Effects of cisplatin on mitochondrial function and autophagy-related proteins in skeletal muscle of rats

Chiang

J cachexia sarcopenia muscle

et al. 2022

Background Cisplatin (CP) is a widely used chemotherapeutic drug with subsequent adverse effects on different organs and tissues including skeletal muscle loss and atrophy as the most common clinical symptoms. The molecular mechanism of cisplatin‐induced muscle atrophy is not clearly understood. However, recent significant advances indicate that it is related to an imbalance in both the protein status and apoptosis. Capsaicin (CAP) is one of the major ingredients in chilli peppers. It is a valuable pharmacological agent with several therapeutic applications in controlling pain and inflammation with particular therapeutic potential in muscle atrophy. However, the mechanisms underlying its protective effects against cisplatin‐induced muscle loss and atrophy remain largely unknown. This study aims to investigate capsaicin's beneficial effects on cisplatin‐induced muscle loss and atrophy in vitro and in vivo. Methods The anti‐muscle‐atrophic effect of capsaicin on cisplatin‐induced muscle loss was investigated using in vivo and in vitro studies. By using the pretreatment model, pretreated capsaicin for 24 h and treated with cisplatin for 48 h, we utilized a C2C12 myotube formation model where cell viability analysis, immunofluorescence, and protein expression were measured to investigate the effect of capsaicin in hampering cisplatin‐induced muscle atrophy. C57BL/6 mice were administered capsaicin (10, 40 mg/kg BW) as a pretreatment for 5 weeks and cisplatin (3 mg/kg BW) for seven consecutively days to assess muscle atrophy in an animal model for protein and oxidative stress examination, and the grip strength was tested to evaluate the muscle strength. Results Our study results indicated that cisplatin caused lower cell viability and showed a subset of hallmark signs typically recognized during atrophy, including severe reduction in the myotube diameter, repression of Akt, and mTOR protein expression. However, pretreatment with capsaicin could ameliorate cisplatin‐induced muscle atrophy by up‐regulating the protein synthesis in skeletal muscle as well as down‐regulating the markers of protein degradation. Additionally, capsaicin was able to downregulate the protein expression of apoptosis‐related markers, activated TRPV1 and autophagy progress modulation and the recovery of lysosome function. In vivo, capsaicin could relieve oxidative stress and cytokine secretion while modulating autophagy‐related lysosome fusion, improving grip strength, and alleviating cisplatin‐induced body weight loss and gastrocnemius atrophy. Conclusions These findings suggest that capsaicin can restore cisplatin‐induced imbalance between protein synthesis and protein degradation pathways and it may have protective effects against cisplatin‐induced muscle atrophy.

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Capsaicin alleviates cisplatin‐induced muscle loss and atrophy in vitro and in vivo

Chiang

J cachexia sarcopenia muscle

et al. 2022

Current Opinion in Clinical Nutrition &Amp; Metabolic Care

“…Cisplatin remains the most intensively studied individual compound [35][36][37][40][41][42][43][44][46][47][48]. Cisplatin suppresses protein synthesis via an Akt protein kinase B (Akt)-dependent mechanism, which leads to p70S6k1 dephosphorylation.…”

Section: Molecular Pathways Of Systemic Treatment-related Muscle Lossmentioning

confidence: 99%

Adverse effects of systemic cancer therapy on skeletal muscle: myotoxicity comes out of the closet

Klassen

Schiessel

Baracos

2023

Purpose of reviewSystemic cancer therapy-associated skeletal muscle wasting is emerging as a powerful impetus to the overall loss of skeletal muscle experienced by patients with cancer. This review explores the clinical magnitude and biological mechanisms of muscle wasting during systemic cancer therapy to illuminate this adverse effect. Emerging strategies for mitigation are also discussed.Recent findingsClinical findings include precise, specific measures of muscle loss over the course of chemotherapy, targeted therapy and immunotherapy. All these therapeutic classes associate with quantitatively important muscle loss, independent of tumor response. Parallel experimental studies provide understanding of the specific molecular basis of wasting, which can include inhibition of protein synthesis, proliferation and differentiation, and activation of inflammation, reactive oxygen species, autophagy, mitophagy, apoptosis, protein catabolism, fibrosis and steatosis in muscle. Strategies to mitigate these muscle-specific adverse effects of cancer therapy remain in the earliest stages of development.SummaryThe adverse side effect of cancer therapy on skeletal muscle has been largely ignored in the development of cancer therapeutics. Given the extent to which loss of muscle mass and function can bear on patients’ function and quality of life, protection/mitigation of these side effects is a research priority.

Korean J Physiol Pharmacol

“…Many clinical and animal studies indicate that exercise contribute to alteration to brain activation and/or damage. Recent studies reports that well-organized regular exercise and physical activity bring benefits to cisplatin toxicities-mediated side effects in the peripheral regions including skeletal muscle, renal, and heart [ 21 - 23 ] and emphasize the importance of consistent of exercise practice to potential protective effects. In contrast to, there is a limited amount of research on the effects of exercise on common CNS outcomes caused by chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

Exercise alleviates cisplatin-induced toxicity in the hippocampus of mice by inhibiting neuroinflammation and improving synaptic plasticity

Park,

Ko,

Han

2024

Self Cite

Chemotherapy-induced cognitive impairment is recognized as the most typical symptom in patients with cancer that occurs during and following the chemotherapy treatment. Recently many studies focused on pharmaceutical strategies to control the chemotherapy side effects, however it is far from satisfactory. There may be a need for more effective treatment options. The aim of this study was to investigate the protective effect of exercise on cisplatin-induced neurotoxicity. Eight-week-old C57BL6 mice were separated into three group: normal control (CON, n = 8); cisplatin injection control (Cis-CON, n = 8); cisplatin with aerobic exercise (Cis-EXE, n = 8). Cisplatin was administered intraperitoneally at a dose of 3.5 mg/kg/day. The Cis-EXE group exercise by treadmill running (14–16 m/min for 45 min daily, 3 times/week) for 12 weeks. Compared to the CON group, the cisplatin injection groups showed significant decrease in body weight and food intake, indicating successful induction of cisplatin toxicity. The Cis-CON group showed significantly increased levels of pro-inflammatory cytokines including IL-6, IL-1β, and TNF-α in the hippocampus, while the Cis-EXE group was significantly decreased in the expression of IL-6, IL-1β, and TNF-α. In addition, compared to the CON group, the levels of synapse-related proteins including synapsin-1 and -2 were significantly reduced in the Cis-CON group, and there was a significant difference between the Cis-CON and Cis-EXE groups. Antioxidant and apoptosis factors were significantly improved in the Cis-EXE group compared with the Cis-CON group. This study suggest that exercise could be meaningful approach to prevent or improve cisplatin-induced cognitive impairment.