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Clinical use of indomethacin although efficacious in suppressing pain, fever and inflammation is frequently associated with deleterious effects on gastrointestinal, hematological and renal systems that limit its therapeutic use. This study examined in rats whether thalidomide, a known antiinflammatory agent with TNF-α inhibitory, immunomodulatory and anti-angiogenic properties could ameliorate indomethacin-induced toxicity that includes lethality, hematological and biochemical changes in blood, as well as the small intestinal damage. Wistar male rats in groups were treated orally with indomethacin (5, 10, and 20 mg/kg), thalidomide (100 and 200 mg/kg, either alone or in combination with indomethacin 5 mg/kg) once daily during 5 days. Lethality was assessed during this period and on day-5 blood samples were collected to examine the hematological and biochemical changes. The animals were then sacrificed and the small intestine removed for histological analysis. Results demonstrated that treatment with thalidomide did not improve the survival rate of indomethacin-treated rats. However, indomethacin-associated leucopenia, decrease in red blood cells, hemoglobin, and hematocrit as well as the elevation in plasma fibrinogen, serum AST and ALP, small intestinal lesion score, and the peritoneal liquid myeloperoxidase level were significantly suppressed by thalidomide treatment. In conclusion, the study suggests that thalidomide has the potential of ameliorating the toxic effects of indomethacin to a large extent, possibly by virtue of its anti-inflammatory properties.
Indomethacin toxicity, thalidomide, plasma fibrinogen, small intestinal damage