Published in:
01-02-2016 | Original Article
Protective Effects of Simvastatin Against Alendronate-Induced Gastric Mucosal Injury in Rats
Authors:
Nathalia S. Carvalho, Mônica M. Silva, Renan O. Silva, Lucas A. D. Nicolau, Thiago S. L. Araújo, Douglas S. Costa, Nayara A. Sousa, Luan K. M. Souza, Pedro M. G. Soares, Jand Venes R. Medeiros
Published in:
Digestive Diseases and Sciences
|
Issue 2/2016
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Abstract
Background
It has been reported that simvastatin, a statin commonly prescribed for its anti-inflammatory and antioxidant effects, has gastroprotective effects in indomethacin and ethanol-induced gastric ulcers. However, the effects of simvastatin on alendronate-induced gastric mucosal injury remain unexplored.
Aim
This study investigated the use of simvastatin for the treatment of alendronate-induced gastric ulcers in rats.
Methods
Female rats were pretreated with vehicle or simvastatin (20 and 60 mg/kg p.o.). After 1 h, the rats received alendronate (50 mg/kg p.o.). Simvastatin was administered once daily for 7 days, and from the fourth day of simvastatin treatment, alendronate was administered once daily for 4 days. On the final day of treatment, 4 h after alendronate administration, animals were euthanized, their stomachs were removed, and gastric damage was measured. Samples of the stomach were fixed in 10 % formalin immediately after their removal for subsequent histopathological assessment. Unfixed samples were weighed, frozen at −80 °C until assayed for glutathione (GSH), malondialdehyde (MDA), and cytokine levels and myeloperoxidase (MPO) activity. A third group was used to measure mucus and gastric secretion.
Results
Pretreatment with simvastatin prevented alendronate-induced macroscopic gastric damage and reduced the levels of MDA and GSH, TNF-α and IL-1β, MPO activity, and mucus levels, in the stomach.
Conclusions
This study demonstrates the protective effects of simvastatin against alendronate-induced gastric ulceration. Maintenance of mucosal integrity, inhibition of neutrophil activity, and reduced oxidative stress associated with decreased gastric acidity may explain the gastroprotective effects of simvastatin.