En el presente trabajo de investigación se determinó la actividad de la enzima UDPG deshidrogenasa en ratas tratadas crónicamente con cocaína por vía oral. Se prepararon para esto tres grupos de ratas, 1 control y 2 experimentales, las cuales consumieron diferentes dietas a base de caseína al 9%. Las dietas de los 2 grupos experimentales C7.5 y C15, a diferencia del grupo control que sólo contenía caseína, tenían diferentes concentraciones de cocaína de 7.5 mg/10g dieta y 15 mg/10 g dieta respectivamente. Las dietas fueron administradas ad libitum por un período de 22 días a los 3 grupos (n=7). Al término de este período los animales fueron decapitados, y se les extrajo el hígado, a partir del cual, se obtuvo la fracción sobrenadante 12000 g y la fracción citosólica por medio de centrifugación diferencial. Se utilizaron estas 2 fracciones subcelulares para la medición de la actividad de la UDPG deshidrogenasa y del contenido proteico. Los resultados muestran un incremento en la actividad de la UDPG deshidrogenasa en los grupos experimentales, el cual es directamente proporcional a la cantidad de cocaína consumida. Este aumento se produjo en ambas fracciones subcelulares. Los valores de micromoles de UDPGA/mg proteína formados en la fracción sobrenadante 12000 g fueron: Control, 5.49x10ˉ³ ± 5.69x10ˉ³; C7.5, 7.67x10ˉ³ ± 2.94x10ˉ³; y C15, 10.60 x10ˉ³ ± 3.35x10ˉ³. En el citosol los valores fueron: Control, 12.20 x10ˉ³ ± 4.13x10ˉ³; C7.5, 13.10 x10ˉ³ ± 3.77x10ˉ³; y C15, 14.80x10ˉ³ ± 3.93x10ˉ³. Además, se obtuvo mayor contenido proteico en ambas fracciones subcelulares en los grupos experimentales y disminución del peso corporal producido por la cocaína. Estos hallazgos sugieren que el incremento en la actividad de la UDPG deshidrogenasa se debería a que la cocaína induce la síntesis de esta enzima produciendo así UDPGA, el cual sería utilizado para la conjugación y excreción de los metabolitos producidos a partir de la biotransformación de la cocaína en el organismo. / In the present investigation work the activity of the enzyme UDPG dehydrogenase was determined in chronically cocaine-treated rats utilizing the oral route. To approach this three groups of rats were prepared, 1 control and 2 experimental, all three consuming different casein 9%-based diets. The diets of the 2 experimental groups C7.5 and C15, unlike of the control group that only contained casein, had different cocaine concentrations of 7.5 mg/10g diet and 15 mg/10g diet respectively. All diets were fed ad libitum for a period of 22 days to the three groups (n=7). Ending this period the animals were decapitated and the liver was removed, from which, the supernatant 12000 g fraction and the cytosolic fraction were obtained through differential centrifugation. These two subcellular fractions were used to measure the UDPG dehydrogenase activity, as well as their respective protein content. The results showed increased UDPG dehydrogenase activity in the experimental groups, which is directly proportional to the amount of cocaine consumed. This increasing in activity occurred in both subcellular fractions. The values of micromoles of UDPGA/mg protein formed in the supernatant 12000 g fraction were: Control, 5.49x10ˉ³ ± 5.69x10ˉ³; C7.5, 7.67x10ˉ³ ± 2.94x10ˉ³; and C15, 10.60 x10ˉ³ ± 3.35x10ˉ³. In the cytosol the values were: Control, 12.20 x10ˉ³ ± 4.13x10ˉ³; C7.5, 13.10 x10ˉ³ ± 3.77x10ˉ³; and C15, 14.80 x10ˉ³ ± 3.93x10ˉ³. Moreover, a major protein content in both subcellular fractions of the experimental groups was obtained and also a lowering in the body weight by the action of cocaine. These findings suggest that the increased UDPG dehydrogenase activity would be due to the induction of this enzyme synthesis, therefore producing UDPGA, which would be used for the conjugation and excretion of the cocaine metabolites resulting from its biotransformation in the body.

