Analysis of the Effects of Different Doses and Classes of Statins on the Neuromuscular Interaction of Sleep-Deprived Rats

• Grant number: 23/13817-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2024
• End date: March 31, 2025
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Selma Maria Michelin Matheus
• Grantee: Gabrielly Nicoli da Silva Pereira
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Cardiovascular diseases (CVDs) continue to be one of the leading causes of death on a global scale.Medications from the statin class are widely used in medical practice due to their action on systemic cholesterol. However, their frequent use in clinical practice and research studies has been strongly associated with recurring cases of statin-associated muscle symptoms (SAMS), ranging from mild neuromuscular disorders to severe episodes. The underlying pathophysiological mechanisms of SAMS are not yet fully understood, and further studies are needed to elucidate these mechanisms, especially involving neuromuscular junctions (NMJs), structures that we have already shown to be affected by treatment. Studies indicate that individuals suffering from insomnia have disrupted metabolic functions and an imbalanced energy balance. The resulting effects of this disorder are similar to those observed in relation to other well-recognized contributors to cardiovascular diseases, and the number of people affected by such conditions is growing. Therefore, this study aims to investigate the effects of different doses and classes of statins on structures involved in the neuromuscular interaction in sleep-deprived rats. A total of 64 Wistar rats will be divided into 8 groups: Control (C), with no intervention; sleep deprivation (P), treated with the vehicle for statins (whipped cream); sleep deprivation groups + atorvastatin, receiving a daily single dose of 4.2 mg/kg (A-) or 20 mg/kg (A+) of the drug, homogenized in the vehicle (whipped cream); sleep deprivation groups + simvastatin, receiving a daily single dose of 4.2 mg/kg (S-) or 20 mg/kg (S+), homogenized in the vehicle (whipped cream); and sleep deprivation groups + rosuvastatin, receiving a daily single dose of 4.2 mg/kg (R-) or 20 mg/kg (R+). Sleep deprivation will be conducted daily using the multiple platform method, from 2 PM to 8 AM for 45 consecutive days. After the experimental period, blood, the sciatic nerve, and EDL muscles will be collected for morphological and morphometric analysis of NMJs, muscle and nerve fibers, intramuscular collagen quantification, functional evaluation using the gait test, and biochemical tests for CK enzyme and serum cholesterol.