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Abstract Anaesthetic drugs are nowadays used on a large scale in surgical operations as well as in other various medical purposes. Of these drugs, ketalar (ketamine) has been gaining a wide profile of application, especially in children for the management ofpediatric surgery, beside its utilization to patients suffering from severe pains after surgery. It is true that this drug has contributed positively to such prospects, but it is also equally true that it has been frequently incriminated for many adverse consequences evoked in the body as a result of its application. These facts have stimulated several researches to deal with the impacts of this drug on several body organs. But nonetheless, one of the essential body organs, namely the testis has not apparently received equal attention in such aspects. Thus, the present work was designed aiming at assessing and evaluation of any possible cytotoxic alteration in the mammalian testis under the effect of this drug. To complete the picture, the chromosomes were also planned to be taken into consideration in this investigation. The experimental animal selected for these experiments is the white mouse (Mus musculus). In general, the main points of this study is thereafter outlined: • External (Morphological) symptoms which could appear on the drug- treated mice. • Histology of the control testis (for the sake of comparison). • Histopathological changes of the testis examined post treatment with this anaesthetic. • Cytogenetical follow up of the chromosomes of bone- marrow cells, comprising two main aspects: + Normal karyotypes of the chromosomes of both male and female mice. + chromosomal aberrations evoked in both males and females after ketalar administration. In these experiments, the applied dose for mouse was determined by the amount of dosage which was found to induce distinct symptoms of anaesthesia, recording (40 mg ketalarlkg b. wt.) per mouse. This dose was given either singly or in a double fashion (80 mg ketalar/kg b. wt.) to reveal the magnitude of toxic effects of such high dosing. Both doses were diluted with normal saline solution (0.9% NaCI), being injected intramuscularly in the experimented mice every other day. Either doses were left to act for 15, 30 and 45 days before their sacrifice. These experiments were have used 140 male and female adult albino Swiss mice; 70 males were assigned for the histological studies, whilst 35 males and 35 females were the target of the cytogenetical studies. For the histological purposes, mice were allocated into seven groups, ten mice each. The first one served as a control groups, the second, third and fourth groups were injected with (40 mg ketalar/kg b. wt.) for 15, 30 and 45 days respectively. The remaining three groups were given the high dosage of (80 mglkg b. wt.) ofketalar in the same manner.The specimens of the control and experimented testes stained with haematoxylin and eosin, beside Mallory’s triple stain preparations. In the cytogenetical part: For 35 assigned mice of either sex were classified as follows: 5 as control, 15 given (40 mglkg b. wt.) ofketalar and 15 animals injected with (80 mg ketalarlkg b. wt.). Those given either (40 or 80 mg/kg b. wt.) of ketalar were again divided into three subgroups (each of 5 mice) sacrifice after 15, 30 and 45 days. The statistical analysis of the data of chromosomal aberrations was carried out by employing the z- test. The results achieved from this investigation are thereafter briefly enumerated: External (morphological) symptoms: · Agitation, ataxia, tail erection, around encircling as well as respiratory impairment and convulsions were quite observable, followed by a period of lethargy. Such behavioural changes were both dose- and time- dependent. Histopathological results: The histopathological alterations of the testes ofketalar- treated Inice comprised mainly tubular atrophy, thickened peritubular tissue and variable degrees of degeneration (especially including hypoplasia and necrosis of the constituent germ cells) and tubular hyalinization, beside vacuolation and multinucleated gaint cells; particularly in the spermatocytes and spermatids stages. Also, the interstitial cells became vacuolated and hyperplastic. Vascular changes induced in these specilllens were denoted by hyperaemia, congestion and dilatation (vast) of the blood vessels. Such impairments had also occurred in a dose- and time- dependent manner. Cytogenetic results: The chromosomal complements of either normal male or female mice included 40 telocentric ones, comprising five groups; each consisting of chromosomes of nearly equal lengths. Ketalar treatment- at either 40 or 80 mg/kg b. wt.- had induced conspicuous structural and numerical chromosomal aberrations. The structural abnormalities consisted of deletions or fragments, breaks or gaps, ring chromosomes, centric fusion and radial configuration, beside beaded chromosomes, centromeric attenuation, stretching chromosomes as well as sticky chromosomes. The numerical aberrations were represented with polyploidy. The statistical analysis have indicated that the total frequencies of chromosomal aberrations were significantly increased by both elevated dosage and extended time of the drug action. Besides, another correlation was marked in this work pertaining mainly the centromeric attenuation aberration, which had recorded a higher frequency in ketalar- treated males than the correspondingly treated females, thus reflecting a sex- dependent relationship. In conclusion, it is quite convenient to stress the adverse effects of such drugs both histopathologically and cytogenetically, especially when human subjects are exposed to its action at high dose levels and/ or for prolonged periods or repeated manners. The latter avenue (i.e. cytogenetic impairments) indicates the mutagenic potentiality of this drug and the extension its injuries to the resultant offspring. Therefore, special consideration should be directed to the safety measures necessary in such prospects for the maintenance of proper health of human beings. |