title: The Association between Elevated Levels of Peripheral Serotonin and Its Metabolite - 5-Hydroxyindoleacetic Acid and Bone Strength and Metabolism in Growing Rats with Mild Experimental Chronic Kidney Disease.
abstract: Chronic kidney disease (CKD) is associated with disturbances in bone strength and metabolism. The alterations of the serotonergic system are also observed in CKD. We used the 5/6 nephrectomy model of CKD to assess the impact of peripheral serotonin and its metabolite- 5-hydroxyindoleacetic acid on bone biomechanical properties and metabolism in growing rats. The animals were sacrificed one and three months after nephrectomy. Biomechanical properties were determined on two different bone types: the cortical bone of the femoral diaphysis using three-point bending test and the mixed cortico-trabecular bone by the bending test of the femoral neck. Biomechanical tests revealed preserved cortical bone strength, whereas work to fracture (W) and yield load (Fy) of mixed cortico-trabecular bone were significantly lower in CKD compared to controls. Serum activity of alkaline phosphatase (ALP), a bone formation marker, and tartrate-resistant acid phosphatase (TRACP 5b) reflecting bone resorption, were similar in CKD and controls. ALP was associated with lower femoral stiffness and strength, and higher displacements and W. TRACP 5b was inversely associated with cortical Fu and W. The elevated peripheral serotonergic system in CKD was: inversely associated with stiffness but positively related to the displacements and W; inversely associated with cortical Fy but positively correlated with this parameter in cortico-trabecular bone; inversely associated with ALP in controls but positively correlated with this biomarker in CKD animals. In conclusion, this study demonstrates the distinct effect of mild degree of CKD on bone strength in rapidly growing rats. The impaired renal function affects the peripheral serotonin metabolism, which in turn may influence the strength and metabolism of bones in these rats. This relationship seems to be beneficial on the biomechanical properties of the cortico-trabecular bone, whereas the cortical bone strength can be potentially reduced.
authors.affiliation: Department of Pharmacodynamics, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Pawlak
authors.affiliation: Department of Monitored Pharmacotherapy, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Oksztulska-Kolanek
authors.affiliation: Department of Monitored Pharmacotherapy, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Znorko
authors.affiliation: Department of Monitored Pharmacotherapy, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Domaniewski
authors.affiliation: Department of Toxicology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Rogalska
authors.affiliation: Department of Toxicology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Alicja
authors.initials: A
authors.lastname: Roszczenko
authors.affiliation: Department of Toxicology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Małgorzata Michalina
authors.initials: MM
authors.lastname: Brzóska
authors.affiliation: Department of General Pathomorphology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Pryczynicz
authors.affiliation: Department of General Pathomorphology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Kemona
authors.affiliation: Department of Monitored Pharmacotherapy, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Krystyna
authors.initials: K
authors.lastname: Pawlak
mesh_terms: D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001696:Biomechanical Phenomena; D001835:Body Weight; D000071556:Cancellous Bone / Q000378:metabolism / Q000503:physiopathology*; D000071538:Cortical Bone / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D005269:Femur / Q000378:metabolism / Q000503:physiopathology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D012701:Serotonin / Q000378:metabolism*
chemical_list: D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D000469:Alkaline Phosphatase