ADMINISTRATION OF H2 BLOCKERS IN NSAID INDUCED GASTROPATHY IN RATS: effect on histopathological changes in gastric, hepatic and renal tissues

Abstract

-Background -Nonsteroidal anti-inflammatory drugs induces gastric mucosal lesions because of its acidic properties.Ranitidine, an H 2 receptor antagonist, has proved beneficial in patients with gastric ulcers. Objective -The present study was performed to assess the effect of administering ranitidine in Nonsteroidal anti-inflammatory drugs (diclofenac, nimesulide) induced gastropathy, and their effect on the histopathology of stomach, kidney and liver. Methods -Diclofenac, nimesulide, and ranitidine were administered in doses of 2, 4, and 6 mg/kg, p.o. once daily for 14 days, and their effect on gastric volume, acidity, mean ulcer number, and gastric pH. In addition, histopathological examination was also performed on sections of stomach, kidney and liver.Results -Following the administration of diclofenac or nimesulide, all the gastric parameters were significantly altered as well as the histopathology of stomach, liver and kidney. In the control group, the renal sections showed normal glomeruli with no thickening of glomerular basement membrane, while in diclofenac alone, nimesulide alone, and ranitidine with nimesulide groups, the thickening of glomerular basement membrane was observed. These alterations were observed to be reversed in the ranitidine with diclofenac group. In the sections from the liver, the control group showed anastomosing plates and cords of cuboidal hepatocytes with round well stained nuclei and abundant cytoplasm. In the ranitidine with diclofenac, and ranitidine with nimesulide groups, mild dilatation of sinusoids is seen coupled with prominence of central vein. In the diclofenac alone and nimesulide alone groups, the proximal and distal convoluted tubules show mild focal tubular necrosis. In the gastric sections, the control group showed several folds forming villi, and the epithelial lining surface of the mucosa. In the ranitidine with diclofenac, and ranitidine with nimesulide groups, the duodenum showed scattered inflammatory cells composed predominantly of lymphocytes. In diclofenac alone and nimesulide alone group, the sections from the gastric areas showed partial necrosis and mild chronic inflammation respectively. Conclusion -The study, therefore, has provided therapeutic rationale towards simultaneous administration of H 2 receptor blocker ranitidine with diclofenac to be more beneficial as compared to ranitidine with nimesulide, to minimise the gastric intolerance of diclofenac in long term treatment of inflammatory conditions. HEADINGS -Diclofenac. Ranitidine. Histamine H 2 antagonist. Stomach diseases. Non-steroidal anti-inflammatory agents.

Metabolites profiling and pharmacokinetics of troxipide and its pharmacodynamics in rats with gastric ulcer

“…Additionally, according to the above calculation, absolute bioavailability following oral administration in the NCGIG and GUGIG were 70.51 ± 8.33% and 48.13 ± 4.90%, respectively. The absolute bioavailability in the GUGIG was significantly decreased (P < 0.01) compared with that in the NCGIG, possibly due to the slower distribution and reduced excretion in the GU rats 42,43 . This study of the pharmacokinetics of troxipide may provide accurate and detailed support for further development and clinical application of this drug in the near future.…”

Reduction of hepatotoxicity of nimesulide in mechanochemically obtained composition with disodium salt of glycyrrhizic acid

“…С одной стороны, показаны эффективность NIM как противоопухолевого агента у крыс линии Wistar [10], а также снижение выраженности жирового гепатоза при метаболическом синдроме у мышей линии C57BL/6J [11]. С другой стороны, гистоморфологическое исследование продемонстрировало, что применение NIM приводит к образованию очагов некроза в печени крыс Wistar [12]. Также обнаружено, что NIM провоцирует у крыс линии Wistar холестаз [13], а у крыс линии Sprague-Dowley и мышей линии Swiss повышает уровень печеночных трансаминаз в крови, вызывает гиперплазию печеночных протоков и дегенерацию гепатоцитов [14,15].…”

Role of Alginates Combined with Natural Extracts to Prevent the Gastric Acid-Related Damage

“…However, gastric mucosal perforation and bleeding are a major concern as well as the worst outcome of prolonged NSAID therapy [21]. NSAIDs are able to induce gastric mucosal lesions because of their acidic properties [22]. The mechanism behind gastric damage involves a highly acidic gastric environment that favors the migration of nonionized lipophilic NSAIDs into the epithelial cells [23].…”