Intramuscular and interstitial nitric oxide concentrations following doxorubicin administration in nude mice.

Abstract

The purpose of the present study was to examine intramuscular (IM) nitric oxide (NO) concentrations in the gastrocnemius (G) and quadriceps (Q) muscles as well as interstitial NO levels in the G of immunodeficient nude mice (n=6) following the administration of doxorubicin (10mg/kg). Muscles were collected at day 3 and 7 post injection and interstitial concentrations were determined using the microdialysis technique. Gastrocnemius IM concentrations of NO were increased (P<0.05) from control (626±18 μmol/kg dw) to 823 ±48 and 831±22 μmol/kg dw at day 3 and 7, respectively. Similarly, IM quadriceps concentrations of NO increased (P<0.05) from control (599±13 μmol/kg dw) to 738 ±18 and 756±46 μmol/kg dw at day 3 and 7, respectively. In contrast, G interstitial NO concentrations did not change (P>;0.05) from control values (14.0±2.5 μmol/l) for either collection period (day 3 = 16.4±1.7. day 7 = 15.7 ±1.6 μmol/l). These data clearly demonstrate that intramuscular NO concentrations are increased as a result of doxorubicin administration, and remain elevated for up to 7 days following initial dosing. Interestingly, doxorubicin administration did not alter interstitial NO concentrations suggesting that the effects of anthracyclines on stimulating NO production was isolated to intramuscular mechanisms. Overall, this study suggests that doxorubicin administration stimulates intramuscular NO production and may be a result of increased oxidative stress.Supported by NSERC