SIMVASTATIN AND ROSUVASTATIN IN THE PROTECTION AGAINST NSAID INDUCED GASTRIC MUCOSAL INJURY IN RATS & ROLE OF THEIR ANTIOXIDANT ACTIVITY

Matloub Samir Y. N; Manna Mohammed; Hussein Khalaf G

Authors

Matloub Samir Y. N Author
Manna Mohammed Author
Hussein Khalaf G Author

Keywords:

Statins, antioxidant activity, NSAID gastropathy

Abstract

Statins , the most effective drugs for the treatment of hyperlipidemia also exhibit other effects unrelated to their lipid lowering effects among which are antioxidant and anti-inflammatory actions .To investigate the gastroprotective effects of simvastatin and rosuvastatin against NSAID induced gastric mucosal damage and also to evaluate the influence of the antioxidant activity of those two chemically different statins on their gastrotoprotective effects.The study was conducted on 60 adult male albino rats, divided into 6 groups, the first served as a control received the vehicle , the second received 60mg/kg indomethacin orally. The third and fourth groups were pretreated with either simvastatin or rosuvastatin respectively in a dose of 20mg/kg orally for 2 weeks and then received indomethacin 60mg/kg one hour before the last dose of the statin. The role of nitric oxide (NO) in the gastroprotective effects of statins was investigated by using 20mg/kg intraperitoneal N^G-L-Arginine Methyl Ester (L-NAME) a nitric oxide synthase inhibitor which was given 30 minutes prior to the last dose of either simvastatin or rosuvastatin and this served as fifth and sixth groups respectively. The rats were then sacrificed after 6 hours and their stomachs were isolated and submitted to macroscopical assessment and for the measurement of the gastric prostaglandinE2 (PGE2), and myeloperoxidase (MPO). Rosuvastatin and simvastatin produced significant gastroprotective effects. Their protective effects were associated with marked decrease in MPO activity and increase in gastric PGE2 levels. However, the gastroprotective and antioxidant effects of the flurophenyl containing rosuvastatin were significantly better than that of simvastatin. L-NAME pretreatment decreased the protective effects of both rosuvastatin and simvastatin and this indicates the role of NO in their gastroprotective effects.