway metabolites; tibias were collected for bone biomechanical, bone geometrical, and bone mass density analysis; brains were removed and divided into five regions for the determination of kynurenine pathway metabolites.ResultsSubtotal nephrectomized rats presented higher serum concentrations of creatinine, urea nitrogen, and parathyroid hormone, and developed hypocalcemia. Several biomechanical and geometrical parameters were significantly elevated in rats with experimentally induced CKD. Subtotal nephrectomized rats presented significantly higher kynurenine concentrations and kynurenine/tryptophan ratio and significantly lower tryptophan levels in all studied parts of the brain. Kynurenine in the frontal cortex and tryptophan in the hypothalamus and striatum correlated positively with the main parameters of bone biomechanics and bone geometry.DiscussionIn addition to the complex mineral, hormone, and metabolite changes, intensified central kynurenine turnover may play an important role in the development of bone changes in the course of CKD.

【 授权许可】

CC BY