Effects of FOLFOX Chemotherapy Regimen and Exercise on Circulating Factors of Cardiovascular Disease in Mice
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Background: Cancer patients treated with FOLFOX are burdened by an array of side effects which can lead to early cessation of treatment. Specifically, FOLFOX is associated with increases in arterial stiffness, LV-stunning/weakness, both of which can lead to acute or chronic risk of developing heart failure and cardiovascular disease. To increase cardiovascular fitness and prevent FOLFOX cardiotoxicity exercise interventions have been proposed; however, a dearth of information exists on the timing and type of exercise that should be performed. Therefore, the purpose of this study was to investigate FOLFOX-induced alterations in circulating markers associated with cardiovascular damage 4-weeks post cessation of treatment, and to determine whether exercise can be utilized to mitigate increases in risk associated markers of cardiovascular disease. Methods: Male C57BL/6J mice (3 months) received 4 cycles (1 injection every 2 weeks) of FOLFOX (5-fluorouracil 30mg/kg, oxaliplatin 6mg/kg, leucovorin 90mg/kg), and were randomized to subgroups of sedentary (FOX, n=12), exercise trained (EXFOX, n=10), or PBS shams (CON n=11, EXCON n=9). Exercise training consisted of 14 sessions of treadmill exercise (18m/min, 5%grade, 15 minutes) during weeks 2-4 of the recovery period. Following completion of the treatment/exercise training, mice were sacrificed after a 12h overnight fast and a minimum of 48h after the last bout of exercise. Circulating markers were evaluated using Luminex Magpix multiplex analyzer (MILLIPLEX Mouse CVD1&CVD2 Bead Panel, Millipore Sigma, Burlington, MA, USA). Results: There was a significant effect of FOLFOX (p<0.05) for soluble endothelium selectin (sE-selectin), soluble platelet selectin (sP-selectin) and thrombomodulin. Significant effects of exercise (p<0.05) were found for soluble intercellular adhesion molecule-1 (sICAM-1), platelet endothelial cell adhesion molecule-1 (Pecam-1) and thrombomodulin. Conclusion: This preliminary investigation suggests there are systemic alterations in markers associated with cardiovascular disease following FOLFOX regimen occurring weeks after cessation of treatment. Low intensity exercise was unable to show any benefits in terms of preventing increases in these cardiovascular disease risk markers. These results promote further investigation into the impact these alterations may have on cardiac or vascular tissue following FOLFOX treatment. National Cancer Institue: R21-CA231131 & National Institutes of Health: R01HL14458 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
