Application of a mechanistic model to evaluate putative mechanisms of tolvaptan drug-induced liver injury and identify patient susceptibility factors

JL Woodhead, WJ Brock, SE Roth… - Toxicological …, 2017 - academic.oup.com
Tolvaptan is a selective vasopressin V2 receptor antagonist, approved in several countries
for the treatment of hyponatremia and autosomal dominant polycystic kidney disease (ADPKD…

Editor's highlight: Candidate risk factors and mechanisms for tolvaptan-induced liver injury are identified using a collaborative cross approach

M Mosedale, Y Kim, WJ Brock, SE Roth… - Toxicological …, 2017 - academic.oup.com
Clinical trials of tolvaptan showed it to be a promising candidate for the treatment of
Autosomal Dominant Polycystic Kidney Disease (ADPKD) but also revealed potential for …

miR-122 release in exosomes precedes overt tolvaptan-induced necrosis in a primary human hepatocyte micropatterned coculture model

…, BR Ware, SR Khetani, J Lu, WJ Brock… - Toxicological …, 2018 - academic.oup.com
Idiosyncratic drug-induced liver injury (IDILI) is thought to often result from an adaptive immune
attack on the liver. However, it has been proposed that the cascade of events culminating …

Inhibition of human hepatic bile acid transporters by tolvaptan and metabolites: contributing factors to drug-induced liver injury?

…, KM Freeman, M Pan, WJ Brock… - Toxicological …, 2016 - academic.oup.com
Tolvaptan is a vasopressin V 2 -receptor antagonist that has shown promise in treating
Autosomal Dominant Polycystic Kidney Disease (ADPKD). Tolvaptan was, however, associated …

Quantitative systems toxicology modeling predicts that reduced biliary efflux contributes to tolvaptan hepatotoxicity

JJ Beaudoin, WJ Brock, PB Watkins… - Clinical …, 2021 - Wiley Online Library
Patients with autosomal dominant polycystic kidney disease (ADPKD) exhibit enhanced
susceptibility to tolvaptan hepatotoxicity relative to other patient populations. In a rodent model …

Oral repeat dose and reproductive toxicity of the chlorinated flame retardant Dechlorane Plus

WJ Brock, RE Schroeder, CA McKnight… - … journal of toxicology, 2010 - journals.sagepub.com
This study consisted of a 28-day oral repeat dose (repeat dose toxicity [RDT]) phase and a
developmental and reproductive (developmental and reproductive toxicity [DART]) phase with …

Efruxifermin, a long‐acting Fc‐fusion FGF21 analogue, reduces body weight gain but does not increase sympathetic tone or urine volume in Sprague Dawley rats

EJ Tillman, WJ Brock, T Rolph - British Journal of …, 2022 - Wiley Online Library
Background and Purpose Analogues of fibroblast growth factor 21 (FGF21) demonstrate
diverse metabolic benefits in preclinical models of type 2 diabetes, dyslipidaemia and non‐…

Bile acids as potential biomarkers to assess liver impairment in polycystic kidney disease

WJ Brock, JJ Beaudoin, JR Slizgi… - … journal of toxicology, 2018 - journals.sagepub.com
Polycystic kidney disease is characterized by the progressive development of kidney cysts
and declining renal function with frequent development of cysts in other organs including the …

Food safety: risk assessment methodology and decision-making criteria

WJ Brock, JV Rodricks, A Rulis… - … journal of toxicology, 2003 - journals.sagepub.com
As our scientific technology grows, risk assessment methods become more complex and,
therefore, open to greater scientific debate. Risk assessment has always been a part of the …

Altered expression and function of hepatic transporters in a rodent model of polycystic kidney disease

…, JJ Beaudoin, K Ito, D Fu, SE Roth, WJ Brock… - Drug Metabolism and …, 2019 - ASPET
Autosomal dominant polycystic kidney disease (ADPKD) is a common form of inherited
polycystic kidney disease (PKD) and is a leading cause of kidney failure. Fluid-filled cysts …