En el presente trabajo de investigación se determinó la actividad de la enzima UDPG deshidrogenasa en ratas tratadas crónicamente con cocaína por vía oral. Se prepararon para esto tres grupos de ratas, 1 control y 2 experimentales, las cuales consumieron diferentes dietas a base de caseína al 9%. Las dietas de los 2 grupos experimentales C7.5 y C15, a diferencia del grupo control que sólo contenía caseína, tenían diferentes concentraciones de cocaína de 7.5 mg/10g dieta y 15 mg/10 g dieta respectivamente. Las dietas fueron administradas ad libitum por un período de 22 días a los 3 grupos (n=7). Al término de este período los animales fueron decapitados, y se les extrajo el hígado, a partir del cual, se obtuvo la fracción sobrenadante 12000 g y la fracción citosólica por medio de centrifugación diferencial. Se utilizaron estas 2 fracciones subcelulares para la medición de la actividad de la UDPG deshidrogenasa y del contenido proteico. Los resultados muestran un incremento en la actividad de la UDPG deshidrogenasa en los grupos experimentales, el cual es directamente proporcional a la cantidad de cocaína consumida. Este aumento se produjo en ambas fracciones subcelulares. Los valores de micromoles de UDPGA/mg proteína formados en la fracción sobrenadante 12000 g fueron: Control, 5.49x10ˉ³ ± 5.69x10ˉ³; C7.5, 7.67x10ˉ³ ± 2.94x10ˉ³; y C15, 10.60 x10ˉ³ ± 3.35x10ˉ³. En el citosol los valores fueron: Control, 12.20 x10ˉ³ ± 4.13x10ˉ³; C7.5, 13.10 x10ˉ³ ± 3.77x10ˉ³; y C15, 14.80x10ˉ³ ± 3.93x10ˉ³. Además, se obtuvo mayor contenido proteico en ambas fracciones subcelulares en los grupos experimentales y disminución del peso corporal producido por la cocaína. Estos hallazgos sugieren que el incremento en la actividad de la UDPG deshidrogenasa se debería a que la cocaína induce la síntesis de esta enzima produciendo así UDPGA, el cual sería utilizado para la conjugación y excreción de los metabolitos producidos a partir de la biotransformación de la cocaína en el organismo. / In the present investigation work the activity of the enzyme UDPG dehydrogenase was determined in chronically cocaine-treated rats utilizing the oral route. To approach this three groups of rats were prepared, 1 control and 2 experimental, all three consuming different casein 9%-based diets. The diets of the 2 experimental groups C7.5 and C15, unlike of the control group that only contained casein, had different cocaine concentrations of 7.5 mg/10g diet and 15 mg/10g diet respectively. All diets were fed ad libitum for a period of 22 days to the three groups (n=7). Ending this period the animals were decapitated and the liver was removed, from which, the supernatant 12000 g fraction and the cytosolic fraction were obtained through differential centrifugation. These two subcellular fractions were used to measure the UDPG dehydrogenase activity, as well as their respective protein content. The results showed increased UDPG dehydrogenase activity in the experimental groups, which is directly proportional to the amount of cocaine consumed. This increasing in activity occurred in both subcellular fractions. The values of micromoles of UDPGA/mg protein formed in the supernatant 12000 g fraction were: Control, 5.49x10ˉ³ ± 5.69x10ˉ³; C7.5, 7.67x10ˉ³ ± 2.94x10ˉ³; and C15, 10.60 x10ˉ³ ± 3.35x10ˉ³. In the cytosol the values were: Control, 12.20 x10ˉ³ ± 4.13x10ˉ³; C7.5, 13.10 x10ˉ³ ± 3.77x10ˉ³; and C15, 14.80 x10ˉ³ ± 3.93x10ˉ³. Moreover, a major protein content in both subcellular fractions of the experimental groups was obtained and also a lowering in the body weight by the action of cocaine. These findings suggest that the increased UDPG dehydrogenase activity would be due to the induction of this enzyme synthesis, therefore producing UDPGA, which would be used for the conjugation and excretion of the cocaine metabolites resulting from its biotransformation in the body. / Tesis

As mortes por causas externas e o consumo de drogas são problemas crescentes nos grandes centros urbanos. No estudo foi investigado se estes fatores, também afrontam cidades de médio e pequeno porte da região Bragantina. Foram realizadas análises toxicológicas para verificar a exposição à cocaína, em amostras de cabelo e urina de indivíduos vítimas de morte violenta (n=42), submetidos à necropsia no Instituto Médico Legal de Bragança Paulista. Do total de indivíduos submetidos ao estudo, 14% apresentaram resultados positivos para cocaína. Foi possível verificar que 38% das vítimas de homicídios eram usuários de cocaína. O perfil sociodemográfico dos indivíduos vítimas de morte violenta foi: sexo masculino, branco, solteiro, faixa etária de 21-30 anos e empregados. No estudo foi constatada exposição à cocaína entre vítimas de mortes violentas ocorridas na Região Bragantina. / The deaths for externaI causes and the consumption of drugs are increasing problems in the great urban centers. In the study it was investigated if these factors also confront medium and small cities of Bragantina region. Toxicological analyses had been carried through to verify the exposure to the cocaine, in samples of hair and urine of individuaIs victims of violent death (n=42), submitted to the autopsy in the Legal Medical Institute of Bragança Paulista. Of the total of individuaIs submitted to the study, 14% had presented positive results for cocaine. It was possible to verify that 38% of homicides victims were cocaine users. The sociodemographic profile of the individuaIs victims of violent death was: male sex, white, single, 21-30 years age group and employees. In the study, exposure to the cocaine between victims of violent deaths occurred in the Bragantina Region was evidenced.

As mortes por causas externas e o consumo de drogas são problemas crescentes nos grandes centros urbanos. No estudo foi investigado se estes fatores, também afrontam cidades de médio e pequeno porte da região Bragantina. Foram realizadas análises toxicológicas para verificar a exposição à cocaína, em amostras de cabelo e urina de indivíduos vítimas de morte violenta (n=42), submetidos à necropsia no Instituto Médico Legal de Bragança Paulista. Do total de indivíduos submetidos ao estudo, 14% apresentaram resultados positivos para cocaína. Foi possível verificar que 38% das vítimas de homicídios eram usuários de cocaína. O perfil sociodemográfico dos indivíduos vítimas de morte violenta foi: sexo masculino, branco, solteiro, faixa etária de 21-30 anos e empregados. No estudo foi constatada exposição à cocaína entre vítimas de mortes violentas ocorridas na Região Bragantina. / The deaths for externaI causes and the consumption of drugs are increasing problems in the great urban centers. In the study it was investigated if these factors also confront medium and small cities of Bragantina region. Toxicological analyses had been carried through to verify the exposure to the cocaine, in samples of hair and urine of individuaIs victims of violent death (n=42), submitted to the autopsy in the Legal Medical Institute of Bragança Paulista. Of the total of individuaIs submitted to the study, 14% had presented positive results for cocaine. It was possible to verify that 38% of homicides victims were cocaine users. The sociodemographic profile of the individuaIs victims of violent death was: male sex, white, single, 21-30 years age group and employees. In the study, exposure to the cocaine between victims of violent deaths occurred in the Bragantina Region was evidenced.