US EPA

1567643 

Journal Article 

Evaluation of thalidomide against indomethacin-induced small intestinal damage and systemic toxicity in rats 

Silva, MA; Rao, VS; Souza, CM; Neves, JCS; Menezes, DB; Santos, FA; Andrade, GM 

2012 

1 

Biomedical Research
ISSN: 0970-938X
EISSN: 0976-1683 

23 

1 

125-133 

WOS:000306059400020 

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 anti-inflammatory agent with TNF-alpha 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