[Buserelin inhibits apoptosis in male germ cells induced by busulfan in mouse testis]

The aim of this study was to investigate the effect of buserelin on apoptosis of male germ cells induced by busulfan in adult male mice. Male adult NMRI mice were divided into four group of eight each. Group 1 [control] administered PBS for 21 days subcutaneously, group 2 given 0.4 micro g buserelin for 21 days subcutaneously, group 3 given single dose of 30 mg/kg busulfan intraperitoneally and group 4 given both busulfan and buserelin for 21 days. The animals were sacrificed and their testes were dissected 35 days after the treatment. Evaluations were made by determining Johnson's score and apoptosis were assayed by terminal- deoxynucleotidyl- transferase-mediated dutp nick end labeling [TUNEL]. Statistical analyses were performed using ANOVA test. Recovery status and Johnson's score in group 4 were significantly higher than those of busulfan treated group 7.71 +/- 0.69 VS 4.46 +/- 0.56 [p< 0.001]. Apoptotic cells number cells were significantly more numerous in busulfan treated group than those of control 23.28 +/- 7.10 VS 3.54 +/- 1.02 [p<0.001]. While buserelin substantially reduced germ cell apoptosis in fourth group 10.50 +/- 2.91 in comparison with third group 23.28 +/- 7.10, [p<0.001]. Administration of buserelin after testicular damage by busulfan enhances the regeneration of spermatogenesis in mouse through inhibition of apoptosis in germ cells

[ morphologic and morphometric study of adult mouse testis following different doses of busulfan administration]

Anti-cancer drugs have adverse effects on spermatogenesis. Therefore, information on their role for the prevention of germinal epithelium destruction is necessary. The aim of this study was morphologic and morphometric evaluations of testes, measurement of volume and volume density of testes parameters, measurement of tubular diameters, germ and somatic cell counts following administration of different doses of busulfan in adult mice. In the present study, 42 male NMRI mice aged 6-8 weeks were used. The animals were divided into 5 groups. Case groups received a single dose of busulfan by intraperitoneal injection as 5, 10, 20 and 40 mg/kg in the first, second, third and forth groups respectively. The control group received only the solvent for busulfan. All the animals were killed 35 days after treatment and their testes were dissected out and processed for light microscope studies. Then morphometric studies were performed on testicular parameters. The data were analyzed using ANOVA and Tukey test and p values less than 0.05 were considered significant Busulfan administration in 5, 10, 20 and 40 mg/kg doses significantly reduced most morphometric parameters in testes with a maximum effect in the 40 mg/kg group. Volumes of testes, tubules and germinal epithelia were decreased significantly in the experiment groups [p<0.05] however, the volume of interstitial tissue increased [p<0.05]. Tubular diameters and thickness of epithelia were also decreased in the experiment groups. Number of germ cells was reduced, but number of sertoli cells was not affected. The number of leydig cells were not affected in 10 and 20 mg/kg busulfan treated groups, however in the 40 mg/kg treated group they were increased significantly [p<0.003]. In 5 mg/kg treated group there were no significant differences in morphologic and morphometric studies. Busulfan could reduce testicular parameters and disrupt spermatogenesis through affecting both germ and somatic cells in a dose dependent manner. Therefore, the side effects of busulfan on spermatogenesis should be considered during cancer therapies

Busulfán versus busulfán-interferón como terapia de mantenimiento en leucemia mieloide crónica / Busulfan versus busulfan-interferon as maintenance therapy in chronic myeloid leukemia

Se estudiaron 30 pacientes con el fin de evaluar la eficacia terapéutica y la toxicidad del interferón alfa-2b, asociado al busulfán, en el mantenimiento de la fase crónica con leucemia mieloide crónica de novo. Los pacientes recibieron busulfán hasta alcanzar la remisión hematológica completa, y se dividieron aleatoriamente en dos grupos: uno se mantuvo con busulfán el cual se administró cuando los leucocitos superaron los 5 x 10 9/L, y otro recibió interferón alfa a dosis de 5 millones UI SC tres veces por semana, agregándose busulfán cuando los leucocitos eran superiores a 15 x 10 9/L. El promedio de la duración de la fase crónica fue mayor en el grupo de busulfán-interferón, 31 vs 16 meses (p= 0.03) pero no hubo ningún caso de remisión citogenética. El interferón fue bien tolerado: ningún enfermo se eliminó por toxicidad del medicamento

Glutathione and glutathione-related enzymes in busulfan treated rat lens.

Glutathione (GSH) and GSH-related enzymes, glutathione reductase (GR), gamma-glutamyl cysteine synthetase (gamma-GCS), gamma-glutamyl transpeptidase (gamma-GTP), glutathione S-transferase (GST) and adenosine triphosphatase (ATPase) enzymes were analysed to study the effect of busulfan on the defence mechanisms of the lens. All these enzymes were found to increase significantly except GSH which showed only 7.9% increase as compared to controls in precataractous stage. These results affirm that busulfan is capable of evoking a response from the enzymes involved in the various pathways of GSH enabling the lens to prolong its clarity. The cataractous lenses showed significant decrease in all these parameters. Here, the impairment of the defense mechanism (GST, GR) and the total ATPase may be attributed to the cumulative action of the drug which can react with -SH groups of these enzymes, ultimately causing opacification.

A quantitative method for evaluating the effects of drugs on bone marrow cellularity using the same experimental animal: quantification of the effects of a single dose busulphan

Se describe un método que permite cuantificar la celuradidad de la médula ósea de la rata por unidad de peso. A tal efecto se determinaron en diferentes tiempos los números absolutos de cada tipo celular presentes en el fémur derecho e isquierdo del mismo animal de experimentación y los resultados se expresan en número de células por mg de médula ósea. En la rata normal se demostró que el número absoluto de cada tipo celular por mg de médula ósea es muy similar en el fémur derecho e izquierdo. Esto ocurre cuando el estudio de la celularidad medular se realiza simultáneamente en ambos huesos, y también cuando se comparan los resultados del estudio cuantitativo del fémur izquierdo con los del fémur derecho del mismo animal con 10 y 20 días de intervalo. Con el objeto de ratificar la validez del método para el estudio de la acción de drogas sobre la hematopoyesis medular, se observaron, además, los efectos de una dosis de busulfán (20 mg/Kg, vía oral), administrada inmediatamente después de que se realizó el estudio cuantitativo de la celularidad de la médula ósea del fémur izquierdo de una rata normal. Los resultados se compararon con los obtenidos de la médula ósea del fémur derecho de los mismos animales, 10 días después. Se demostró una marcada y significativa disminución del total de células nucleadas por mg de médula ósea, luego de ese período de observación. Los efectos celulares del busulfán fueron particularmente intensos sobre la progenie mieloide de médula ósea, con una reducción del