title: In vivo kinetics of the uremic toxin p-cresyl sulfate in mice with variable renal function.
abstract: Uremic toxins such as p-cresyl sulfate (PCS) are associated with increased mortality for chronic kidney disease (CKD) patients, but in vivo PCS toxicity studies are limited due to the lack of a standard animal model. To establish such a model, we measured the pharmacokinetics of PCS in mice with variable renal function. Male Balb/c mice subjected to 5/6 nephrectomy (CRF), unilateral nephrectomy (UNX), or no surgery (controls) were given PCS (po, 50 mg/kg). Blood samples were collected over time and plasma PCS concentrations were measured. Over 4 h, PCS was significantly higher in the plasma of CRF mice (63.28 ± 2.76 mg/L), compared to UNX mice (3.11 ± 0.64 mg/L) and controls (0.39 ± 0.12 mg/L). The PCS half-life was greatest in CRF mice (12.07 ± 0.12 h), compared to 0.79 ± 0.04 h in UNX mice and 0.48 ± 0.02 h in control mice. However, the potential presence of additional uremic toxins along with PCS in CRF mice and rapid PCS clearance in control mice suggest that the UNX mouse would be a better PCS model to study toxicity.
authors.affiliation: Department of Cardiology, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Ni
authors.forename: Wenli
authors.initials: W
authors.lastname: Zhang
authors.forename: Zhengbin
authors.initials: Z
authors.lastname: Zhu
authors.forename: Jinzhou
authors.initials: J
authors.lastname: Zhu
authors.forename: Run
authors.initials: R
authors.lastname: Du
authors.forename: Yajun
authors.initials: Y
authors.lastname: Jing
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
authors.forename: Ruiyan
authors.initials: R
authors.lastname: Zhang
mesh_terms: D000818:Animals; D003408:Cresols / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D006207:Half-Life; D007677:Kidney Function Tests; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009392:Nephrectomy; D051436:Renal Insufficiency, Chronic / Q000503:physiopathology*; D013463:Sulfuric Acid Esters / Q000493:pharmacokinetics*; D013997:Time Factors
chemical_list: D003408:Cresols; D013463:Sulfuric Acid Esters; C408690:4-cresol sulfate
keywords: Kinetics; P-cresyl sulfate; Uremic toxins; mouse model