Skeletal Muscle Mitochondrial Impairment in Cirrhosis-Induced Sarcopenia

Farshad, Omid; Ommati, Mohammad Mehdi; Yuzugulen, Jale; Alizadeh, Sahand; Mousavi, Khadijeh; Azarpira, Negar; Marhonian, Anahita; Jamshidzadeh, Akram; Heidari, Reza

doi:10.30476/tips.2020.87789.1067

Skeletal Muscle Mitochondrial Impairment in Cirrhosis-Induced Sarcopenia

Document Type : Original Article

Authors

Omid Farshad ¹

Mohammad Mehdi Ommati ²

Jale Yuzugulen ³

Sahand Alizadeh ³

Khadijeh Mousavi ¹

Negar Azarpira ⁴

Anahita Marhonian ⁵

Akram Jamshidzadeh ⁵

Reza Heidari ⁶

¹ Pharmaceutical Sciences Research Center, Shiraz university of Medical Sciences, Shiraz, Iran

² College of Life Sciences, Shanxi Agricultural University, Taigu, Shanxi 030801, Peoples&rsquo; Republic of China

³ Eastern Mediterranean University, Faculty of Pharmacy, Famagusta, North Cyprus, Turkey

⁴ Transplant Research Center, Shiraz University of Medical Sciences

⁵ Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

⁶ Shiraz University of Medical Sciences, Pharmaceutical Sciences Research Center

10.30476/tips.2020.87789.1067

Abstract

Cirrhosis-associated muscle mass loss or sarcopenia is a common complication (17-30% prevalence) in cirrhotic patients. However, the pathogenesis of this complication is poorly understood. Therefore, finding the mechanisms of sarcopenia could lead to the development of therapeutic strategies against this complication. In the current study, rats underwent bile duct ligation (BDL) surgery, and their skeletal muscle (gastrocnemius; GS) was isolated and assessed 28 and 56 days after BDL operation. Significant increase in biomarkers of oxidative stress, including reactive oxygen species (ROS) formation, lipid peroxidation, and increased oxidized glutathione (GSSG) levels were detected in the muscle of cirrhotic animals. Skeletal muscle tissue antioxidant capacity and reduced glutathione (GSH) were also significantly decreased in BDL rats. Moreover, deterioration of several mitochondrial indices, including mitochondrial depolarization, increased mitochondrial permeabilization, depleted ATP reservoirs, and decreased mitochondrial dehydrogenases activity, were evident in the GS isolated from cirrhotic rats. Based on these data, oxidative stress and mitochondrial impairment seem to play as primary mechanisms of cirrhosis-induced sarcopenia.

Keywords

Cell death

Cirrhosis

Energy crisis

Mitochondria

Muscle waste

Weakness