Impact Of Creatine Supplement And Doxorubicin Therapy On Creatine Kinase Expression In Skeletal Muscle

Doxorubicin (Dox) is an effective and commonly used anticancer drug; however, it leads to several side effects which include myotoxicity. We reported previously that creatine (Cr) supplementation attenuates fatigue in rats receiving Dox, but the effects of Cr supplementation on Dox myotoxicity specific to the phosphocreatine system (creatine kinase, CK) have yet to be explored. PURPOSE: To examine the effects of Cr supplementation before Dox treatment on mitochondrial CK (MtCK) and cytosolic CK (CK-M) in the soleus (SOL) muscle. METHODS: Sixty male rats were randomly assigned to one of two four-week Cr feeding interventions (standard Cr diet or Cr loading diet) or a control diet (Con, n = 20). Rats in the standard Cr diet (Cr1, n = 20) were fed 2% Cr for four weeks. Rats in the Cr loading diet (Cr2, n = 20) were fed 4% Cr for one week followed by 2% Cr for three weeks. After 4 weeks of feeding, rats received either a bolus 15 mg/kg Dox injection or a saline injection as a placebo (Sal). Five days following injections, body mass (BM) and forelimb grip force (FG) were measured and SOL muscle was excised for analysis of MtCK and CK expression using Western blotting. RESULTS: A significant drug effect was observed for BM (p < 0.05). Post hoc testing revealed BM in Con+Dox (313 ± 9 g), Cr1 + Dox (292 ± 3 g), and Cr2 + Dox (294 ± 9 g) was significantly lower than Con+Sal (348 ± 10 g; P < 0.05). Additionally, a significant drug effect was observed for FG and Post hoc testing revealed FG force in Con+Dox (7 ± 1 N), Cr1 + Dox (6 ± 0.9 N), and Cr2 + Dox (7 ± 0.9) was significantly lower than Con+Sal (9 ± 0.4; P < 0.05). In contrast, no significant main effects or interactions were observed for MtCK and CK-M expression (P > 0.05). CONCLUSIONS: Doxorubicin treatment led to a decrease in BM and FG force, but Cr supplementation did not protect against these alterations. Creatine supplementation and a bolus dose of Dox in the current study did not promote phosphocreatine system alterations in SOL muscle suggesting that Cr and Dox may not directly impact on CK expression in slow oxidative muscle.