Muscle damage induced by eccentric exercise: involvement of mitochondria and interactions with statin myotoxicity

• Grant number: 11/51800-1
• Support type: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): March 01, 2012
• Effective date (End): February 28, 2015
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal researcher: Roger Frigério Castilho
• Grantee: Tiago Rezende Figueira
• Home Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 11/50400-0 - Mitochondrial energy metabolism, redox state and functionality in cell death and cardiometabolic and neurodegenerative disorders, AP.TEM

Abstract

Eccentric exercise-induced muscle damage (EIMD) is the most common muscle trauma associated with exercise. EIMD arises when unaccustomed exercise tasks involving eccentric muscle contractions are performed. EIMD generally leads to: i) delayed onset muscle soreness; ii) loss of joint range of motion; iii) muscle edema; iv) contractile dysfunction; v) muscle inflammation; vi) and a variety of metabolic alterations. These changes evolve from myocyte structural injury (sarcomere disarrangement, cell membrane rupture, etc.) that is imposed by eccentric muscle contractions. It was demonstrated that cellular calcium overload is a primary abnormality in EIMD etiology. Also, EIMD promotes calcium accumulation within mitochondria. It is widely appreciated that mitochondrial calcium overload may lead to opening of mitochondrial permeability transition pore (MPT), which can disrupt mitochondrial integrity and function, promote cell death and tissue damage. Our hypothesis is that calcium-induced MPT plays a role in EIMD and in associated abnormalities such as mitochondrial respiratory depression. Therefore, we aim at investigating whether MPT inhibition by means of pharmacological tools (cyclosporin A, an inhibitor of MPT; Ru360, an inhibitor of mitochondrial calcium uptake) can abrogate EIMD and the associated mitochondrial changes in rats. Additionally, we will approach the known harmful interaction (i.e. higher prevalence of statins side effects) between eccentric exercise and statins, a class of drugs that possess mitochondrial and muscular toxicity. (AU)

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FIGUEIRA, TIAGO R.; FRANCISCO, ANNELISE; RONCHI, JULIANA A.; DOS SANTOS, GUILHERME R. R. M.; DOS SANTOS, WILLIAM; TREBERG, JASON R.; CASTILHO, ROGER F. NADPH supply and the contribution of NAD(P)(+) transhydrogenase (NNT) to H2O2 balance in skeletal muscle mitochondria. Archives of Biochemistry and Biophysics, v. 707, AUG 15 2021. Web of Science Citations: 0.

FIGUEIROA, EVELLYNE DE OLIVEIRA; ARANDA-SOUZA, MARY ANGELA; VAREJAO, NATHALIA; ROSSATO, FRANCO APARECIDO; PEREIRA COSTA, RUTE ALVES; FIGUEIRA, TIAGO REZENDE; NASCIMENTO DA SILVA, LUIS CLAUDIO; CASTILHO, ROGER FRIGERIO; VERCESI, ANIBAL EUGENIO; DOS SANTOS CORREIA, MARIA TEREZA. pCramoll and rCramoll lectins induce cell death in human prostate adenocarcinoma (PC-3) cells by impairment of mitochondrial homeostasis. TOXICOLOGY IN VITRO, v. 43, p. 40-46, SEP 2017. Web of Science Citations: 1.

CHWEIH, HANAN; CASTILHO, ROGER F.; FIGUEIRA, TIAGO R. Tissue and sex specificities in Ca2+ handling by isolated mitochondria in conditions avoiding the permeability transition. Experimental Physiology, v. 100, n. 9, p. 1073-1092, SEP 1 2015. Web of Science Citations: 10.

MICHELINI, LUIZ G. B.; FIGUEIRA, TIAGO R.; SIQUEIRA-SANTOS, EDILERIE S.; CASTILHO, ROGER F. Rotenone exerts similar stimulatory effects on H2O2 production by isolated brain mitochondria from young-adult and old rats. Neuroscience Letters, v. 589, p. 25-30, MAR 4 2015. Web of Science Citations: 4.

ARANDA-SOUZA, MARY A.; ROSSATO, FRANCO A.; COSTA, RUTE A. P.; FIGUEIRA, TIAGO R.; CASTILHO, ROGER F.; GUARNIERE, MIRIAM C.; NUNES, ERIKA S.; COELHO, LUANA C. B. B.; CORREIA, MARIA T. S.; VERCESI, ANIBAL E. A lectin from Bothrops leucurus snake venom raises cytosolic calcium levels and promotes B16-F10 melanoma necrotic cell death via mitochondrial permeability transition. Toxicon, v. 82, p. 97-103, MAY 2014. Web of Science Citations: 20.