Comparative study between the toxic effects of rofecoxib and harpagophytum procumbens extract on adult albino rats

ABSTRACT

The highly selective cyclo- oxygenase II [COX-II] inhibitors could alleviate pain and inflammation and have fewer side effects than conventional non-steroidal anti-inflammatory drugs [NSAIDs]. Herpagophytum Procumbens has been shown to reduce inflammation and pain associated with various types of arthritis. The aim of this work was to perform a comparison between the toxic effects of Rofecoxib and Harpagophytum Procumbens [herpago] on adult male albino rats. This study included 170 adult male albino rats divided into 5 groups. Group I, II and III were used as control groups [-ve control group, Gum acacia group and distilled water group] each consisted of 30 rats remained for 6 weeks. Group IV [rofecoxib group] consisted of 40 rats, each rat was gavaged with 1.8 mg rofecoxib/rat [double human therapeutic dose] once daily for 6 weeks. Group V [herpago group] consisted of 40 rats, each rat was gavaged with 86.4 mg herpago/rat [double human therapeutic dose] once daily for 6 weeks. At the end of six weeks ten rats from rofecoxib [IV] and herpago [V] groups and fifteen rats from each control group [I, II and III] were used for blood pressure measuring. Another ten rats from groups IV and V and fifteen rats from I, II and Ill were used for biochemical and histopathological studies. The remaining rats of both groups IV and V were left for another 6 weeks without drug administration for follow up. At the end of this period the follow up rats were examined as above. Groups I, II and III showed no abnormal findings without statistically significant difference between them [P>0.05]. In rofecoxib group an increase in systolic and diastolic blood pressures [SBP, DBP] were detected with a significant difference when compared with -ve control group [P<0.001], while herpago group showed a decrease in SBP and DBP with a statistically significant difference when compared with the -ve control group [P<0.001]. After 6 weeks of follow up, the SBP and DBP of rofecoxib and herpago groups showed no significant difference when compared with the -ve control group [P>0.05]. After 6 weeks of treatment there were an increase in serum Na+ and K+ levels with a decrease in serum pH and HCO3- with a statistically significant difference in rofecoxib group when compared with the -ve control group [P<0.001]. Herpago group showed no abnormal findings in the above mentioned biochemical, parameters. Six weeks after the discontinuation of rofecoxib administration the Na+ level returned to its control level and gave no significant difference when compared with the -ye control group [P>0.05]. Serum K+, HCO3- and pH levels improved but didn't reach to the control level and gave significant difference when compared with the -ve control group [P<0.05]. Macroscopically, no abnormal findings in the heart gastro- intestinal tract [GIT] were detected in all tested groups. With rofecoxib group, microscopical examination of the cardiac sections showed ischemic changes with atrophy of cardiac muscles. Herpago group showed no histopathological abnormalities on microscopical examination. After 6 weeks of follow up histopathological examination of the heart in rofecoxib group showed disappearance of the ischaemic changes. The cardiac muscles regain its normal thickness and length. Histopathological examination of the stomach and small intestine of rofecoxib group showed different degrees of affection varies from edema of lamina propria and vascular congestion to loss of superficial epithelium [erosion] and peptic ulcer. Herpago group showed no histopathological abnormalities in the GIl. After 6 weeks of follow up in rofecoxib group partial healing of erosions and ulcers occur and the mucosa regained its normal thickness. It could be concluded that rofecoxib is more toxic than herpago and its toxic effects were partially reversible after its discontinuation