Milk and kefir maintain aspects of health during doxorubicin treatment in rats

摘要

Doxorubicin (DOX), a powerful anthracycline antibioticcommonly used to treat a wide variety of cancers,is associated with the production of reactive oxygenspecies that cause oxidative damage, resulting in cardiacdysfunction. Components of dairy may have protectiveeffects against DOX-induced cardiac damage.Kefir is a naturally fermented milk product containingantioxidants, probiotic bacteria, and yeast in additionto the protective components of dairy. We exploredthe effects of dietary milk and kefir on DOX-inducedcardiotoxicity in rats. We used singly housed, 10-wk-oldmale Sprague Dawley rats assigned to 1 of 3 isocaloricdiets, control (CON n = 24), milk (MLK, n = 24),or kefir (KEF, n = 24), with equivalent macronutrientprofiles. After a 9-wk dietary intervention, all animalswere given either a bolus injection (15 mg/kg) of DOX(CON-DOX n = 12; MLK-DOX n = 12, KEF-DOXn = 12) or saline (CON-SAL n = 12; MLK-SAL n= 12; KEF-SAL n = 12). Body weight, grip strength,echocardiographic evaluation of cardiac geometry, andcardiac function were evaluated using echocardiographyat 5 d postinjection and data were analyzed usingANOVA. Survival at d 5 post-DOX injection was 92and 100% in KEF-DOX and MLK-DOX, respectively,and 75% in CON-DOX. By the last week of the dietaryintervention, and just before injection with saline orDOX, CON weighed significantly (14%) more thanthe MLK and KEF. The DOX treatment resulted insignificant reductions in body weight; however, wefound no diet × drug interactions. The DOX treatmentreduced peak grip strength compared with SAL; whencompared with pre-injection measures, MLK-DOX ratsdid not experience a significant reduction in peak gripstrength compared with CON-DOX and SAL-DOXrats. Heart mass in MLK and KEF was significantlyhigher when compared with CON. In summary, 9 wk ofmilk or kefir ingestion resulted in lower body size andhigher heart mass after DOX treatment. Additionally,MLK preserved peak grip strength after DOX treatment,whereas KEF or CON did not. We observedno consistent protective effects with respect to heartdimensions and function. These findings suggest thatlong-term milk or kefir ingestion may be helpful in optimizinghealth before and during doxorubicin treatment.