Rosuvastatin exposure in female Wistar rats alters uterine contractility and do not show evident (anti)estrogenic effects

Barros, Jorge Willian Franco de; Silva, Patrícia V.; Silva, Gustavo Venâncio da; Silva, Katiussia Pinho da; Borges, Cibele dos Santos; Mueller, André N.; Valencise, Lethícia; Pupo, André S.; Kempinas, Wilma De Grava

doi:10.1080/01480545.2021.1919139

Cited by 2 publications

(2 citation statements)

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“…Other studies have already demonstrated adverse effects of statins in smooth muscle, where exposures to this drug were related to alterations in uterine basal and induced contraction patterns in gravid and nongravid rats. 52 The response of treatment in striated muscles with glycolytic and/or intermediate fibers, as opposed to soleus muscle with oxidative fibers, should be investigated, as SAMS affects a wide range of skeletal muscles, from lower to upper limbs. 7 Furthermore, given our results, attention is also drawn to nonpregnant patients who undergo statin treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Given the wide variation in clinical practice with regard to dosages and period of treatment with statins after SAMS diagnosis, other experimental periods also need to be explored. Other studies have already demonstrated adverse effects of statins in smooth muscle, where exposures to this drug were related to alterations in uterine basal and induced contraction patterns in gravid and nongravid rats 52 . The response of treatment in striated muscles with glycolytic and/or intermediate fibers, as opposed to soleus muscle with oxidative fibers, should be investigated, as SAMS affects a wide range of skeletal muscles, from lower to upper limbs 7 …”

Section: Discussionmentioning

confidence: 99%

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Statin exposure during pregnancy promotes neuromuscular junction alterations in postpartum Wistar rats

et al. 2023

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Introduction/Aims The mechanisms that underlie the pathogenesis of statin‐associated muscle symptoms (SAMS) remain unclear. Pregnancy is associated with increased cholesterol levels. Statins may be useful during pregnancy, but their safety is uncertain. Hence, we investigated the postpartum effects of exposure to rosuvastatin and simvastatin during pregnancy in Wistar rats, targeting the neuromuscular structures. Methods Twenty‐one pregnant Wistar rats were divided into three groups: control (C) treated with vehicle (dimethylsulfoxide + dH20), simvastatin (S) 62.5 mg/kg/day, and rosuvastatin (R) 10 mg/kg/day. Gavage was performed daily from the gestational days 8 to 20. At weaning, the postpartum mother tissues were collected and subjected to morphological and morphometric analysis of the soleus muscle, associated neuromuscular junctions (NMJs), and the sciatic nerve; protein quantification; quantification of the cholesterol and creatine kinase in the serum; and intramuscular collagen analysis. Results An increase in morphometric parameters (area, maximum and minimum diameters, Feret diameter, and minimum Feret) was observed in NMJs from the S and R groups in comparison with the C group, and there was also a loss of common NMJ circularity. The number of myofibers with central nuclei was higher in S (17 ± 3.9, P = .0083) and R (18.86 ± 14.42, P = .0498) than in C (6.8 ± 2.6). Discussion Gestational exposure to statins induced postpartum NMJ morphology alterations in soleus muscle, which may be caused by the remodeling of clusters of nicotinic acetylcholine receptors. This may be associated with the development and progression of SAMS observed in clinical practice.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%