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SUMMARY AND CONCLUSIONThe highly selective Cox-II inhibitors could alleviate pain and inflammation but has less side effects than conventional NSAIDs. With Cox-II inhibitors gastrointestinal related toxicity have been significantly reduced. But in some other areas Cox-II specific inhibitors still have the classic problems associated with NSAIDs. Devil’s claw have been shown to reduce inflammation and pain associated with various types of arthritis. It has been shown to cause no GIT, cardiac or renal affection.The aim of the present study, was to evaluate and compare some of the toxicological hazards of both rofecoxib and harpagophytum procumbens extract (herpago), also to evaluate the extent of improvement that occur in both groups after their discontinuation (follow up period).The study was conducted on 170 adult albino rats of both sexes weighing approximately (120-150 gm) divided into 5 groups.Group I (-ve control group): consisted of 30, each rat was given no medications to evaluate the basic parameters.Group II [+ve control group one (Gum acacia group)]: consisted of 30 rat, each rat was gavaged with 2 C.C of Gum acacia suspension once daily for 6 weeks.Group III [+ve control group two (distilled water group)]: consisted of 30 rat, each rat was gavaged with 2 C.C. of distilled water for 6 weeks.Group IV (eofecoxib group): consisted of 40 rat, each rat was gavaged with 1.8 mg rofecoxib/rat (double human therapeutic dose) once daily for 6 weeks.Group V (gerpago group): consisted of 40 rat, each rat was gavaged with 86.4 mg herpago/rat (double human therapeutic dose) once daily for 6 weeks.Methods:At the end of the first six weeks: ten rats from rofecoxib group and herpago group were used for blood pressure measuring and another ten rats from each group were used for biochemical and histopathological studies. fifteen rats from each control group were used for blood pressure measuring and another fifteen from each group were used for biochemical and histopathological studies.The remaining rats of both rofecoxib and herpago groups were left for another 6 weeks without drug administration for follow up. At the end of this period the rats were examined as above.The main findings of the present study were as follow:Group I (-ve control group), group II (+ve control group one), and group III (+ve control group two) showed no abnormal findings without statistically significant difference between them so we used the results of the –ve control group to compare it with those of rofecoxib and herpago groups as regard:(I) Blood pressure measuring:In rofecoxib group an increase in systolic and diastolic blood pressure was detected with a significant difference when compared with -ve control group (P<0.001).After 6 weeks of follow up (6 weeks after stoppage of drugs administration) the systolic and diastolic blood pressure of rofecoxib group decrease to the control level and gave no significant difference when compared with the –ve control group (P>0.05).In herpago group the systolic and diastolic blood pressure increase to the control level and gave no significant difference when compared with the –ve control group (P>0.05).II- Biochemical changes:As regard rofecoxib group there was an increase in serum Na+, K+, and creatinine levels with a decrease in pH and HCO3- with a statistically significant difference when compared with the –ve control group (P<0.001).On the other hand, herpago group showed no abnormal findings in the above mentioned 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 –ve control group (P>0.05).Serum K+ and creatinine levels decrease, but the level of improvement didn’t reach to the control level and gave significant difference when compared with the –ve control group (P<0.05).Serum HCO3- and pH increase, but the level of improvement didn’t reach the control level and gave significant difference when compared with the –ve control group (PIII- Histopathological study of:(1) The heart:As regard rofecoxib group microscopical examination of the cardiac sections showed ischemic changes with atrophy of cardiac muscles.While 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 thickeness and length.(2) The kidney:As regard rofecoxib group histopathological examination of the kidney showed severe affection of the kidney in the form of renal papillary necrosis, acute and chronic tubulo-interstitial nephritis with interstitial oedema and inflammatory cell infiltrate. On the other hand, herpago group showed no histopathological abnormalities.After 6 weeks of follow-up histopathological examination of the kidney in the rofecoxib group showed incomplete recovery.(3) The gastrointestinal tract:As regard rofecoxib group histopathological examination of the stomach and small intestine showed different degrees of affection varies from oedema of lamina propria and vascular congestion to loss of superficial epithelium (erosion) and peptic ulcer. On the other hand, herpago group showed no histopathological abnormalities after 6 weeks of follow up in rofecoxib group partial healing of erosions and ulcers occur and the mucosa regained its normal thickness.CONCLUSIONAccording to the above mentioned results we can conclude that, rofecoxib is more toxic than herpago through inducing an increase in both systolic and diastolic blood pressure, producing an increase in serum Na+, K+ and creatinine levels and decrease in HCO3- level and blood pH, in addition to its ability to produce histopathological changes in the heat, kidney and GIT and the above mentioned effects were partially reversible after discontinuation of the drug.RECOMMENDATIONSOn the light of the results of the present study we recommended the following guidelines:(1) Usage of rofecoxib in advanced renal diseases, is not recommended, also it is contro-indicated in severe heart failure, inflammatory bowel disease and in patients with hepatic impairment.(2) Dosage adjustment in elderly is necessary. Therapy with rofecoxib should be initiated in the lowest dose.(3) Rofecoxib as a selective Cox-II inhibitor produced toxic effects on the heart in adult albino rats so its use should be minimized to avoid its toxic effects in human and it should be withdrawn from the markets.(4) Herpago as a herbal agent was proved to have the same anti-inflammatory effect as rofecoxib but more safe than it. So its use should be encouraged to avoid serious side effects produced by rofecoxib.(5) Herpago was proved to be a safe drug till now but further studies to evaluate any toxic effects with different doses and duration are needed.
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