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

Doxorubicin (DOX), a powerful anthracycline antibiotic commonly used to treat a wide variety of cancers, is associated with the production of reactive oxygen species that cause oxidative damage, resulting in cardiac dysfunction. Components of dairy may have protective effects against DOX-induced cardiac damage. Kefir is a naturally fermented milk product containing antioxidants, probiotic bacteria, and yeast in addition to the protective components of dairy. We explored the effects of dietary milk and kefir on DOX-induced cardiotoxicity in rats. We used singly housed, 10-wk-old male Sprague Dawley rats assigned to 1 of 3 isocaloric diets, control (CON n = 24), milk (MLK, n = 24), or kefir (KEF, n = 24), with equivalent macronutrient profiles. After a 9-wk dietary intervention, all animals were given either a bolus injection (15 mg/kg) of DOX (CON-DOX n = 12; MLK-DOX n = 12, KEF-DOX n = 12) or saline (CON-SAL n = 12; MLK-SAL n = 12; KEF-SAL n = 12). Body weight, grip strength, echocardiographic evaluation of cardiac geometry, and cardiac function were evaluated using echocardiography at 5 d postinjection and data were analyzed using ANOVA. Survival at d 5 post-DOX injection was 92 and 100% in KEF-DOX and MLK-DOX, respectively, and 75% in CON-DOX. By the last week of the dietary intervention, and just before injection with saline or DOX, CON weighed significantly (14%) more than the MLK and KEF. The DOX treatment resulted in significant reductions in body weight; however, we found no diet × drug interactions. The DOX treatment reduced peak grip strength compared with SAL; when compared with pre-injection measures, MLK-DOX rats did not experience a significant reduction in peak grip strength compared with CON-DOX and SAL-DOX rats. Heart mass in MLK and KEF was significantly higher when compared with CON. In summary, 9 wk of milk or kefir ingestion resulted in lower body size and higher heart mass after DOX treatment. Additionally, MLK preserved peak grip strength after DOX treatment, whereas KEF or CON did not. We observed no consistent protective effects with respect to heart dimensions and function. These findings suggest that long-term milk or kefir ingestion may be helpful in optimizing health before and during doxorubicin treatment.

Effects of treadmill training on combined goserelin acetate and doxorubicin-induced osteopenia in female rats.

OBJECTIVES: This study examined individual and combined effects of the cancer treatments goserelin acetate (GA) and doxorubicin (DOX) on bone and determined if treadmill running (TM) provides osteoprotection. METHODS: Ten-week-old female Sprague-Dawley rats were randomly assigned to sedentary (SED) or TM groups. SED received GA, DOX, combined GA and DOX (GA+DOX), or placebo and maintained normal cage activity. TM received GA, DOX, GA+DOX, or placebo and participated in a progressive motorized treadmill protocol. After 8 weeks, tibiae were evaluated using micro computed tomography. RESULTS: Negative drug effects were observed in cancellous bone (bone volume/tissue volume, trabecular number, trabecular thickness, trabecular spacing; P<0.05). An additive bone volume/tissue volume and trabecular spacing effect was observed in SED GA+DOX (vs. SED+GA and SED+DOX, P<0.05) but not in TM GA+DOX (vs. TM+GA and TM+DOX, P>0.05). Negative drug effects were observed in cortical bone (cross-sectional volume, cortical volume, marrow volume; P<0.05), but combined GA+DOX did not exacerbate these effects. Additionally, there were no protective cortical bone effects observed in TM. CONCLUSIONS: Combined GA+DOX exacerbates cancellous osteopenia in the tibia, and treadmill running provided only minor protection.

Androgen deprivation therapy and cardiac function: effects of endurance training.

PURPOSE: This study examined the effects of an 8-week androgen deprivation therapy treatment using Zoladex and an endurance training regimen on cardiac function. METHODS: Male Sprague-Dawley rats received either Zoladex or placebo. Animals remained sedentary or endurance trained during the drug treatment period. On day 57, ex vivo cardiac function was analyzed. RESULTS: Hearts from sedentary animals receiving Zoladex possessed significant cardiac dysfunction. However, hearts from exercise trained rats receiving Zoladex possessed cardiac function values similar to those from hearts from placebo animals. CONCLUSIONS: An 8-week treatment with Zoladex promoted cardiac dysfunction. Endurance training during Zoladex treatment protected against this cardiac dysfunction.