Keywords : Imatinib
Iraqi Journal of Veterinary Sciences,
The safety region of imatinib, and markedly its role in testicular toxicity has been studied in a controversial manner in current years. This study was designed to address the repercussion of administration of groups of pups with imatinib mesylate (at neonatal or infantile periods) using histological analysis of their testes in several end points and in adulthood. Intact pups (albino-male) exposed to 200 mg/kg of oral imatinib once daily at neonatal and early infantile period on PND 1 to PND10 (for ten days). All experiments performed with age and weight matched control which administered with Distilled water. Pups were into categorized into 4 subgroups, according to the ages of euthanasia: 15 days postpartum (PND); 40days postpartum; 70 days postpartum and 140 days postpartum. The histological analysis was conducted in blind fashion after staining with (Harris Hematoxylin and Eosin stain. Ten randomly selected testicular sections from each rat were analyzed qualitatively and quantitavely. In addition, Johnsen' scores were used to analyze the effect of drug on spermatogenesis. Data were recorded and value is considered as significant when it P<0.05. imatinib induced several alterations in testicular sections in comparison with those of control group including significant reduction of number of peripheral germ cells layers at PND 15. Different histological changes were more frequent in tissues obtained from rats euthanized at PND 40 and PND70. Quantitative changes were also noticed as diminishing of seminiferous tubular diameter of the, height of epithelial layer especially at PND70. Partial recovery was noticed in sections of rats euthanized at PND140. In conclusion, imatinib does affect the histology of rat testis markedly, but this effect is reversible once the drug administration is ceased. That may provide a benefit for the specialists in planning and addressing of the fertility associated issues in young patients -throughout their reproductive periods- who are being on imatinib treatment for gastrointestinal tumors and chronic myeloid leukemia (CML).
Iraqi Journal of Veterinary Sciences,
The safety zone of imatinib, and specifically its relevancy to organ toxicity, has been discussed dialectically in current years. Oxidative stress may be one of the causes of imatinib -mediated toxicity. This study aimed to examine the possible role of co-enzyme Q10 in ameliorating the adverse effect of imatinib on the testicular histology of male albino rats -if it is present. Twenty-eight male Albino rats were used randomly assigned to 4 experimental groups: Group 1 includes 40-45 days aged rats (n=8) which were gavage a dose of 200 mg/kg/day/30 days of imatinib mesylate. Group 2 includes age matched control rats which were administered with distilled water(n=4). Group 3 includes eight rats were received Q10, 50mg/kg, alone, Q10-sorb capsule of 50 mg given with the same schedule. Group 4. Includes eight rats were co administrated orally with 50 mg/kg of Q10+200 mg/kg of imatinib (once/day/30days). Euthanizing of animals with ether 24 hours after the final dose was done. Testes of rats from each experimental group were obtained. The tissues processed and stained by routine histological method. Histological sections of testes's rats treated with 200mg/Kg of imatinib revealed different testicular lesions compared to those of control group (P<0.05). Six 6(75%) of these sections revealed degenerated tubules, detached Sertoli cells, and apoptosis. These histological sections also showed thick tunica albuginea, seminiferous tubules with thick basement membrane. sometimes only a few of Sertoli cells were appeared in histological sections of imatinib treated rats. Mean Johnsen’s scores in these sections was 5.1±0.1 (P˂0.001). Features of retained spermatid were also noticed in some sections. There was significant reduction in both seminiferous tubular diameter and the epithelial height of histological sections of group 2(P˂0.001) with mean of 140.2±3.2µm and 14.8±1.1 µm respectively. Moreover, the number of Sertoli cells/ seminiferous tubule were significantly increased (P˂0.001), with mean of 27.4±0.2 and Leydig cell number is also significantly raised with mean of 7.5±0.5. In conclusion, treatment of peripubertal rats with imatinib induced several testicular alterations (including Sertoli cells) in comparison to control rats indicated that this drug is a gonadotoxic agent as it affects the quality and quantity of spermatogenesis. An Ameliorating effect of co-enzyme Q10 co-administration on imatinib-induced testicular toxicity was concluded.