Mechanistic studies of PEG-asparaginase-induced liver injury and hepatic steatosis in mice.
10.1016/j.apsb.2021.11.022
- Author:
Gundala Venkata Naveen KUMAR
1
;
Keito HOSHITSUKI
1
;
Sanjay RATHOD
1
;
Manda J RAMSEY
1
;
Lauren KOKAI
2
;
Erin E KERSHAW
3
;
Wen XIE
1
;
Christian A FERNANDEZ
1
Author Information
1. Department of Pharmaceutical Sciences and Center for Pharmacogenetics, University of Pittsburgh School of Pharmacy, Pittsburgh, PA 15261, USA.
2. Department of Plastic Surgery, University of Pittsburgh and the McGowan Institute for Regenerative Medicine, Pittsburgh, PA 15261, USA.
3. University of Pittsburgh, Division of Endocrinology, Department of Medicine, Pittsburgh, PA 15261, USA.
- Publication Type:Journal Article
- Keywords:
Adipose tissue;
Adverse drug reaction;
Amino acid response;
Asparaginase;
Hepatic steatosis;
Leukemia;
Lipolysis;
Liver injury
- From:
Acta Pharmaceutica Sinica B
2021;11(12):3779-3790
- CountryChina
- Language:English
-
Abstract:
PEGylated-l-asparaginase (PEG-ASNase) is a chemotherapeutic agent used to treat pediatric acute lymphoblastic leukemia (ALL). Its use is avoided in adults due to its high risk of liver injury including hepatic steatosis, with obesity and older age considered risk factors of the injury. Our study aims to elucidate the mechanism of PEG-ASNase-induced liver injury. Mice received 1500 U/kg of PEG-ASNase and were sacrificed 1, 3, 5, and 7 days after drug administration. Liver triglycerides were quantified, and plasma bilirubin, ALT, AST, and non-esterified fatty acids (NEFA) were measured. The mRNA and protein levels of genes involved in hepatic fatty acid synthesis,
