Endurance training reduces exercise-induced acidosis and improves muscle function in a mouse model of sickle cell disease

Sickle cell disease (SCD) mice (Townes model of SCD) presented exacerbated exercise-induced acidosis and fatigability as compared to control animals. We hypothesize that endurance training could represent a valuable approach to reverse these muscle defects. Endurance-trained HbAA (HbAA-END, n = 10), HbAS (HbAS-END, n = 11) and HbSS (HbSS-END, n = 8) mice were compared to their sedentary counterparts (10 HbAA-SED, 10 HbAS-SED and 9 HbSS-SED mice) during two rest exercise recovery protocols during which muscle energetics and function were measured. In vitro analyses of some proteins involved in muscle energetics, pH regulation and oxidative stress were also performed. Exercise-induced acidosis was lower in HbSS-END mice as compared to their sedentary counterparts during both moderate (p < 0.001) and intense (p < 0.1) protocols. The total force production measured during both protocols was higher in trained mice compared to sedentary animals. In vitro analyses revealed that enolase/citrate synthase ratio was reduced in HbSS-END (p < 0.001) and HbAS-END (p < 0.01) mice compared to their sedentary counterparts. In addition, malondialdehyde concentration was reduced in trained mice (p < 0.05). In conclusion, endurance training would reverse the more pronounced exercise-induced acidosis, reduce oxidative stress and ameliorate some of the muscle function parameters in SCD mice.