Carnosine as a protective agent for skeletal muscle against doxorubicin-induced skeletal muscle dysfunction.

• Grant number: 26/01021-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2026
• End date: April 30, 2027
• Field of knowledge: Health Sciences - Nutrition - Nutrition Biochemistry
• Principal Investigator: Guilherme Giannini Artioli
• Grantee: Rafaela Abbade Garcia de Souza
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Carnosine is an endogenous dipeptide abundant in skeletal muscle, recognized for acting as an intracellular buffer, antioxidant, and for regulating calcium transients, playing a fundamental role in maintaining muscle contractile function. Evidence indicates that carnosine is capable of neutralizing reactive oxygen species and toxic aldehydes derived from lipid peroxidation, in addition to improving myofibrillar sensitivity to Ca²¿ and promoting muscle ionic homeostasis. Doxorubicin (DOX), a chemotherapeutic agent widely used in the treatment of various types of cancer, although highly effective, presents significant toxicity in non-tumor tissues, including skeletal muscle tissue. Its accumulation promotes oxidative stress, mitochondrial dysfunction, inflammation, and lipid peroxidation, resulting in atrophy, muscle weakness, and reduced functional capacity, effects that may persist even after the end of treatment. Given this scenario, this project aims to investigate whether carnosine exerts a protective effect against doxorubicin-induced skeletal muscle dysfunction. To this end, male Wistar rats with different intramuscular carnosine levels will be used, obtained through two experimental strategies: knockout animals for the Carns1 gene and ¿-alanine supplementation in wildtype animals. The animals will be treated with doxorubicin or vehicle, and the effects will be evaluated through analysis of ex vivo muscle contractile function, plasma markers of inflammation, muscle markers of oxidative stress, quantification of carnosine content, and morphological evaluation and typing of muscle fibers. (AU)