Silibinin Alleviates Muscle Atrophy Caused by Oxidative Stress Induced by Cisplatin through ERK/FoxO and JNK/FoxO Pathways.
Meng-Yi ChiHong ZhangYa-Xian WangXi-Peng SunQuan-Jun YangCheng GuoPublished in: Oxidative medicine and cellular longevity (2022)
Cisplatin (DDP), a widely used chemotherapeutic drug in cancer treatment, causes oxidative stress, resulting in cancer cachexia and skeletal muscle atrophy. This study investigated the effects and activity of silibinin (SLI) in reducing DDP-induced oxidative stress and skeletal muscle atrophy in vivo and in vitro. SLI alleviated weight loss, food intake, muscle wasting, adipose tissue depletion, and organ weight reduction induced by DDP and improved the reduction of grip force caused by DDP. SLI can attenuated the increase in reactive oxygen species (ROS) levels, the decrease in Nrf2 expression, the decrease in the fiber cross-sectional area, and changes in fiber type induced by DDP. SLI regulated the ERK/FoxO and JNK/FoxO pathways by downregulating the abnormal increase in ROS and Nrf2 expression in DDP-treated skeletal muscle and C2C12 myotube cells. Further, SLI inhibited the upregulation of MAFbx and Mstn, the downregulation of MyHC and MyoG, the increase in protein degradation, and the decrease of protein synthesis. The protective effects of SLI were reversed by cotreatment with JNK agonists and ERK inhibitors. These results suggest that SLI can reduce DDP-induced skeletal muscle atrophy by reducing oxidative stress and regulating ERK/FoxO and JNK/FoxO pathways.
Keyphrases
- signaling pathway
- skeletal muscle
- induced apoptosis
- pi k akt
- oxidative stress
- insulin resistance
- reactive oxygen species
- cell cycle arrest
- diabetic rats
- dna damage
- weight loss
- poor prognosis
- adipose tissue
- transcription factor
- cross sectional
- cell death
- ischemia reperfusion injury
- physical activity
- cell proliferation
- binding protein
- type diabetes
- body mass index
- high glucose
- high fat diet
- hydrogen peroxide
- drug induced
- mouse model
- small molecule
- endothelial cells
- metabolic syndrome
- adverse drug
- gastric bypass