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Abstract 94 SUMMARY In the present study. the acute and short term chronic toxicity of two anti-inflammatory drugs (Piroxicam and pirprofen) given alone or in combination with the anabolic compound (methyl androstenolone acetate) were investigated. Besides, valuable knowledge about their toxicities were obtained. Acute toxicity studies: The results of the study revealed the following results: Piroxicam was more toxic to female rats than males on acute basls. since the LD~o and LDs4 of females were about one third those of males. Its acute toxicity was not antagonized by the anacolic drug. Pirprofen was equally toxic to male, female, adult dnd lmmature rats. Its acute toxicity was reduced by about 25% in adult male rats by the anabolic drug. Short term chronic toxicity studies: These stud ies were done on 100 adult normal male albino rats divided into 10 equal groups each comprising 10 rats. The obtained results indicated that the anabolic .._---- ---- -------------- drug (met yl androstenolone acetate) reduced the mortality rate of p”rprofen on chronic administration by 5 folds. On the other hand. the anabolic agent had not effect in the case of piroxicam. ~~- _._~- 95 The two antl-lntlamrnatory drugs reduced the growth rate. while the body weight was constant. The anabolic drug imp::-oved the harmful effect of pirprofen but this effect wa3 not observed in case of piroxicam. Both the anti-inflammatory drugs caused a noticeable reduction in the weight of the spleen but the other internal organs were constant. This effect was not modified by the anabolic drug. Serum bio·:::hemica1 studies i.. Serwn glucose level antiinflammatory drugs. Serwn total proteins, albumin, globulin and albumin to globulin ratios were not modified In response to chronic t~xicity of the anti-inflammatory drugs. was not affected by the Piroxicam (1.8 and 5.4 mg/kg) as well as pirprofen high dose level markedly elevated serum bilirubin by 71.25%. 82.5% and 44.94%, respectively. This effect was -- ---~---- ---- -----.-.,--,,-~ ’1 96 abolished by the anabolic drug treatment. Serum transaminase (GOT and GPT) activity was not pathologically affected by the antiinflammatory drugs. Both the antiinflammatory drugs induced marked increment in serum alkaline phosphatase activity. The effect was more pronounced in case of pirprofen (82.33%) than piroxicam. The anabolic was able to antagonize the effect of piroxicamthan that of pirprofen. The increase of serum alkaline phosphatase along with the increment of serum bilirUbin is an indicator of drug induced cholestatic jaundice. The renal excretory function was not effected by the two antiinflammatory drugs, since serum creatinine and urea were not elevated. However. serum urea level was decreased to 60.46% in response to pirprofen. The effect was related to slight depression in liver function and this amount of-nitrogenous compound may be directed to protein biosynthesis. ThIS erfect was not corrected by l:he anabo lic agent. The estimation of serum prostaglandin confirmed that the anabolic compound may enhance the medic41 effects of the antiinflammatory drugs or at least shall not -----~--- - --- - ---- -, -- -, ---” -- _. -- - - ----- _._--- ---------- -------~-~ 97 anta.gonize them. Liver biochemical studiest Piroxicam elevated liver triglyceride content. This result indicates that a degree of liver fatty deposition occurred. This effect was not antagonised by the anabolic drug. Hepatic ribonucleic acid content was elevated in response to bothpiroxicam and pirprofen by 17% and 19%, respectively. ThIS effect is probably related to the increment requirement of proteins needed for drug protein bindIng and biosynthesis or ~nzymes. Tnerefore. the protein percentage of liver has been increased. The anabolic antagonized the effect of the piroxicam while did not affect on the p~rproten. Hepatic DNA was not affected by the antIInflammatory drugs. Liver lysosomal studies indica.ted that chronIC tOXicity of both piroxicam and pirprofen is related to excessive labilization of lysosomes. This toxic effect was minImized to a great extent by the anabolic drug. Bloodha,matoloqical studies: Blood haematologlcal studies showed that both piroxIcam and pirprofen caused a.grdnulocytosis phenomenon. -- -_.. -- --~--- -- ---.- ---- -- -- --- - - -- _.- ._---- --- -- ---- - -- ------- 98 This toxic effect was not accompanied by any degree of anaemia. ; The anabo Ir c agent was not able to correct this effect. Finally. it is recorrmended that determination of serum bilirubin and haematological examination of leucocytes should be done during prolonged therapy with piroxicam and pirprofen. The concurrent administrat-ion of anabolic steroid is also very much advisable. Future studies are recommended to investigate the use ot anabollcS in combatting toxicity of other types of drugs and its action mechanism. -- - - ---- -- ---- --- -- _. -- ..- - -- - -- - - ._- -- - -- ._-- - _. -_.-._----- |