PHARMACODYNAMIC INFLUENCE OF VITAMIN E AND ESOMEPRAZOLE ON GASTRO PROTECTION IN PYLORUS LIGATION INDUCED ULCERS IN RATS
NITIN M, MOHAN REDDY U*
Department of Pharmacology,
H.K.E.S’s, Matoshree Taradevi Rampure Institute of Pharmaceutical Sciences,
Sedam Road, Gulbarga- 585 105, Karnataka
Gastric ulcer is one of the most prevalent gastrointestinal disorders, which affects approximately 5-10% of people during their life. The present study was aimed to find out the pharmacodynamic influence of vitamin E and esomeprazole and their combination on gastro intestinal parameters in pylorus ligation induced ulcers in rats in single and multiple dose studies. Various parameters were studied in pylorus ligation induced ulcer model viz. gastric volume, pH, total acidity, free acidity, and ulcer index.The antiulcer effect of the combination of vitamin E 0.9 mg/200 g and esomeprazole 0.54 mg/200 g b.w orally was compared with the reference standard esomeprazole 0.54 mg/200 g b.w orally. The ulcer index was calculated and other biochemical parameters of gastric juice were estimated. The ulcer index of combination showed significant (P < 0.05) reduction while other biochemical parameters like volume, pH, free acidity and total acidity of gastric juice showed highly significant (P < 0.001) reduction when compared to control and standard esomeprazole.
Reference Id: PHARMATUTOR-ART-1358
Peptic ulcer disease is one of the most common gastrointestinal disorders, which causes a high rate of morbidity particularly in the population of non-industrialized countries1. Peptic ulcer disease occurs mainly due to consumption of NSAIDs, infection by H. pylori, stress or due to pathological condition such as Zollinger- Ellison Syndrome.Peptic ulcer may occur due to an imbalance between offensive and defensive factor. Major offensive factors are acid, pepsin, Helicobacter pylori and bile salts. Defensive factors mainly involve mucus-bicarbonate secretion and prostaglandins2. Among the various causes of gastric ulceration reactive oxygen species (ROS) plays an important role in the pathogenesis of a wide variety of clinical disorders and gastric damage. They attack essential cell constituents, such as proteins, lipids and nucleic acids, leading to the formation of toxic compounds. Besides ROS the other fundamental factor in the pathogenesis is the hypersecretion of gastric acid. Therefore, the control of acid secretion and neutralization of ROS may be essential for the treatment of peptic ulcer. This can be done by combination therapy of antioxidants with antisecretory drugs like esomeprazole.
One of the main cause of peptic ulcer can be H. pylori bacterial infection; however some ulcers are caused by the long-term use of nonsteroidal anti-inflammatory agents (NSAIDs), like aspirin and ibuprofen, and because of stress due to socio-economic problems, etc. In a few cases, cancerous tumours in the stomach or pancreas also cause peptic ulcers3. Free radicals are unpaired electrons released during oxidative stress and play important role in pathogenesis of peptic ulcer as they cause cellular damage. Antioxidants are used to neutralize these free radicals which function by accepting or donating an electron to eliminate the unpaired electron4.
Esomeprazole is a new proton pump inhibitor and is the S-isomer of racemic omeprazole.The oral bioavailability of esomeprazole is approximately 89% with a dose of 40 mg, and the half-life is approximately 1.5 hours.Esomeprazole is a safe and effective proton pump inhibitor. It is effective in the treatment of peptic ulcer disease and gastroesophageal reflux disease5.Vitamin-E iswell known antioxidant that defends against cell damage.
Hence an attempt was being made to study the efficacy of combination of the same antioxidant ( Vit-E) with esomeprazole to treat peptic ulcers.
MATERIALS AND METHODS
Pure drug samples of esomeprazole and vitamin E were procured from Aurobindo Pharmaceuticals (Hyderabad) and Cipla pharmaceuticals (Mumbai) as gift samples. The dose calculations were extension of human dose based on body surface area6.
Albino rats (Wistar strain) of either sex weighing 180-250 g were used for the study. They were procured from central animal house, M.R.Medical College, Gulbarga. They were kept in the departmental animal house at 26 ± 2°C relative humidity 55 ± 15%, in light and dark cycles of 12 and 12 h, respectively for 10 days before and during the experiments. Animals were provided with standard rodent pellet diet (Golden feeds, Delhi) with water ad libitum. The experimental protocol was approved by the Institutional Animal Ethical Committee (IAEC) (HKE COP / IAEC / 35 / 2010 -11/CPASEA).
Evaluation of anti -ulcer activity
One animal model (Pyloric ligation) was employed to evaluate the Anti-ulcer activity of Vitamin E and esomeprazole and their combination in single and multiple dose studies.
1) Pyloric ligation model7
In pylorus ligation induced ulcer model, the rats were divided into 4 groups of 6 animals each. The animals of Group I were treated with vehicle and the animals of Group II were treated with standard, i.e., esomeprazole 0.54 mg/200 g b.w orally. The animals of Group III were treated with vitamin E 0.9 mg per 200 g b.w orally. Group lV were treated with esomeprazole and vitamin E i.e., 0.54 mg and 0.9 mg per 200 g b.w orally with an interval of 30 min between them.
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