Gastrocnemius Mass Is Lower 28 Days After Recovery From A Cycle Of Cisplatin In Mice

Platinum-based chemotherapeutic agents, such as cisplatin, are widely employed as a primary treatment modality for various cancer types. Despite their efficacy, cisplatin\u27s mechanism of action involves inducing DNA damage in cells, leading to pronounced acute and long-term side effects. One well established side effect is rapid loss in muscle mass. However, very little is known about the long-term effects of chemotherapy treatment on muscle size. PURPOSE: of this study was to analyze the long-term effects of cisplatin on muscle mass recovery. We hypothesized that cisplatin would have a negative long-term effect on muscle recovery. METHODS: 5-6 month-old CD2F1 mice were divided into two groups receiving injections of either Cisplatin (Cis) or Vehicle (Veh); n = 10 per group. A clinically relevant chemotherapy cycle was completed by a once weekly injection of 5mg/kg body weight of cisplatin for four weeks. Veh mice received an equal volume of saline. Following the cycle, mice recovered in their cage for 28 days and then hindlimb muscles were taken. Data were analyzed using independent t-test and presented as mean ± standard error. RESULTS: The gastrocnemius mass was significantly lower (p=0.008) in cisplatin-treated mice (139.20 ± 4.98) compared to the vehicle-treated group (147.50 ± 2.26). Conversely, the soleus did not show a significant difference (p=0.756) between Cis (9.90 ± 0.46) and Veh (10.10 ± 0.44) groups. Similarly, the Plantaris did not demonstrate a significant difference (p=0.950) in Cis treatment (18.65 ± 0.57) compared to Veh (18.65 ± 0.54). CONCLUSION: These data indicate a diminished ability of the gastrocnemius, the primary hindlimb flexor, to recover after a bout of cisplatin drug treatment. Further research is needed to better understand the mechanisms behind muscle specific differences and failed muscle mass recovery in the gastrocnemius

Cisplatin Blunts Muscle Hypertrophy in Exercise Trained Mice

Cisplatin is a chemotherapeutic agent known to cause skeletal muscle atrophy and cachexia; however, the long-term effect of cisplatin on skeletal muscle adaptations to exercise remains unclear. PURPOSE: The purpose of this study was to assess if prior administration of a clinically relevant cycle of cisplatin blunts exercise adaptations in response to 8 weeks of exercise training. METHODS: Female CD2F1 mice, n = 7-8/group, were treated with 5 mg/kg of cisplatin, or vehicle, once per week for 4 weeks, then given a 4-week washout. Afterwards, mice were singly housed and subjected to either progressive weighted wheel running (PoWeR) for 8 weeks or remained sedentary in their cages. RESULTS: Differences between groups were examined using a two-way ANOVA. Body weight was consistent between group (average range: 27.0 g to 27.5 g), and muscle mass was nearly identical in sedentary vehicle- and cisplatin-treated mice. In vehicle-treated mice, 8 weeks of PoWeR caused whole-muscle hypertrophy in the soleus (+28% normalized wet weight) and plantaris (+18% normalized wet weight) muscle when compared to sedentary mice. This was accompanied by an elevation in muscle fiber cross-sectional area (CSA) by 18% and 14% in the soleus and plantaris, respectively. PoWeR trained mice treated with cisplatin displayed signs of anabolic resistance, which included significantly lower soleus (-22%) and plantaris (-19%) weight when compared to vehicle treated. Muscle fiber CSA was also lower in the soleus (-15%) and plantaris (-13%) muscles compared to vehicle. Interestingly, the exercise-mediated glycolytic-to-oxidative fiber-type transition was the same between the groups. CONCLUSION: Collectively, our data indicate that previous exposure to cisplatin leads to anabolic resistance in mice. Additional analysis and follow-up studies are required to elucidate the mechanisms driving this response