Comparative Adverse Effects Of Cox-1 and Cox-2 Inhibitors in Rat Liver: An Experimental Study."

Abstract

The non-steroidal anti-inflammatory drugs (NSAIDs) do not reverse the disease process, but they provide much needed relief from pain and inflammation by inhibiting cyclooxygenase (COX) enzyme mediating the inflammatory pathway. NSAIDs cause number of death as a result of upper gastrointestinal damage. These agents also have unwanted effects on lower bowel, lungs, kidney and cardiovascular symptom. Coxibs are selective inhibitor of cyclooxygenase (COX)-2 and spares the COX-1 induced side effects i.e. gastric ulceration. Therefore in present study we compared the adverse effects of diclofenac sodium (diclo) a non-selective NSAID and valdecoxib (valde), a selective NSAID attherapeutic and subtherapeutic doses. Histological and biochemical changes of liver were observed. Beside that gross examination of the stomach mucosa for ulceration along lesser curvature too observed. For liver functions we estimated serum aspartate aminotransferase (AST), alknine aminotransferase (ALT), lactate dehydrogenase (LDH) and alkaline phosphatase (ALP). Experiment was carried out by administration of drugs for period of 30 days. Liver sections of diclo &; valde groups showed histological changes, which were more prominent with therapeutic dose of valde. The biochemical changes, subtherapeutic dose of diclo showed increase in ALP only. On the other hand subtherapeutic dose of valde showed significant changes in AST, high significant changes in LDH &; ALP Whereas therapeutic doses of diclo and valde showed highly significant increase in hepatic biochemical parameters i.e. AST, ALT, ALP, LDH.Thus it may conclude that higher doses of COX-1&;2 inhibitors can lead to acute hepatitis and other hepatic complications.