Effect Of Long Term Administration Of Some Non Steroidal Anti-inflammatory Drugs On The Chromosomal Pattern:

Hamdi Ahmed Mohamed

The present work aimed to study the effect of chronic administration of some currently used NSAIDs, namely,indomethacin, piroxicam and diclofenac on the rate ofmitosis and on the chromosomal pattern of bone marrowcells of albino rat.Bone marrow samples used through this study wereobtained from 200 albino rats. They were divided into 4equal groups, each comprising 50 animals. In the firstgroup, the animals were given indomethacin at a dose of 3mg/kg daily. In the second group, the animals were givenpiroxicam at a dose of 1 mg/kg daily. In the third group,the animals were given d{clofenac at a dose of 2 mg/kgdaily. The three groups were given the drugs for 10,20,30,45 and 60 days. In the fourth group, the animals were give5% gum arabic aqueous solution daily ·for 10,20,30,45 and60 days and were used as controls. Observations of thecell kinetics and cytogenetic changes of the bone marrowcells were carried out on 10 rats from each group after10,20,30,45 or 60 doses of drug administration. The methodof preparing met~ase spreads from bone marrowaccording to Palmer et a1. (1972) and Giemsawas usedstain wasprepared according to the method described by Genest andAuger (1963).For each rat, 500 cells were counted and the percentageof the transformed cells were calculated. For chromosomalanalysis, 50 metaphases were examined for thepresence of any chromosomal a~omalies either structural ornumerical, and the results were tabulated and tested usingthe student t test. ·The results of the present studyrevealed the following :1- The mean transformed cell percentage in control samolesafter 10,20,30,45 and 60 days were 24.28%±1.5623,23.96%±2.0336, 23.66%±1.5762, 24.36%±1.8808 and 24.06%±1.8055respectively and there was no significant statisticaldifference between them (P·<0.05).2- The mean transformed cell percentage in indomethacinsamples after 10,20,30,45 and 60 days were 23.96% ±1.7489, 22.98% ± 2.147, 22.2% ± 1.9067, 20.78% ± 1.6357and 17.96% ± 2.2125 respectively and there was a highstatistically significant reduction in t~e samplesexamined 45 and 60 .days after drug administration (P<0.001). On the other hand, the samples examined 10;20and 30 days after the drug administration revealed nosignificant statistical· difference ·in comparison withthe control (P <0.05)•3- The mean transformed cell percentage in piroxicamsamples after 10,20,30,45 ~nd 60 days were 23.8%±1.917,22.96%±2.1602, 21.94%±2.1338, 21.22%±1.6l79 and 18.26%±2.2671 respectively and there was a high statisticallysignificant reduction in the samples examined 45 and 60days after drug administra~ion (P <0.001). On the otherhand, the samples examined 10,20 and 30 day after thedrug administration revealed no significant statisticaldifference in comparison with the control (P <0.05).4- The mean transformed cell percentage in diclofenacsamples after 10,20,30,45 and 60 days were 24.44%--±1.7074, 23.28%±2.0221, 22.66%±2.0773, 21.68% ± 1.9078and 18.64% ± 2.3626 respectively and there was a highstatistically significant reduction in the samples.examined 45 and· 60 days.after the drug administration(P <0.001). On the other hand, the samples examined10,20 and 30 days after the drug administrationrevealed no significant statistical difference incomparison with the control (P <0.05).5- The total numbers of chromosomal aberrations in 500examined cells for the controls including structuralanomalies, aneuploidy and polyploidy were as follows :a- After 10 daysb- After 20 daysc- After 30 days .. 2 4 8d- After 45 days 2 3 . 8e- After 60 days. : 2 : 3 : 96- The total number of chromosomal aberrations for theindomethacin samples including structural anomalies,·aneuploidy and polyploidy were as follows :a- After 10 daysb- After 20 days2 : 4 73 3 : 9-84-c- After 30 days: 4 : 5 :.11d- After 45 days 7: 9 : 15e- After 60 days 9 13 : 197- The total number of chromosomal aberrations for thepiroxicam samples including structural anomalies, aneuploidyand polyPloidy were as follows :a- After 10 days : 2 : j : 7b- After 20 days : 3 : 3 8c- After 30 days : 4 5: 10d-.After 45 days.: 8 : 9 .:14e- After 60 days 10: 11 : 188- The total number of chromosomal aberrations for thediclofenac samples including structural anomalies,aneuploidy and polyploidy were as follows :a- After 10 days : 2 3 8b- After 20 days : 3 4: 7c- After 30 days : 3 : 5 : 9d- After 45 days : 5 : 7 : ’13e- After 60 days 9·::U: 179- The chromosomal aberrations in the studied groupsexamined 10,20 and 30 days revealed no significantstatistical difference ~n comparison ,with the control(P <0.05). On the other hand, the three drugs causedsignificant increase in chromosomal anomalies, structuraland numerical, after drug administration for 45and 60 days as compared to normal untreated controls (P<0.05).from the previous results it may be concluded thatthe slgn!iicant decrease of transformed cells occurred 45and 60 days after drug administration for indomethacin,piroxicam and diclofenac and the chromosomal aberrationsfound were statistically significant after these therapeuticdaily administrations for 45 and 60 days. So, one mayassume that the tested drugs exhibit their effect after 45and 60 days of administration.In addition, the choice of any of the drugs will beaccording to the sensitivity of the disease in questionand/or according to the accomodation of the patient to ~heside effects since all drugs had nearly the same effect onthe cell··kinetics and the dhromosomal· pattern.