Premium
A clinically relevant combination treatment of doxorubicin and cyclophosphamide does not induce hepatotoxicity in C57BL/6J mice
Author(s) -
Salamat Julia,
Abbott Kodye,
Flannery Patrick,
Majrashi Mohammed,
Almaghrabi Mohammed,
Govindarajulu Manoj,
Ramesh Sindhu,
Sandey Maninder,
Onteru Suneel,
Huang ChenChe,
Iwaki Yoshimi,
Gill Kristina,
Narayanan Natasha,
McElroy Edwin,
Desai Darshini,
Nadar Rishi,
Ward Kaylie,
Ledbetter Elizabeth,
Moore Timothy,
Dhanasekaran Muralikrishnan,
Pondugula Satyanarayana
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.02914
Subject(s) - medicine , doxorubicin , pharmacology , alanine transaminase , cyclophosphamide , creatinine , concomitant , albumin , alkaline phosphatase , bilirubin , chemotherapy , liver injury , chemistry , enzyme , biochemistry
Chronic exposure to chemotherapeutics can lead to severe adverse events including hepatotoxicity. A combination chemotherapy regimen of doxorubicin (DOX) and cyclophosphamide (CPS) is employed in treatment of several cancers such as leukemia, lymphoma, and breast cancer. It is currently not well understood whether a combination therapy of DOX and CPS can induce hepatotoxicity. We therefore sought to determine whether co‐administration of DOX and CPS at their clinically relevant doses and frequency results in hepatotoxicity. Male C57BL/6J mice received one intraperitoneal injection of saline or DOX‐2mg /kg and CPS‐50mg/kg once a week for 4 weeks. After the treatment period, liver histology and various serum biomarkers of hepatotoxicity were assessed. Co‐treatment of DOX and CPS did not alter the serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin, albumin, globulin, or total protein. Similarly, co‐administration of DOX and CPS did not result in a noticeable change in liver histology. However, it was notable that the concomitant treatment with DOX and CPS resulted in a significant increase in serum levels of aspartate aminotransferase (AST). Elevated serum AST levels were also associated with increased serum creatinine kinase (CK) levels, suggesting that the elevated serum AST levels are likely due to muscle injury following the co‐administration of DOX and CPS. Taken together, our results, for the first time, suggest that co‐administration of DOX and CPS, at their clinically relevant doses and frequency, does not induce a significant hepatotoxicity in the mice.