Proceedings of The Physiological Society
University College London (2003) J Physiol 547P, PC1
Sex comparisons in doxorubicin-induced muscle and liver damage
T. Phillips, Y.M. Jang and C. Leeuwenburgh
University of Florida, Biochemistry of Aging Laboratory, College of Health and Human Performance, PO Box 118206, Gainesville, FL 32611, USA
Doxorubicin is a member of the anthracycline family of chemotherapeutic agents used to treat many forms of cancer, although its clinical application has been limited due to the cardiotoxicity also induced by the treatment (Childs et al. 2002). Few investigations have examined the responses between males and females to doxorubicin therapy in terms of systemic indicators of damage. Thus in this study we examined the responses of male and female Fischer 344 rats at 1 and 4 days following administration of a single dose of doxorubicin (10 mg kg-1). The University of Florida Institutional Animal Care and Use Committee approved all procedures prior to the onset of the study. Doxorubicin or saline was administered intraperitoneally. One or four days later, animals were anaaesthetized with an intraperitoneal injection of sodium pentobarbital (5 mg per 100 g body weight). Blood was collected into Vacutainer tubes containing ethylenediaminetetraacetic acid (K3EDTA; 8.4 mg per Vacutainer). Liver enzymes alanine transaminase (ALT) and aspartate transaminase (AST) were assayed in the plasma as markers of liver damage. Plasma creatine kinase (CK) and lactate dehydrogenase (LDH) levels were measured to evaluate muscle damage. As hypothesized, doxorubicin administration resulted in elevated liver enzyme activity compared with control animals in both males and females. To our surprise, we found no elevation in the muscle damage marker, CK, with the treatment. However, CK activities were significantly lower (P = 0.007) in females compared to males. A similar but non-significant trend was also apparent for LDH levels (P = 0.057). The dose of doxorubicin administered may have failed to inflict myocardial damage, but was sufficient to impose an insult on liver function. In summary, these findings demonstrate first, a sex difference in CK and LDH activities; and also reveal the influence of doxorubicin on liver function highlighted by the elevations in AST and ALT activities, which appear to be independent of sex.
Childs AC et al. (2002). Cancer Res 62, 4592-4598.
This work waas supported by American Heart Association, 0030334B.
Where applicable, experiments conform with Society ethical requirements