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Study of the statin effects on neuromuscular interaction in pregnant rats

Grant number: 21/03528-2
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): August 01, 2021
Effective date (End): April 30, 2022
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Selma Maria Michelin Matheus
Grantee:Kevin Silva Muller
Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Hypercholesterolemia is characterized as a key risk factor for cardiovascular diseases (DCs), which represent the main causes of death in the world. The biological synthesis of cholesterol is limited by the inhibition of the enzyme 3-hydroxy-3-methylglutaryl-CoA reductase, making statin drugs widely prescribed. Although statins are well tolerated, with their wide global use, clinical studies report frequent cases of adverse reactions (RA), with a high prevalence of mild neuromuscular disorders, but also rare severe episodes. The pathophysiology effects caused by RA on muscles and nerves are yet to be elucidated, and currently, there are no studies regarding changes for the neuromuscular junctions (JNMs). In addition, there are several factors that tend to increase the risk of gestational exposure to statins, showing the need of further studies in order to guarantee the safety and efficiency of those treatments. Thus, the objective of this study is to investigate the effects on the neuromuscular interaction by the exposure of pregnant Wistar rats to rosuvastatin and sinvastatin, targeting the sciatic nerve, the soleus muscle, and the associated JNMs. Thus, 15 pregnant Wistar rats (CEUA: 1115110620) will be randomly distributed in 3 groups (n=5): control, treated with distilled water and dimethyl sulfoxide, as a vehicle; simvastatin, at a dose of 62.5 mg/kg/day, diluted in a vehicle; and rosuvastatin, at a dose of 10 mg/kg/day, diluted in the vehicle. The treatment will be carried out daily, from the 8th day of gestation until the 20th day, by gavage. After the experimental period, the soleus muscles and the sciatic nerves will be collected and we will perform: morphological and morphometric analysis of the JNMs; morphological and morphometric analysis of muscle fibers (HE); morphological and quantitative analysis of the sciatic nerve; analysis and quantification of intramuscular collagen; protein quantification of nAChRs.

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