Cisplatin-Induced Skeletal Muscle Dysfunction: Mechanisms and Counteracting Therapeutic Strategies

Abstract

Among the severe side effects induced by cisplatin chemotherapy, muscle wasting is the most relevant one. This effect is a major cause for a clinical decline of cancer patients, since it is a negative predictor of treatment outcome and associated to increased mortality. However, despite its toxicity even at low doses, cisplatin remains the first-line therapy for several types of solid tumors. Thus, effective pharmacological treatments counteracting or minimizing cisplatin-induced muscle wasting are urgently needed. The dissection of the molecular pathways responsible for cisplatin-induced muscle dysfunction gives the possibility to identify novel promising therapeutic targets. In this context, the use of animal model of cisplatin-induced cachexia is very useful. Here, we report an update of the most relevant researches on the mechanisms underlying cisplatin-induced muscle wasting and on the most promising potential therapeutic options to preserve muscle mass and function.

Ergogenic Effect of BCAAs and L-Alanine Supplementation: Proof-of-Concept Study in a Murine Model of Physiological Exercise

“…This multidisciplinary assessment allowed us to obtain valuable information about the efficacy and safety of BCAAs and ALA supplementation in physiological conditions. Importantly, this may represent the first step for a future application of this supplementation in various muscle-wasting conditions, such as those occurring in inherited neuromuscular disorders or secondary cachectic, atrophic, and sarcopenic states [31,32].…”

Supplementary Oral Anamorelin Mitigates Anorexia and Skeletal Muscle Atrophy Induced by Gemcitabine Plus Cisplatin Systemic Chemotherapy in a Mouse Model

“…Given anamorelin was well-tolerated and significantly increased lean body mass, anamorelin might be a treatment option for patients with cancer anorexia and cachexia. However, only few studies investigated the clinical potential of supplementary oral anamorelin to mitigate the negative adverse events induced by cancer chemotherapy [ 25 , 28 ].…”

Hexarelin exerts neuroprotective and antioxidant effects against hydrogen peroxide-induced toxicity through the modulation of MAPK and PI3K/Akt patways in Neuro-2A cells

“…Ghrelin has been demonstrated to protect several cell types such as adipocytes [37], osteoblast [38], cardiomyocytes and endothelial cells [39] by inhibiting apoptotic stimuli. As well, ghrelin has been shown to have protective effects in vivo, in rats exposes to status epilepticus [40] or in rat model of cisplatin-induced cachexia [4]. To investigate the molecular pathways involved in hexarelin neuroprotection, we investigated the expression of MAPKs (ERK and p38) and PI3K/Akt.…”

“…In addition to its endocrine effects, GHS also target peripheral tissues; to illustrate, GHS improve muscle function in several pathological conditions by inhibiting the apoptosis pathway, reducing NO release and counteracting inflammation [3,4].…”