Vitamin C Protects Against Doxorubicin‐Induced Muscle Oxidative Stress

Abstract

Introduction Doxorubicin, has been used as a chemotherapeutic agent, however, it is also associated with significant cardiotoxicity related to an increased oxidative stress (OS). Recent studies have shown that doxorubicin also induces skeletal muscle atrophy in preclinical models. Vitamin C (VC), which presents antioxidant properties, has been used as a pharmacological approach against cardiac toxicity. Nonetheless, the effects of vitamin C on doxorubicin‐induced skeletal muscle atrophy are still unknown. Objective Evaluate the effects of VC on OS parameters in skeletal muscle of rats exposed to doxorubicin. Methods Male Wistar rats divided into 4 groups (C: Control. VC: Vitamin C. D: Doxorubicin and VCD: VC+Dox, n=8‐10/group). Dox was administered in six doses of 2.5 mg/kg, for 3 weeks to obtain a cumulative dose of 15 mg/kg. VC was administered daily (50 mg/kg) orally for six weeks, starting one week before treatment with Dox. The gastrocnemius was weighed and homogenized for OS analysis: antioxidant profile (catalase [CAT], superoxide dismutase [SOD], glutathione peroxidase [GPx] and non‐enzymatic antioxidant capacity [FRAP]), pro‐oxidant (NADPH oxidase, hydrogen peroxide [H2O2], nitrites) and cell damage (protein and lipid oxidation [LPO]). Results Dox reduced the gastrocnemius weight, on the other hand VC prevented it (C: 1.74±0.03; VC: 1.55±0.18; D: 0.99±0.06 and VCD: 1.23±0.06 g). There were no differences in CAT, FRAP, NADPH and nitrites between studied groups. D group showed increased concentration of H2O2 compared to C and VC groups; which was not observed in the VCD group (C: 5.33±0.39; VC: 4.30±1.47; D: 8.72±1.58 and VCD: 3.66±0.73 μM H2O2). SOD was higher in the VCD group compared to the others (C: 8.29±0.61; VC: 8.38±0.48; D: 9.94±0.61 and VCD: 10.38±0.28 USOD/mg protein). GPx was higher in VC and VCD compared to C group and lower in D compared to C and VCD group (C:0.007±0.002; VC: 0.012±0.002; D: 0.009±0.001 and VCD: 0.011±0.001 nmol/mg protein). Protein oxidation was lower in C group compared to the others (C: 3.63± 0.93; VC: 6.98±0.74; D: 5.69±0.49 and VCD: 5.98±0.29 nmol/mg protein). However, LPO was higher in D group compared to C and VC groups, and lower in VCD group compared to D group (C: 342±122; VC:364±153; D: 998±131 and VCD: 389±50 cps/mg protein). Conclusion Vitamin C protects against doxorubicin‐induced skeletal muscle atrophy and oxidative stress, suggesting a potential approach to management cardio functional disorder in patients under doxorubicin treatment.