Chemotherapy-Induced Weakness and Fatigue in Skeletal Muscle: The Role of Oxidative Stress

Abstract

Significance: Fatigue is one of the most common symptoms of cancer and its treatment, manifested in the clinic through weakness and exercise intolerance. These side effects not only compromise patient's quality of life (QOL), but also diminish physical activity, resulting in limited treatment and increased morbidity. Recent Advances: Oxidative stress, mediated by cancer or chemotherapeutic agents, is an underlying mechanism of the drug-induced toxicity. Nontargeted tissues, such as striated muscle, are severely affected by oxidative stress during chemotherapy, leading to toxicity and dysfunction. Critical Issues: These findings highlight the importance of investigating clinically applicable interventions to alleviate the debilitating side effects. This article discusses the clinically available chemotherapy drugs that cause fatigue and oxidative stress in cancer patients, with an in-depth focus on the anthracycline doxorubicin. Doxorubicin, an effective anticancer drug, is a primary example of how chemotherapeutic agents disrupt striated muscle function through oxidative stress. Future Directions: Further research investigating antioxidants could provide relief for cancer patients from debilitating muscle weakness, leading to improved quality of life. Antioxid. Redox Signal. 15, 2543-2563.

Skeletal muscle loss after total gastrectomy, exacerbated by adjuvant chemotherapy

“…These combined results suggest that 5-FU might affect the loss of skeletal muscle, although the precise mechanism is unknown. Another anticancer agent, doxorubicin, has recently been shown to cause a catabolic response in skeletal muscle through oxidative stress by elevating the serum levels of inflammatory cytokines, especially tumor necrosis factor (TNF), resulting in a loss of skeletal muscle mass leading to weakness and fatigue [28]. One study reported delayed skeletal muscle dysfunction in survivors of childhood acute lymphoblastic leukemia, in which repeated administration of combination chemotherapy drugs (e.g., vincristine, glucocorticoids, doxorubicin, methotrexate, asparaginase) was strongly implicated [29].…”

Rehabilitation in patients with radically treated respiratory cancer: A randomised controlled trial comparing two training modalities

“…These treatments lead to a decrease in QoL, physical activity and enhance their morbidity [10]. Cancer-related fatigue (CRF), which is frequently reported by cancer patients, is defined as an unusual and persistent sense of tiredness, affecting both physical and mental capacity and is unrelieved by rest [35].…”

Parenteral vitamin C relieves chronic fatigue and pain in a patient with rheumatoid arthritis and mononeuritis multiplex secondary to CNS vasculitis

“…Vitamin C is a potent antioxidant and acts as a cofactor for numerous biosynthetic and regulatory enzymes in the body [5] , which may account for its observed effects in this case. Oxidative stress has been implicated in chronic fatigue syndrome [11] and chemotherapy-related fatigue [12] . Parenteral vitamin C has been shown to decrease both cancer -and chemotherapyrelated fatigue in cancer patients [2] .…”