ADMINISTRATION OF H2 BLOCKERS IN NSAID INDUCED GASTROPATHY IN RATS: effect on histopathological changes in gastric, hepatic and renal tissues.
BACKGROUND
Nonsteroidal anti-inflammatory drugs induces gastric mucosal lesions because of its acidic properties. Ranitidine, an H2 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.


CONCLUSIONS
The study, therefore, has provided therapeutic rationale towards simultaneous administration of H2 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.
Department of Pharmacology, Vardhaman Mahavir Medical College and Safdarjung Hospital, New Delhi, India, Vardhaman Mahaveer Open University, Department of Pharmacology, Vardhaman Mahavir Medical College, Safdarjung Hospital, New Delhi , India.
Sachin
S
Manocha
Department of Pharmacology, ESIC Dental College and Hospital, Rohini, New Delhi, India, Department of Pharmacology, ESIC Dental College and Hospital, New Delhi , India.
Dushyant
D
Lal
Department of Pharmacology, Dr. A.L.M.P.G. Institute of Basic Medical Sciences, University of Madras, Taramani, India, University Of Madras, Department of Pharmacology, Institute of Basic Medical Sciences, University of Madras, Taramani , India.
Subramanian
S
Venkataraman
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D004008:Diclofenac / Q000494:pharmacology*; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D011899:Ranitidine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control*; D013449:Sulfonamides / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D006635:Histamine H2 Antagonists; D013449:Sulfonamides; D004008:Diclofenac; D011899:Ranitidine; C012655:nimesulide