The Effect of Iron on Skeletal Muscle Atrophy in Chronic Kidney Disease

Abstract

Introduction and aims: Iron is an essential trace metal for all living organisms. However, excessive iron catalyzes the formation of highly toxic hydroxyl radicals via the Fenton reaction. Skeletal muscle atrophy is often observed in chronic kidney disease (CKD) patients. However, the molecular mechanism of skeletal muscle atrophy in CKD has remained unclear. The purpose of this study was to determine whether iron is involved in CKD-related skeletal muscle atrophy. Methods In this study, 8-weeks-old C57BL/6J mice were divided into 2 groups: vehicle-treated group and adenine-injected group. Results The skeletal muscle in CKD mice showed elevated expression of the muscle atrophy-related E3 ubiquitin ligases, atrogin-1 and muscle ring finger-1, along with reduced skeletal muscle mass. CKD mice showed an increase in the iron content of the skeletal muscle and serum ferritin levels. The expression of transferrin receptor, an iron import receptor, and ferroportin, an iron export transporter, were downregulated in the skeletal muscle from CKD mice. The expression of ferritin heavy chain and ferritin light chain were upregulated in the skeletal muscle from CKD mice. CKD mice showed increased oxidative stress in the skeletal muscles. Conclusions These results suggest that iron accumulation-mediated oxidative stress has the potential to accelerate skeletal muscle atrophy in CKD.